Chimeric compounds for targeted degradation of androgen receptor protein, methods for their preparation and pharmaceutical uses

Abstract

The present invention relates to chimeric compounds for targeted degradation of androgen receptor protein, their preparation method and pharmaceutical use thereof. Specifically, the present invention relates to spirocyclic compounds represented by general formula (I), their preparation method and pharmaceutical composition comprising said spirocyclic compounds, and their use as therapeutic agents, in particular as androgen receptor degraders, and in the preparation of medicaments for treating and / or preventing androgen receptor-mediated or -dependent diseases or conditions. TIFF2024543129000406.tif1655

Description

[Technical field]

[0001] The present disclosure belongs to the pharmaceutical field and relates to novel proteolysis targeted chimeric (PROTAC) compounds, their preparation methods and their pharmaceutical uses.Specifically, the present disclosure relates to spirocyclic compounds represented by general formula (I), their preparation methods and pharmaceutical compositions comprising said spirocyclic compounds, and their use as therapeutic agents, in particular as androgen receptor degraders, and in the preparation of medicaments for treating and / or preventing androgen receptor-mediated or -dependent diseases or conditions. [Background technology]

[0002] PROTAC (PROteolysis TArgeting Chimera) is a heterozygous bifunctional small molecule. Its structure contains two different ligands, a ubiquitin ligase E3 ligand and a ligand that binds to a target protein, and the two ligands are linked by a linking unit. PROTAC forms a target protein-PROTAC-E3 ternary complex by bringing the target protein and ubiquitin ligase E3 in the cell into close proximity, and then the E3 ubiquitin ligase attaches a ubiquitin protein tag to the target protein, which then initiates a powerful ubiquitination-proteasome system in the cell, specifically degrading the target protein and achieving an inhibitory effect on the corresponding protein signaling pathway (Cell Biochem Funct. 2019, 37, 21-30). Compared with traditional small molecule inhibitors, PROTACs have unique advantages: 1) PROTACs do not require long-term and strong binding to the target protein, and the degradation process of the target protein is similar to a catalytic reaction. By periodically binding and degrading the target protein, the systemic exposure of the drug can be reduced and the occurrence of toxicity and side effects can be reduced; 2) After the target protein is degraded, it must be resynthesized to restore its function. Therefore, degradation of the target protein has a more effective and long-lasting antitumor effect than inhibition of its activity, and does not cause drug resistance due to mutations in the target protein; 3) PROTACs have the potential to treat targets that are currently thought to be undruggable, such as transcription factors, scaffolding proteins, and regulatory proteins.

[0003] The process of discovery about CRBN-type E3 ligase ligands is related to the study of the mechanism of action of thalidomide. In 2010, scientists discovered that cereblon is one of the binding proteins of thalidomide during the study of thalidomide toxicity (Science 2010,327,1345). Cereblon is part of the E3 ubiquitin ligase protein complex and acts selectively on ubiquitinated proteins as a substrate receptor. The study revealed that thalidomide-cereblon binding in vivo can lead to the teratogenicity of thalidomide. Subsequent studies showed that the compound and related structures can be used as anti-inflammatory, anti-angiogenic and anti-cancer drugs, and lenalidomide and pomalidomide obtained by further modification of the structure of thalidomide have significantly improved safety and clearly reduced teratogenic effects, and lenalidomide was approved for sale by the FDA in 2006. Two pioneering papers published in Science in 2014 disclosed that lenalidomide works by degrading two specific B cell transcription factors, Ikaros family zinc finger structural proteins 1 and 3 (IKZF1 and IKZF3), further indicating that thalidomide's structure may further act in target protein degradation by binding to the cereblon E3 ubiquitin ligase protein complex (Science, 2014, 343, 301; Science, 2014, 343, 305).

[0004] The androgen receptor (AR) is a ligand-dependent reverse transcription regulatory protein that belongs to the nuclear receptor superfamily and is mainly present in the cell nucleus. When unliganded, AR binds to heat shock proteins (HSPs), and when AR binds to a ligand, it changes its conformation, dissociates from HSPs, and has a high affinity for DNA (activated AR). Activated AR binds to a specific DNA sequence in the cell nucleus in a dimeric form - the androgen response element (ARE) - and interacts with other transcription factors to regulate the expression of related genes and produce biological effects. Research has shown that abnormalities in the AR signaling pathway are closely related to the occurrence and progression of diseases such as prostate cancer, benign prostatic hyperplasia, Kennedy's disease, male infertility, androgen insensitivity syndrome, and male breast cancer.

[0005] Prostate cancer is one of the most common malignant tumors. According to statistics, in 2018, there were nearly 1.3 million new cases and 359,000 deaths worldwide, accounting for 13.5% of the incidence of malignant tumors in men, the second highest, and 6.7% of the mortality rate of malignant tumors in men, the fifth highest. Several AR antagonists have already obtained marketing approval and have been successfully used in the treatment of castration-resistant prostate cancer, becoming the main means of treating prostate cancer. However, many patients develop drug resistance after 0.5 to 2 years of treatment, leading to the progression of the disease. In some drug-resistant patients, the growth of cancer cells still depends on the AR signaling pathway.

[0006] More effective means of treating prostate cancer must be developed. Unlike AR antagonists, PROTACs can degrade AR and more effectively inhibit the AR signaling pathway, which may be a promising method of treating prostate cancer. The patent applications disclosed for AR protein targeting PROTAC compounds include WO2015160845A2, WO2016197032A1, US2015291562A1, WO2018071606A1, WO2019023553A1, WO2016118666A1, WO2018144649A1, WO2020142228A1, WO2020198711A1, WO2021061644A1 and WO2021055756A1. Summary of the Invention

[0007] The present disclosure aims to provide a compound represented by general formula (I) or a medicamentable salt thereof: [ka] Among them, R is an aryl group or a heteroaryl group, wherein the aryl group and the heteroaryl group are each independently optionally selected from halogen, alkyl group, alkoxy group, haloalkyl group, haloalkoxy group, cyano group, -(CH 2 ) n NR a R b , nitro group, hydroxy group, hydroxyalkyl group, aminoalkyl group, alkoxyalkyl group, cycloalkylalkyl group, heterocyclylalkyl group, cycloalkyl group, heterocyclyl group, aryl group, and heteroaryl group, A is, [ka] Selected from [ka] is a single bond or a double bond, Q 1 , Q2 , Q 3 , Q 4 and Q 5 one of the groups is a carbon atom, and the remaining four groups are the same or different and each independently is a nitrogen atom or CR′; Each R' may be the same or different and independently represent a hydrogen atom, a halogen, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cyano group, a hydroxy group, a nitro group, or -(CH 2 ) n NR c R d Selected from R 1 is selected from a hydrogen atom, an alkyl group, a haloalkyl group, a hydroxyalkyl group, an aminoalkyl group, and an alkoxyalkyl group; R 2 is selected from a hydrogen atom, a halogen, an alkyl group, a haloalkyl group, a hydroxyalkyl group, an alkoxy group, a haloalkoxy group, a hydroxy group, a cyano group, an aminoalkyl group, and an alkoxyalkyl group; X 1 is a spiro ring group, wherein the spiro ring group is optionally selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, cyano, nitro, hydroxy, hydroxyalkyl, aminoalkyl, alkoxyalkyl, cycloalkylalkyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 3 , -C(O)R 3 , -C(O)OR 3 , -S(O) m R 3 , -NR 4 R 5 , -C(O)NR 4 R 5 , -S(O) m NR 4 R 5 , ═O and ═S; X 2 -C(O)-, -S(O) 2 -and-(CR2a R 2b ) m1 -Selected from X 3 is selected from a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group, wherein the cycloalkyl group, the heterocyclyl group, the aryl group, and the heteroaryl group are each independently optionally selected from a halogen, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a cyano group, -(CH 2 ) n NR e R f , a nitro group, a hydroxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, and =O, X 4 Ha-J 1 -J 2 -J 3 -J 4 -J 5 -Of which, J 1 isX 3 is connected to J 1 -O-, -S-, -NR 6 -, -C(O)-, -S(O) 2 -, -(CR 7 R 8 ) m2 -, an alkenyl group, and an alkynyl group; J 2 is a cycloalkyl group or a heterocyclyl group, wherein the cycloalkyl group and the heterocyclyl group are each independently optionally selected from halogen, alkyl group, alkoxy group, haloalkyl group, haloalkoxy group, cyano group, -(CH 2 ) n NR g R h, a nitro group, a hydroxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, and =O, J 3 -O-, -S-, -NR 6a -, -C(O)-, -S(O) 2 -, -(CR 7a R 8a ) m3 -, alkenyl, alkynyl, cycloalkyl and heterocyclyl groups, wherein the cycloalkyl and heterocyclyl groups are each independently optionally selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, cyano, -(CH 2 ) n NR g R h , a nitro group, a hydroxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, and =O, J 4 is selected from a bond, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group, wherein the cycloalkyl group, the heterocyclyl group, the aryl group, and the heteroaryl group are each independently optionally selected from a halogen, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a cyano group, -(CH 2 ) n NR g R h , a nitro group, a hydroxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, and =O, J 5 is -C(O)NR 6b -, -NR 6bC(O)-, -O-, -S-, -NR 6b -, -C(O)-, -S(O) 2 -, -(CR 7b R 8b ) m4 -, alkenyl, alkynyl, cycloalkyl and heterocyclyl groups, wherein the cycloalkyl and heterocyclyl groups are each independently optionally selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, cyano, -(CH 2 ) n NR g R h , a nitro group, a hydroxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, and =O, R a , R b , R c , R d , R e , R f , R g , R h , R 6 , R 6a and R 6b are the same or different and each independently selected from a hydrogen atom, an alkyl group, a haloalkyl group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, and a heterocyclylalkyl group, R 2a , R 2b , R 7 , R 8 , R 7a , R 8a , R 7b and R 8b are the same or different and each independently selected from a hydrogen atom, a halogen, an alkyl group, an alkoxy group, a hydroxy group, an amino group, a cyano group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, and a heterocyclylalkyl group; R 3are selected from a hydrogen atom, an alkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group and a heteroaryl group, wherein the alkyl group, the cycloalkyl group, the heterocyclyl group, the aryl group and the heteroaryl group are each independently optionally substituted with one or more substituents selected from a halogen, an alkyl group, an alkoxy group, a hydroxy group, an amino group, a cyano group, a nitro group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, =O, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group and a heteroaryl group; R 4 and R 5 are the same or different and each independently selected from a hydrogen atom, an alkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group and a heteroaryl group, wherein the alkyl group, the cycloalkyl group, the heterocyclyl group, the aryl group and the heteroaryl group are each independently optionally substituted with one or more substituents selected from a halogen, an alkyl group, an alkoxy group, a hydroxy group, an amino group, a cyano group, a nitro group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, =O, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group and a heteroaryl group; Or R 4 and R 5 together with the nitrogen atom to which it is linked form a heterocyclyl group, which is optionally substituted with one or more substituents selected from halogen, alkyl, alkoxy, hydroxy, amino, cyano, nitro, haloalkyl, haloalkoxy, hydroxyalkyl, =O, aminoalkyl, alkoxyalkyl, cycloalkylalkyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl; n is 0, 1, 2 or 3; m is 0, 1 or 2; m1 is 0, 1, 2 or 3; m2 is 0, 1, 2 or 3; m3 is 0, 1, 2 or 3; and m4 is 0, 1, 2 or 3.

[0008] In some embodiments of the present disclosure, there is provided a compound represented by the above general formula (I) or a medicamentable salt thereof, wherein: R is an aryl group or a heteroaryl group, wherein the aryl group and the heteroaryl group are each independently optionally selected from halogen, alkyl group, alkoxy group, haloalkyl group, haloalkoxy group, cyano group, -(CH 2 ) n NR a R b , nitro group, hydroxy group, hydroxyalkyl group, aminoalkyl group, alkoxyalkyl group, cycloalkylalkyl group, heterocyclylalkyl group, cycloalkyl group, heterocyclyl group, aryl group, and heteroaryl group, A is, [ka] Selected from [ka] is a single bond or a double bond, Q 1 , Q 2 , Q 3 , Q 4 and Q 5 one of the groups is a carbon atom, and the remaining four groups are the same or different and each independently is a nitrogen atom or CR′; Each R' may be the same or different and independently represent a hydrogen atom, a halogen, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cyano group, a hydroxy group, a nitro group, or -(CH 2 ) n NR c R d Selected from R 1is selected from a hydrogen atom, an alkyl group, a haloalkyl group, a hydroxyalkyl group, an aminoalkyl group, and an alkoxyalkyl group; R 2 is selected from a hydrogen atom, a halogen, an alkyl group, a haloalkyl group, a hydroxyalkyl group, an alkoxy group, a haloalkoxy group, a hydroxy group, a cyano group, an aminoalkyl group, and an alkoxyalkyl group; X 1 is a spiro ring group, wherein the spiro ring group is optionally selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, cyano, nitro, hydroxy, hydroxyalkyl, aminoalkyl, alkoxyalkyl, cycloalkylalkyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 3 , -C(O)R 3 , -C(O)OR 3 , -S(O) m R 3 , -NR 4 R 5 , -C(O)NR 4 R 5 , -S(O) m NR 4 R 5 , ═O and ═S; X 2 -C(O)-, -S(O) 2 -and-(CR 2a R 2b ) m1 -Selected from X 3 is selected from a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group, wherein the cycloalkyl group, the heterocyclyl group, the aryl group, and the heteroaryl group are each independently optionally selected from a halogen, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a cyano group, -(CH 2 ) n NR e R f, a nitro group, a hydroxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, and =O, X 4 Ha-J 1 -J 2 -J 3 -J 4 -J 5 -Of which, J 1 isX 3 is connected to J 1 -O-, -S-, -NR 6 -, -C(O)-, -S(O) 2 -, -(CR 7 R 8 ) m2 -, an alkenyl group, and an alkynyl group; J 2 is a cycloalkyl group or a heterocyclyl group, wherein the cycloalkyl group and the heterocyclyl group are each independently optionally selected from halogen, alkyl group, alkoxy group, haloalkyl group, haloalkoxy group, cyano group, -(CH 2 ) n NR g R h , a nitro group, a hydroxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, and =O, J 3 -O-, -S-, -NR 6a -, -C(O)-, -S(O) 2 -, -(CR 7a R 8a ) m3 -, alkenyl, alkynyl, cycloalkyl and heterocyclyl groups, wherein the cycloalkyl and heterocyclyl groups are each independently optionally selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, cyano, -(CH2 ) n NR g R h , a nitro group, a hydroxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, and =O, J 4 is selected from a bond, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group, wherein the cycloalkyl group, the heterocyclyl group, the aryl group, and the heteroaryl group are each independently optionally selected from a halogen, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a cyano group, -(CH 2 ) n NR g R h , a nitro group, a hydroxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, and =O, J 5 is -C(O)NR 6b -, -NR 6b C(O)-, -O-, -S-, -NR 6b -, -C(O)-, -S(O) 2 -, -(CR 7b R 8b ) m4 -, alkenyl, alkynyl, cycloalkyl and heterocyclyl groups, wherein the cycloalkyl and heterocyclyl groups are each independently optionally selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, cyano, -(CH 2 ) n NR g R h, a nitro group, a hydroxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, and =O, R a , R b , R c , R d , R e , R f , R g , R h , R 6 , R 6a and R 6b are the same or different and each independently selected from a hydrogen atom, an alkyl group, a haloalkyl group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, and a heterocyclylalkyl group, R 2a , R 2b , R 7 , R 8 , R 7a , R 8a , R 7b and R 8b are the same or different and each independently selected from a hydrogen atom, a halogen, an alkyl group, an alkoxy group, a hydroxy group, an amino group, a cyano group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, and a heterocyclylalkyl group; R 3 are selected from a hydrogen atom, an alkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group and a heteroaryl group, wherein the alkyl group, the cycloalkyl group, the heterocyclyl group, the aryl group and the heteroaryl group are each independently optionally substituted with one or more substituents selected from a halogen, an alkyl group, an alkoxy group, a hydroxy group, an amino group, a cyano group, a nitro group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, =O, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group and a heteroaryl group; R 4 and R 5 are the same or different and each independently selected from a hydrogen atom, an alkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group and a heteroaryl group, wherein the alkyl group, the cycloalkyl group, the heterocyclyl group, the aryl group and the heteroaryl group are each independently optionally substituted with one or more substituents selected from a halogen, an alkyl group, an alkoxy group, a hydroxy group, an amino group, a cyano group, a nitro group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, =O, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group and a heteroaryl group; Or R 4 and R 5 together with the nitrogen atom to which it is linked form a heterocyclyl group, which is optionally substituted with one or more substituents selected from halogen, alkyl, alkoxy, hydroxy, amino, cyano, nitro, haloalkyl, haloalkoxy, hydroxyalkyl, =O, aminoalkyl, alkoxyalkyl, cycloalkylalkyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl; n is 0, 1, 2 or 3; m is 0, 1 or 2; m1 is 0, 1, 2 or 3; m2 is 0, 1, 2 or 3; m3 is 0, 1, 2 or 3; and m4 is 0, 1, 2 or 3.

[0009] In some embodiments of the present disclosure, there is provided a compound represented by the above general formula (I) or a medicamentable salt thereof, wherein R is a 6- to 10-membered aryl group or a 5- to 10-membered heteroaryl group, wherein the 6- to 10-membered aryl group and the 5- to 10-membered heteroaryl group are each independently optionally selected from halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, -(CH 2 ) n NR a R b , nitro group, hydroxy group, C 1-6 Hydroxyalkyl group, C 1-6 Aminoalkyl groups, C 1-6 Alkoxy C 1-6 Alkyl group, 3-8 membered cycloalkyl group 1-6 Alkyl group, 3-8 membered heterocyclyl C 1-6 substituted with one or more substituents selected from an alkyl group, a 3- to 8-membered cycloalkyl group, and a 3- to 8-membered heterocyclyl group; R a and R b are the same or different and each independently represent a hydrogen atom or C 1-6 is an alkyl group, n is 0, 1, 2 or 3; Preferably, R is a phenyl group or a 5- or 6-membered heteroaryl group, wherein the phenyl group and the 5- or 6-membered heteroaryl group are each independently optionally selected from halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, cyano group, amino group, nitro group, hydroxy group and C 1-6 substituted with one or more substituents selected from hydroxyalkyl groups; Preferably, R is a phenyl group, which optionally contains halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 substituted with one or more substituents selected from haloalkyl groups and cyano groups; More preferably, R is a phenyl group, wherein said phenyl group is optionally substituted with one or more substituents selected from halogen and cyano groups; Most preferably, R is a phenyl group, said phenyl group being optionally substituted with one or more substituents selected from chlorine atoms and cyano groups.

[0010] In some embodiments of the present disclosure, there is provided a compound represented by the above general formula (I) or a medicamentable salt thereof, wherein R is [ka] and Z 1 is N or CR 3b and Z 2 is N or CR 3c and R 3a , R 3b and R 3c are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, cyano group, amino group, nitro group, hydroxy group and C 1-6 hydroxyalkyl groups, preferably R is [ka] More preferably, R is selected from [ka] It is.

[0011] In some embodiments of the present disclosure, there is provided a compound represented by the above general formula (I) or a medicamentable salt thereof, wherein X 1 is a 6- to 14-membered spiroheterocyclyl group, wherein the 6- to 14-membered spiroheterocyclyl group optionally contains halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, cyano group, nitro group, hydroxy group, C 1-6 Hydroxyalkyl group, C 1-6 Aminoalkyl groups, C 1-6 Alkoxy C 1-6 Alkyl group, 3-8 membered cycloalkyl group 1-6 Alkyl group, 3-8 membered heterocyclyl C 1-6Alkyl group, 3- to 8-membered cycloalkyl group, 3- to 8-membered heterocyclyl group, 6- to 10-membered aryl group, 5- to 10-membered heteroaryl group, -NR 4 R 5 , ═O and ═S; R 4 and R 5 are the same or different and each independently represent a hydrogen atom or C 1-6 It is an alkyl group.

[0012] In some embodiments of the present disclosure, there is provided a compound represented by the above general formula (I) or a medicamentable salt thereof, wherein X 1 teeth [ka] and Bonds marked with * are X 2 is connected to G 1 is N or CH, G 2 is N or CH, R 1a , R 1b , R 1c , R 1d and R 1e are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, cyano group, hydroxy group, C 1-6 Hydroxyalkyl group, C 1-6 Aminoalkyl groups, C 1-6 Alkoxy C 1-6 Alkyl group, 3-8 membered cycloalkyl group 1-6 Alkyl group, 3-8 membered heterocyclyl C 1-6 Alkyl groups, 3- to 8-membered cycloalkyl groups, and -NR 4 R 5 Selected from Or R 1a and R 1bforms a 3- to 8-membered cycloalkyl group or a 3- to 8-membered heterocyclyl group together with the carbon atom to which it is linked, and the 3- to 8-membered cycloalkyl group and the 3- to 8-membered heterocyclyl group are each independently optionally selected from halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, cyano group, hydroxy group, C 1-6 Hydroxyalkyl group, C 1-6 Aminoalkyl groups, C 1-6 Alkoxy C 1-6 Alkyl group, 3-8 membered cycloalkyl group 1-6 Alkyl group, 3-8 membered heterocyclyl C 1-6 Alkyl groups, 3-8 membered cycloalkyl groups, -NR 4 R 5 and ═O; Or R 1c and R 1d forms a 3- to 8-membered cycloalkyl group or a 3- to 8-membered heterocyclyl group together with the carbon atom to which it is linked, and the 3- to 8-membered cycloalkyl group and the 3- to 8-membered heterocyclyl group are each independently optionally selected from halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, cyano group, hydroxy group, C 1-6 Hydroxyalkyl group, C 1-6 Aminoalkyl groups, C 1-6 Alkoxy C 1-6 Alkyl group, 3-8 membered cycloalkyl group 1-6 Alkyl group, 3-8 membered heterocyclyl C 1-6 Alkyl groups, 3-8 membered cycloalkyl groups, -NR 4 R 5 and ═O; Or R 1a and R 1b forms C=O together with the carbon atom to which it is attached, Or R 1c and R 1dforms C=O together with the carbon atom to which it is attached, R 4 and R 5 are the same or different and each independently represent a hydrogen atom or C 1-6 is an alkyl group, o is 0 or 1; p is 0 or 1; q is 0, 1, 2 or 3; r is 0, 1, 2 or 3; s is 0, 1, 2, 3 or 4; t is 0, 1, 2, 3, or 4, and j is 0, 1, 2, 3 or 4.

[0013] In some embodiments of the present disclosure, there is provided a compound represented by the above general formula (I) or a medicamentable salt thereof, wherein X 1 teeth [ka] and bonds marked with * are X 2 is connected to R 1a , R 1b , R 1c and R 1d are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, Or R 1a and R 1b forms C=O together with the carbon atom to which it is attached, Or R 1c and R 1d forms C=O together with the carbon atom to which it is attached, q is 0, 1, 2 or 3; r is 0, 1, 2 or 3; s is 0, 1, 2, 3 or 4; and t is 0, 1, 2, 3 or 4.

[0014] In some embodiments of the present disclosure, there is provided a compound represented by the above general formula (I) or a medicamentable salt thereof, wherein X 1 teeth [ka] and bonds marked with * are X 2 is connected to R 1a and R 1b are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, or R 1a and R 1b forms C=O together with the carbon atom to which it is attached.

[0015] In some embodiments of the present disclosure, there is provided a compound represented by the above general formula (I) or a medicamentable salt thereof, wherein X 1 teeth [ka] and bonds marked with * are X 2 is connected to R 1a is a hydrogen atom, halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl group, preferably a hydrogen atom or C 1-6 is an alkyl group, more preferably C 1-6 It is preferably an alkyl group, and more preferably a methyl group.

[0016] In some embodiments of the present disclosure, there is provided a compound represented by the above general formula (I) or a medicamentable salt thereof, wherein X 1 teeth [ka] and bonds marked with * are X 2 is connected to R 1c and R 1d are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, or R 1c and R 1d forms C=O together with the carbon atom to which it is attached.

[0017] In some embodiments of the present disclosure, there is provided a compound represented by the above general formula (I) or a medicamentable salt thereof, wherein X 1 teeth [ka] and bonds marked with * are X 2 is connected to R 1c is a hydrogen atom, halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, preferably C 1-6 It is an alkyl group, and more preferably a methyl group.

[0018] In some embodiments of the present disclosure, there is provided a compound represented by the above general formula (I) or a medicamentable salt thereof, wherein X 1 teeth [ka] Preferably, X 1 teeth [ka] More preferably, X 1 teeth [ka] and most preferably, X 1 teeth [ka] and bonds marked with * are X 2 is linked to.

[0019] In some embodiments of the present disclosure, the compound represented by the above general formula (I) or a medicamentable salt thereof is a compound represented by the general formula (II) or a medicamentable salt thereof: [ka] Among them, R 1a is a hydrogen atom, halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, preferably R 1a is C 1-6 More preferably, R 1a is a methyl group, Z 1 is N or CR 3b and Z 2 is N or CR 3c and R 3a , R 3b and R 3c are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, cyano group, amino group, nitro group, hydroxy group and C 1-6 hydroxyalkyl groups, and X 2 , X3 , X 4 and A is as defined in general formula (I).

[0020] In some embodiments of the present disclosure, the compound represented by the above general formula (I) and general formula (II) or a medicamentable salt thereof is a compound represented by general formula (II-1) or a medicamentable salt thereof: [ka] Among them, R 1a is a halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, preferably R 1a is C 1-6 More preferably, R 1a is a methyl group, and Z 1 , Z 2 , R 3a , X 2 , X 3 , X 4 and A is as defined in general formula (II).

[0021] In some embodiments of the present disclosure, the compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein X 3 is a 6- to 10-membered aryl group or a 5- to 10-membered heteroaryl group, wherein the 6- to 10-membered aryl group and the 5- to 10-membered heteroaryl group are each independently optionally selected from halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, -(CH 2 ) n NR e R f , nitro group, hydroxy group, C1-6 Hydroxyalkyl group, C 1-6 Aminoalkyl groups, C 1-6 Alkoxy C 1-6 Alkyl group, 3-8 membered cycloalkyl group 1-6 Alkyl group, 3-8 membered heterocyclyl C 1-6 substituted with one or more substituents selected from an alkyl group, a 3- to 8-membered cycloalkyl group, a 3- to 8-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; R e and R f are the same or different and each independently represent a hydrogen atom or C 1-6 an alkyl group and n is 0, 1, 2 or 3; Preferably, X 3 is a 6- to 10-membered aryl group or a 5- to 10-membered heteroaryl group, wherein the 6- to 10-membered aryl group and the 5- to 10-membered heteroaryl group are each independently optionally selected from halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 substituted with one or more substituents selected from hydroxyalkyl groups; More preferably, X 3 is selected from a phenyl group, a pyridyl group, a pyrimidinyl group, a pyridazinyl group and a pyrazinyl group, wherein the phenyl group, the pyridyl group, the pyrimidinyl group, the pyridazinyl group and the pyrazinyl group are each independently optionally selected from halogen, C 1-6 Alkyl group and C 1-6 substituted with one or more substituents selected from haloalkyl groups; Most preferably, X 3 is a phenyl group or a pyridyl group, wherein the phenyl group and the pyridyl group are each independently optionally selected from halogen, C 1-6 Alkyl group and C 1-6 It is substituted with one or more substituents selected from haloalkyl groups.

[0022] In some embodiments of the present disclosure, the compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein X 3 is a phenyl group or a 6-membered heteroaryl group, wherein the phenyl group and the 6-membered heteroaryl group are each independently optionally substituted with one or more halogens, and preferably X 3 is selected from phenyl, pyridyl, pyrimidinyl, pyridazinyl and pyrazinyl, each of which is independently optionally substituted with one or more F, more preferably X 3 is a phenyl group, said phenyl group being optionally substituted with one or more F, most preferably X 3 is a phenyl group.

[0023] In some embodiments of the present disclosure, the compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein X 3 teeth [ka] and bonds marked with * are X 4 Of which, W 1 is N or CR 3d And W 2 is N or CR 3e And W 3 is N or CR 3f And W 4 is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, -(CH 2 ) n NRe R f , nitro group, hydroxy group, C 1-6 Hydroxyalkyl group, C 1-6 Aminoalkyl groups, C 1-6 Alkoxy C 1-6 Alkyl group, 3-8 membered cycloalkyl group 1-6 Alkyl group, 3-8 membered heterocyclyl C 1-6 R is selected from an alkyl group, a 3- to 8-membered cycloalkyl group, a 3- to 8-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; e and R f are the same or different and each independently represent a hydrogen atom or C 1-6 an alkyl group and n is 0, 1, 2 or 3; Preferably, W 1 is N or CR 3d And W 2 is N or CR 3e And W 3 is N or CR 3f And W 4 is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, More preferably, W 1 is N or CR 3d And W 2 is N or CR 3e And W 3 is N or CR 3f And W 4 is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6Alkyl group, C 1-6 Alkoxy groups and C 1-6 haloalkyl groups, More preferably, W 1 is N or CR 3d And W 2 is N or CR 3e And W 3 is N or CR 3f And W 4 is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom or a halogen (preferably F); Most preferably, W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom or a halogen (preferably F); Even more preferably, W 1 is CH and W 2 is CH and W 3 is CH and W 4 is CH.

[0024] In some embodiments of the present disclosure, the compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein X 3 teeth, [ka] The bonds marked with * are X. 4 is connected to R 3d , R 3e , R 3f , R 3g and R3h are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups and w is 0, 1, 2 or 3.

[0025] In some embodiments of the present disclosure, the compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein X 3 teeth, [ka] Selected from R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, preferably [ka] Selected from R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom or a halogen (preferably F), more preferably [ka] and more preferably selected from [ka] and most preferably [ka] and bonds marked with * are X 4 is linked to.

[0026] In some embodiments of the present disclosure, the present invention provides compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein J 2 is a 3- to 12-membered cycloalkyl group or a 3- to 12-membered heterocyclyl group, wherein the 3- to 12-membered cycloalkyl group and the 3- to 12-membered heterocyclyl group are each independently optionally selected from halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, -(CH 2 ) n NR g R h , nitro group, hydroxy group, C 1-6 Hydroxyalkyl group, C 1-6 Aminoalkyl groups, C 1-6 Alkoxy C 1-6 Alkyl group, 3-8 membered cycloalkyl group 1-6 Alkyl group, 3-8 membered heterocyclyl C 1-6 substituted with one or more substituents selected from an alkyl group, a 3- to 8-membered cycloalkyl group, a 3- to 8-membered heterocyclyl group, and ═O; R g and R h are the same or different and each independently represent a hydrogen atom or C 1-6 is an alkyl group, and n is 0, 1, 2, or 3.

[0027] In some embodiments of the present disclosure, the present invention provides compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein J 2 is a 3- to 12-membered cycloalkyl group or a 3- to 12-membered heterocyclyl group, and the 3- to 12-membered cycloalkyl group and the 3- to 12-membered heterocyclyl group are each independently optionally selected from halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6Haloalkyl group, C 1-6 substituted with one or more substituents selected from a haloalkoxy group, a cyano group, an amino group, a hydroxy group, and =O; Preferably, J 2 is a 3- to 12-membered heterocyclyl group, wherein the 3- to 12-membered heterocyclyl group is optionally selected from halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 substituted with one or more substituents selected from a haloalkoxy group, a cyano group, an amino group, a hydroxy group, and =O; More preferably, J 2 is a 3- to 8-membered monocyclic heterocyclyl group or a 7- to 11-membered spiroheterocyclyl group, and the 3- to 8-membered monocyclic heterocyclyl group and the 7- to 11-membered spiroheterocyclyl group are each independently optionally selected from halogen, C 1-6 Alkyl group and C 1-6 substituted with one or more substituents selected from haloalkyl groups; Even more preferably, J 2 is a 4- to 6-membered monocyclic heterocyclyl group or a 9- to 11-membered spiroheterocyclyl group, More preferably, J 2 is a piperidinyl group or a piperazinyl group.

[0028] In some embodiments of the present disclosure, the present invention provides compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein J 2 teeth, [ka] The bonds marked with * are selected from the following structures: 3 is connected to R 2c are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6is selected from a haloalkoxy group, a cyano group, an amino group, a hydroxy group, and =O, and is preferably a hydrogen atom; and k is 0, 1, 2, 3, 4, 5, or 6.

[0029] In some embodiments of the present disclosure, the present invention provides compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein J 2 teeth [ka] Among them, bonds marked with * are selected from J 3 is linked to.

[0030] In some embodiments of the present disclosure, the present invention provides compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein J 2 teeth [ka] Each R 2c are the same or different and each independently represent a halogen, C 1-6 Alkyl group, C 1-6 haloalkyl group and ═O, and k is 0, 1 or 2, preferably J 2 teeth [ka] More preferably, J 2 teeth [ka] and most preferably J 2 teeth [ka] Among them, the bonds marked with * are J 3 is linked to.

[0031] In some embodiments of the present disclosure, the compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentable salts thereof, wherein R 6a is a hydrogen atom or C 1-6 is an alkyl group, preferably R 6a is a hydrogen atom or a methyl group.

[0032] In some embodiments of the present disclosure, the compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentable salts thereof, wherein R 7a and R 8a are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, hydroxy group, amino group, cyano group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups and C 1-6 hydroxyalkyl groups, preferably R 7a and R 8a are the same or different and each independently represent a hydrogen atom, a halogen, a hydroxyl group, or C 1-6 More preferably, R 7a and R 8a are both hydrogen atoms.

[0033] In some embodiments of the present disclosure, the present invention provides compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein J 3 -O-, -S-, -NR 6a -, -C(O)-, -S(O) 2 -, -(CR 7a R 8a ) m3 -, C 2-6 Alkenyl group, C 2-6 alkynyl groups, 3- to 12-membered cycloalkyl groups, and 3- to 12-membered heterocyclyl groups, wherein the 3- to 12-membered cycloalkyl groups and the 3- to 12-membered heterocyclyl groups are each independently optionally selected from halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, -(CH 2 ) n NR g R h , nitro group, hydroxy group, C 1-6 Hydroxyalkyl group, C 1-6 Aminoalkyl groups, C 1-6 Alkoxy C 1-6 Alkyl group, 3-8 membered cycloalkyl group 1-6 Alkyl group, 3-8 membered heterocyclyl C 1-6 substituted with one or more substituents selected from an alkyl group, a 3- to 8-membered cycloalkyl group, a 3- to 8-membered heterocyclyl group, and ═O; R g and R h are the same or different and each independently represent a hydrogen atom or C 1-6 is an alkyl group, R 6a is a hydrogen atom or C 1-6 is an alkyl group, R 7a and R 8a are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, hydroxy group, amino group, cyano group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups and C 1-6 hydroxyalkyl groups; m3 is 0, 1, 2 or 3; and n is 0, 1, 2 or 3.

[0034] In some embodiments of the present disclosure, the present invention provides compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein J 3 -O-, -S-, -NR 6a -, -C(O)-, -S(O) 2 -, -(CR 7a R 8a ) m3 -, C 2-6 Alkenyl group, C 2-6 R is selected from an alkynyl group, a 3- to 8-membered cycloalkyl group, and a 3- to 8-membered heterocyclyl group; 6a is a hydrogen atom or C 1-6is an alkyl group, preferably a hydrogen atom or a methyl group; R 7a and R 8a are the same or different and each independently represent a hydrogen atom, a halogen, a hydroxyl group, or C 1-6 m3 is 0, 1, 2 or 3;

[0035] In some embodiments of the present disclosure, the present invention provides compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein J 3 CR 7a R 8a ) m3 - and R 7a and R 8a are the same or different and each independently represent a hydrogen atom, a halogen, a hydroxyl group, or C 1-6 m3 is selected from alkyl groups, preferably a hydrogen atom, and m3 is 0, 1, 2 or 3, preferably 0 or 1.

[0036] In some embodiments of the present disclosure, the present invention provides compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein J 3 Ha-(CH 2 ) m3 -, and m3 is 0, 1, 2 or 3, preferably 0 or 1.

[0037] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II) and formula (II-1) or a medicamentable salt thereof, wherein J 3 is a bond, -O-, -S-, -NH-, -N(CH 3 )-, -C(O)-, -S(O) 2 -, -CH 2 -, -CH(CH 3 )-, CH 2 CH 2 -, -CH 2 CH 2 CH 2 - and ethynylene groups, preferably J 3 is a bond or -CH2 -, more preferably J 3 Ha-CH 2 -It is.

[0038] In some embodiments of the present disclosure, the present invention provides compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein J 4 is selected from a bond, a 3- to 12-membered cycloalkyl group, a 3- to 12-membered heterocyclyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group, wherein the 3- to 12-membered cycloalkyl group, the 3- to 12-membered heterocyclyl group, the 6- to 10-membered aryl group, and the 5- to 10-membered heteroaryl group are each independently optionally selected from halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, -(CH 2 ) n NR g R h , nitro group, hydroxy group, C 1-6 Hydroxyalkyl group, C 1-6 Aminoalkyl groups, C 1-6 Alkoxy C 1-6 Alkyl group, 3-8 membered cycloalkyl group 1-6 Alkyl group, 3-8 membered heterocyclyl C 1-6 substituted with one or more substituents selected from an alkyl group, a 3- to 8-membered cycloalkyl group, a 3- to 8-membered heterocyclyl group, and ═O; R g and R h are the same or different and each independently represent a hydrogen atom or C 1-6 is an alkyl group, and n is 0, 1, 2, or 3.

[0039] In some embodiments of the present disclosure, the present invention provides compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein J 4 is a 3- to 12-membered cycloalkyl group or a 3- to 12-membered heterocyclyl group, and the 3- to 12-membered cycloalkyl group and the 3- to 12-membered heterocyclyl group are each independently optionally selected from halogen, C1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 substituted with one or more substituents selected from a haloalkoxy group, a cyano group, an amino group, a hydroxy group, and =O; Preferably, J 4 is a 3- to 8-membered cycloalkyl group or a 3- to 8-membered heterocyclyl group, and the 3- to 8-membered cycloalkyl group and the 3- to 8-membered heterocyclyl group are each independently optionally selected from halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 substituted with one or more substituents selected from a haloalkoxy group, a cyano group, an amino group, a hydroxy group, and =O; More preferably, J 4 is a 3- to 8-membered heterocyclyl group, which optionally includes halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 substituted with one or more substituents selected from a haloalkoxy group, a cyano group, an amino group, a hydroxy group, and =O; More preferably, J 4 is a 4- to 6-membered heterocyclyl group, which is optionally substituted with one or more =O; More preferably, J 4 is selected from a piperazinyl group, a piperidinyl group, and an azetidinyl group, each of which is independently optionally substituted with one or more =O groups; Most preferably, J 4 is selected from a piperazinyl group, a piperidinyl group, and an azetidinyl group.

[0040] In some embodiments of the present disclosure, the present invention provides compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein J 4is a bond or a 4- to 6-membered heterocyclyl group, which is optionally substituted with one or more =O, and preferably 4 is selected from a bond, a piperazinyl group, a piperidinyl group, and an azetidinyl group, each of which is independently optionally substituted with one or more =O, more preferably J 4 is a join, [ka] The bonds marked with * are selected from 5 is linked to.

[0041] In some embodiments of the present disclosure, the present invention provides compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein J 4 teeth, [ka] The bonds marked with * are selected from the structure 5 is connected to R 4a are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 is selected from a haloalkoxy group, a cyano group, an amino group, a hydroxy group, and =O, and is preferably a hydrogen atom; and z is 0, 1, 2, or 3.

[0042] In some embodiments of the present disclosure, the present invention provides compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein J 4 teeth, [ka] It was chosen because of the structure R 4a are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C1-6 Haloalkyl group, C 1-6 is selected from haloalkoxy, cyano, amino, hydroxy and =O, preferably a hydrogen atom, and z is 0, 1, 2 or 3, preferably J 4 teeth [ka] More preferably, J 4 teeth [ka] and bonds marked with * are J 5 is linked to.

[0043] In some embodiments of the present disclosure, the compound represented by the above general formula (I) and general formula (II) or a medicamentable salt thereof is a compound represented by general formula (G) or a medicamentable salt thereof: [ka] Among them, R 1a is a hydrogen atom, halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, Z 1 is N or CR 3b and Z 2 is N or CR 3c and R 3a , R 3b and R 3c are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, cyano group, amino group, nitro group, hydroxy group and C 1-6 hydroxyalkyl groups, Ring B and ring C are the same or different and each independently represent a 3- to 12-membered cycloalkyl group or a 3- to 12-membered heterocyclyl group, and the 3- to 12-membered cycloalkyl group and the 3- to 12-membered heterocyclyl group each independently optionally represent a halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 substituted with one or more substituents selected from a haloalkoxy group, a cyano group, an amino group, a hydroxy group, and =O; W 1 is N or CR 3d And W 2 is N or CR 3e And W 3 is N or CR 3f And W 4 is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, And m3, X 2 , J 1 , J 5 and A is as defined in general formula (I).

[0044] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II) and general formula (G) or a medicamentable salt thereof is a compound represented by general formula (G-1) or a medicamentable salt thereof: [ka] Among them, R 1a is a halogen, C 1-6 Alkyl group, C 1-6Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, and Ring B, Ring C, R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , m3, X 2 , J 1 , J 5 and A is as defined in general formula (G).

[0045] In some embodiments of the present disclosure, there is provided a compound represented by the above general formula (G) and general formula (G-1) or a medicamentable salt thereof, wherein ring B is a 3- to 12-membered heterocyclyl group, and the 3- to 12-membered heterocyclyl group optionally contains halogen, C 1-6 Alkyl group and C 1-6 haloalkyl groups, and preferably, ring B is a 3- to 8-membered monocyclic heterocyclyl group or a 7- to 11-membered spiroheterocyclyl group, and the 3- to 8-membered monocyclic heterocyclyl group and the 7- to 11-membered spiroheterocyclyl group are each independently optionally substituted with halogen, C 1-6 Alkyl group and C 1-6 More preferably, ring B is a 4- to 6-membered monocyclic heterocyclyl group or a 9- to 11-membered spiroheterocyclyl group, and even more preferably, ring B is [ka] More preferably, ring B is selected from [ka] and most preferably, ring B is [ka] Among them, the bonds marked with * are (CH 2) m3 is linked to.

[0046] In some embodiments of the present disclosure, the compounds represented by the above general formula (G) and general formula (G-1) or medicamentable salts thereof, wherein ring C is a 4- to 6-membered heterocyclyl group, the 4- to 6-membered heterocyclyl group is optionally substituted with one or more =O, preferably ring C is selected from a piperazinyl group, a piperidinyl group and an azetidinyl group, the piperazinyl group and the piperidinyl group are each independently optionally substituted with one or more =O, more preferably ring C is [ka] Most preferably, ring C is selected from [ka] and bonds marked with * are J 5 is linked to.

[0047] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), and general formula (G-1), or a medicamentable salt thereof, wherein R 7b and R 8b are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, hydroxy group, amino group, cyano group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups and C 1-6 hydroxyalkyl groups, preferably R 7b and R 8b are the same or different and each independently represent a hydrogen atom, a halogen, a hydroxyl group, or C 1-6 More preferably, R 7b and R 8b are both hydrogen atoms.

[0048] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), and general formula (G-1), or a medicamentable salt thereof, wherein R 6b is a hydrogen atom or C 1-6 is an alkyl group, preferably R 6b is a hydrogen atom or a methyl group.

[0049] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G) and general formula (G-1) or a medicamentable salt thereof, among which: 5 is -C(O)NR 6b -, -NR 6b C(O)-, -O-, -S-, -NR 6b -, -C(O)-, -S(O) 2 -, -(CR 7b R 8b ) m4 -, C 2-6 Alkenyl group, C 2-6 alkynyl groups, 3- to 12-membered cycloalkyl groups, and 3- to 12-membered heterocyclyl groups, wherein the 3- to 12-membered cycloalkyl groups and the 3- to 12-membered heterocyclyl groups are each independently optionally selected from halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, -(CH 2 ) n NR g R h , nitro group, hydroxy group, C 1-6 Hydroxyalkyl group, C 1-6 Aminoalkyl groups, C 1-6 Alkoxy C 1-6 Alkyl group, 3-8 membered cycloalkyl group 1-6 Alkyl group, 3-8 membered heterocyclyl C 1-6 substituted with one or more substituents selected from an alkyl group, a 3- to 8-membered cycloalkyl group, a 3- to 8-membered heterocyclyl group, and ═O; R g and R hare the same or different and each independently represent a hydrogen atom or C 1-6 is an alkyl group, n is 0, 1, 2 or 3, R 6b is a hydrogen atom or C 1-6 is an alkyl group, R 7b and R 8b are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, hydroxy group, amino group, cyano group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups and C 1-6 hydroxyalkyl groups; m4 is 0, 1, 2 or 3.

[0050] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G) and general formula (G-1) or a medicamentable salt thereof, among which: 5 is -C(O)NR 6b -, -NR 6b C(O)-, -O-, -S-, -NR 6b -, -C(O)-, -S(O) 2 -, -(CR 7b R 8b ) m4 -, C 2-6 Alkenyl group, C 2-6 R is selected from an alkynyl group, a 3- to 8-membered cycloalkyl group, and a 3- to 8-membered heterocyclyl group; 6b is a hydrogen atom or C 1-6 is an alkyl group, preferably a hydrogen atom or a methyl group; R 7b and R 8b are the same or different and each independently represent a hydrogen atom, a halogen, a hydroxyl group, or C 1-6 m4 is selected from alkyl groups, preferably a hydrogen atom; m4 is 0, 1, 2 or 3, preferably 0 or 1.

[0051] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G) and general formula (G-1) or a medicamentable salt thereof, among which:5 is a bond.

[0052] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G) and general formula (G-1) or a medicamentable salt thereof, among which: 5 -C(O)NR 6b -OR-NR 6b C(O)- and R 6b is a hydrogen atom or C 1-6 is an alkyl group, Preferably, J 5 -C(O)NR 6b -OR-NR 6b C(O)- and R 6b is a hydrogen atom or a methyl group, More preferably, J 5 is -C(O)NH-*, and the * end is linked to A.

[0053] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II) and general formula (G) or a medicamentable salt thereof is a compound represented by general formula (III′) or a medicamentable salt thereof: [ka] Among them, W 1 is N or CR 3d And W 2 is N or CR 3e And W 3 is N or CR 3f And W 4 is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, Z 3 , Z 4 , Z 5 and Z 6 are the same or different and each independently represent an N atom or CH; m3 is 0, 1, 2 or 3; x, x1, y, and y1 are each independently 0, 1, or 2; J 5 is -C(O)NR 6b -, -NR 6b C(O)-, -O-, -S-, -NR 6b -, -C(O)-, -S(O) 2 -, -(CR 7b R 8b ) m4 -, C 2-6 Alkenyl group, C 2-6 R is selected from an alkynyl group, a 3- to 8-membered cycloalkyl group, and a 3- to 8-membered heterocyclyl group; 6b is a hydrogen atom or C 1-6 is an alkyl group, R 7b and R 8b are the same or different and each independently represent a hydrogen atom, a halogen, a hydroxyl group, or C 1-6 m4 is 0, 1, 2 or 3, and preferably, 5 is selected from a bond, a 3- to 8-membered heterocyclyl group, and a 3- to 8-membered cycloalkyl group; Z 1 , Z 2 , R 1a , R 3a , X 2 , J 1 and A is as defined in general formula (G).

[0054] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (G) and general formula (III') or a medicamentable salt thereof is a compound represented by general formula (III'-1) or a medicamentable salt thereof: [ka] Among them, R 1a is a halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, and R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , x, x1, y, y1, m3, X 2 , J 1 , J 5 and A is as defined in general formula (III').

[0055] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III') and general formula (III'-1) or a medicamentable salt thereof, among which: 5 is selected from a bond, a 3- to 8-membered heterocyclyl group, and a 3- to 8-membered cycloalkyl group, preferably 5 is a bond or a piperazinyl group, more preferably J 5 is a bond.

[0056] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), and general formula (III'-1) or a medicamentable salt thereof, among which: 5 is selected from a bond, a 5- or 6-membered heterocyclyl group and -C(O)NH-, preferably 5 is selected from a bond, a piperazinyl group, and -C(O)NH-*, the * end being linked to A, and more preferably, J5 is a bond.

[0057] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (G) and general formula (III′) or a medicamentable salt thereof is a compound represented by general formula (III) or a medicamentable salt thereof: [ka] Among them, W 1 is N or CR 3d And W 2 is N or CR 3e And W 3 is N or CR 3f And W 4 is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, Z 3 , Z 4 , Z 5 and Z 6 are the same or different and each independently an N atom or CH, with the proviso that Z 3 and Z 4 At least one of the groups is a N atom, m3 is 0, 1, 2 or 3; x, x1, y, and y1 are each independently 0, 1, or 2; Z 1 , Z 2 , R 1a , R 3a , X 2 , J 1 and A is as defined in general formula (G).

[0058] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (G), general formula (III') and general formula (III) or a medicamentable salt thereof is a compound represented by general formula (III-1) or a medicamentable salt thereof: [ka] Among them, R 1a is a halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, and R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 3 , Z 4 , Z 5 , Z 6 , x, x1, y, y1, m3, X 2 , J 1 and A is as defined in general formula (III).

[0059] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III) and general formula (III-1) or a medicamentable salt thereof, wherein R 2a and R 2b are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, hydroxy group, amino group, cyano group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups and C 1-6 hydroxyalkyl groups, preferably R2a and R 2b are the same or different and each independently represent a hydrogen atom, a halogen, a hydroxyl group, or C 1-6 More preferably, R 2a and R 2b are both hydrogen atoms.

[0060] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III) and general formula (III-1) or a medicamentable salt thereof, wherein X 2 -C(O)-, -S(O) 2 -and-(CR 2a R 2b ) m1 - is selected from R 2a and R 2b are the same or different and each independently represent a hydrogen atom, a halogen, a hydroxyl group, or C 1-6 m1 is selected from alkyl groups, preferably a hydrogen atom, and m1 is 0, 1, 2 or 3.

[0061] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III) and general formula (III-1) or a medicamentable salt thereof, wherein X 2 is a bond or -C(O)-, preferably X 2 is a bond.

[0062] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III) and general formula (III-1) or a medicamentable salt thereof, wherein R 7 and R 8 are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C1-6 Alkoxy group, amino group, hydroxy group, cyano group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups and C 1-6 hydroxyalkyl groups, preferably R 7 and R 8 are the same or different and each independently represent a hydrogen atom, a halogen, a hydroxyl group, or C 1-6 More preferably, R 7 and R 8 are both hydrogen atoms.

[0063] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III) and general formula (III-1) or a medicamentable salt thereof, wherein R 6 is a hydrogen atom or C 1-6 is an alkyl group, preferably R 6 is a hydrogen atom or a methyl group.

[0064] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III) and general formula (III-1) or a medicamentable salt thereof, among which: 1 -O-, -S-, -NR 6 -, -C(O)-, -S(O) 2 -, -(CR 7 R 8 ) m2 -, C 2-6 Alkenyl groups and C 2-6 alkynyl groups, R 6 is a hydrogen atom or C 1-6 is an alkyl group, preferably a hydrogen atom or a methyl group; R 7 and R 8 are the same or different and each independently represent a hydrogen atom, a halogen, a hydroxyl group, or C 1-6m2 is 0, 1, 2 or 3; m3 is an alkyl group, preferably a hydrogen atom;

[0065] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III) and general formula (III-1) or a medicamentable salt thereof, among which: 1 is a bond, -O-, -S-, -NH-, -N(CH 3 )-, -C(O)-, -S(O) 2 -, -CH 2 -, -CH(CH 3 )-, -CH 2 CH 2 -, -CH 2 CH 2 CH 2 - and ethynylene groups, preferably J 1 is a bond, -O-, -S-, -CH 2 - and -C(O)-, more preferably J 1 is selected from a bond, -S- and -C(O)-, more preferably 1 is -S- or -C(O)-, and most preferably J 1 is -C(O)-.

[0066] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III) and general formula (III-1) or a medicamentable salt thereof, wherein X 2 is -C(O)- and J 1 is -S-.

[0067] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III) and general formula (III-1) or a medicamentable salt thereof, wherein X2 is a bond and J 1 is -C(O)-.

[0068] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II) and general formula (G) or a medicamentable salt thereof is a compound represented by general formula (X) or a medicamentable salt thereof: [ka] Among them, W 1 is N or CR 3d And W 2 is N or CR 3e And W 3 is N or CR 3f And W 4 is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, Z 4 , Z 5 and Z 6 are the same or different and each independently represent an N atom or CH; m3 is 0, 1, 2 or 3; h, i, u, and v are each independently 0 or 1; x1 and y1 are each independently 0, 1, or 2; Z 1 , Z 2 , R 1a , R 3a and A is as defined in general formula (II).

[0069] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (G) and general formula (X) or a medicamentable salt thereof is a compound represented by general formula (X-1) or a medicamentable salt thereof: [ka] Among them, R 1a is a halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, and R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , h, i, u, v, x1, y1, m3 and A are as defined in general formula (X).

[0070] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X) and general formula (X-1), or a medicamentable salt thereof, wherein Q 2 is a carbon atom and Q 1 , Q 3 , Q 4 and Q 5 are the same or different and each independently a nitrogen atom or CR′, R' may be the same or different and each independently represents a hydrogen atom, a halogen atom, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, C 1-6Hydroxyalkyl group, C 1-6 Aminoalkyl groups, C 1-6 Alkoxy C 1-6 Alkyl groups, cyano groups, hydroxy groups and -(CH 2 ) n NR c R d Selected from R c and R d are the same or different and each independently represent a hydrogen atom or C 1-6 an alkyl group and n is 0, 1, 2 or 3; Preferably, R' is the same or different and each independently represents a hydrogen atom, a halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, C 1-6 selected from a hydroxyalkyl group, a cyano group, a hydroxy group, and an amino group; More preferably, R' are the same or different and each independently represent a hydrogen atom, a halogen, a hydroxyl group, or C 1-6 selected from alkyl groups, More preferably, R' are the same or different and each independently represent a hydrogen atom or a halogen atom; Most preferably, R' are the same or different and each independently represent a hydrogen atom or a fluorine atom.

[0071] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X) and general formula (X-1) or a medicamentable salt thereof, among which: Q 2 is a carbon atom and Q 1 , Q 3 , Q 4 and Q 5 are the same or different and each independently a nitrogen atom or CR′; or Q 3 is a carbon atom and Q 1 , Q 2 , Q4 and Q 5 are the same or different and each independently a nitrogen atom or CR', R' may be the same or different and each independently represents a hydrogen atom, a halogen atom, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, C 1-6 Hydroxyalkyl group, C 1-6 Aminoalkyl groups, C 1-6 Alkoxy C 1-6 Alkyl groups, cyano groups, hydroxyl groups and (CH 2 ) n NR c R d Selected from R c and R d are the same or different and each independently represent a hydrogen atom or C 1-6 an alkyl group and n is 0, 1, 2 or 3; Preferably, R' is the same or different and each independently represents a hydrogen atom, a halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, C 1-6 selected from a hydroxyalkyl group, a cyano group, a hydroxy group, and an amino group; More preferably, R' are the same or different and each independently represent a hydrogen atom, a halogen, a hydroxyl group, or C 1-6 selected from alkyl groups, More preferably, R' are the same or different and each independently represent a hydrogen atom or a halogen atom; Most preferably, R' are the same or different and each independently represent a hydrogen atom or a fluorine atom.

[0072] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X) and general formula (X-1) or a medicamentable salt thereof, wherein R 1 is a hydrogen atom or C 1-6 is an alkyl group, preferably R 1 is a hydrogen atom.

[0073] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X) and general formula (X-1) or a medicamentable salt thereof, wherein R 2 is a hydrogen atom or C 1-6 is an alkyl group, preferably R 2 is a hydrogen atom.

[0074] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X) and general formula (X-1) or a medicamentable salt thereof, among which: [ka] is a single bond.

[0075] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X) and general formula (X-1), or a medicamentable salt thereof, wherein A is [ka] And Q1 , Q 2 , Q 3 , Q 4 and Q 5 is as defined in general formula (I), preferably Q 2 is a carbon atom and Q 1 , Q 3 , Q 4 and Q 5 are each independently CR', and R' is a hydrogen atom or a halogen atom, and more preferably, Q 2 is a carbon atom and Q 1 , Q 3 , Q 4 and Q 5 are each independently CR', and R' is a hydrogen atom or a fluorine atom, and most preferably, Q 2 is a carbon atom and Q 1 , Q 3 , Q 4 and Q 5 Both are CH.

[0076] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X) and general formula (X-1), or a medicamentable salt thereof, wherein A is [ka] It was chosen because of its structure. Q 1 , Q 2 , Q 3 , Q 4 and Q 5 are the same or different and each independently represent a nitrogen atom or CR', and R' are the same or different and each independently represent a hydrogen atom, a halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, C 1-6is selected from the group consisting of a hydroxyalkyl group, a cyano group, a hydroxy group and an amino group, and is preferably a hydrogen atom, a halogen atom, a hydroxy group and a C 1-6 It is an alkyl group, more preferably a hydrogen atom or a halogen, further preferably a hydrogen atom or a fluorine atom, and most preferably a hydrogen atom.

[0077] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X) and general formula (X-1), or a medicamentable salt thereof, wherein A is [ka] Selected from.

[0078] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X) and general formula (X-1), or a medicamentable salt thereof, wherein A is [ka] Selected from.

[0079] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X) and general formula (X-1), or a medicamentable salt thereof, wherein A is [ka] [ka] It is selected from the structure.

[0080] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X) and general formula (X-1), or a medicamentable salt thereof, wherein A is [ka] and preferably selected from the structures: [ka] It is.

[0081] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X) and general formula (X-1), or a medicamentable salt thereof, wherein A is [ka] and preferably [ka] and more preferably [ka] and most preferably [ka] and Among them, Q 1 , Q 3 , Q 2 , Q 4 and Q 5 is as defined in general formula (I), preferably Q 1 , Q 2 , Q 3 , Q4 and Q 5 are the same or different and each independently represent a nitrogen atom or CR', R' are the same or different and each independently represent a hydrogen atom or a halogen, and more preferably, Q 1 , Q 2 , Q 3 , Q 4 and Q 5 is CR', R' is the same or different and each independently represents a hydrogen atom or F, more preferably, Q 1 , Q 2 , Q 3 , Q 4 and Q 5 is CH.

[0082] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X) and general formula (X-1), or a medicamentable salt thereof, wherein A is [ka] and preferably [ka] More preferably, [ka] and most preferably [ka] It is.

[0083] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X) and general formula (X-1), or a medicamentable salt thereof, wherein A is [ka] and preferably [ka] More preferably, [ka] and most preferably [ka] It is.

[0084] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (G), general formula (III′) and general formula (III) or a medicamentable salt thereof is a compound represented by general formula (IV′) or a medicamentable salt thereof: [ka] Among them, Q 2 is a carbon atom and Q 1 , Q 3 , Q 4 and Q 5 are the same or different and each independently a nitrogen atom or CR′; or Q 3 is a carbon atom and Q 1 , Q 2 , Q 4 and Q 5 are the same or different and each independently a nitrogen atom or CR′, R' may be the same or different and each independently represents a hydrogen atom, a halogen atom, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, C 1-6 selected from the group consisting of hydroxyalkyl groups, cyano groups, hydroxy groups, and amino groups; Z 1 , Z2 , R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 4 , Z 5 , Z 6 , m3, x, x1, y and y1 are as defined in general formula (III').

[0085] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (G), general formula (III'), general formula (III) and general formula (IV') or a medicamentable salt thereof is a compound represented by general formula (IV'-1) or a medicamentable salt thereof: [ka] Among them, R 1a is a halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, preferably R 1a is C 1-6 More preferably, R 1a is a methyl group, Q 1 , Q 2 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV').

[0086] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (III'), general formula (III'-1), general formula (G), general formula (G-1), general formula (III), general formula (III-1), general formula (IV') and general formula (IV'-1) or a medicamentable salt thereof is a compound represented by general formula (IV'-1-1) or general formula (IV'-1-2) or a medicamentable salt thereof: [ka] or [ka] Among them, Q 1 , Q 2 , Q 3 , Q 4 , Q 5 , R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV'-1).

[0087] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (G), general formula (III′), general formula (III), general formula (IV′) or a medicamentable salt thereof is a compound represented by general formula (M) or a medicamentable salt thereof: [ka] Among them, Q 1 , Q 2 , Q 4 , Q 5 , R 1a , R 3a , W 1 , W 2 , W3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV').

[0088] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (IV'), general formula (IV'-1) and general formula (M) or a medicamentable salt thereof is a compound represented by general formula (M-1) or a medicamentable salt thereof: [ka] Among them, R 1a is a halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, preferably R 1a is C 1-6 More preferably, R 1a is a methyl group, Q 1 , Q 2 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (M).

[0089] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (IV'), general formula (IV'-1), general formula (M) and general formula (M-1) or a medicamentable salt thereof is a compound represented by general formula (M-1-1) or general formula (M-1-2) or a medicamentable salt thereof: [ka] [ka] Among them, Q 1 , Q 2 , Q 4 , Q 5 , R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (M-1).

[0090] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (G), general formula (III′) and general formula (III) or a medicamentable salt thereof is a compound represented by general formula (IV) or a medicamentable salt thereof: [ka] Among them, Q 1 , Q 3 , Q 4 and Q 5 are the same or different and each independently a nitrogen atom or CR′, R' may be the same or different and each independently represents a hydrogen atom, a halogen atom, C 1-6Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, C 1-6 selected from the group consisting of hydroxyalkyl groups, cyano groups, hydroxy groups, and amino groups; Z 1 , Z 2 , R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 4 , Z 5 , Z 6 , m3, x, x1, y and y1 are as defined in general formula (III).

[0091] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (G), general formula (III′), general formula (III) and general formula (IV) or a medicamentable salt thereof is a compound represented by general formula (IV-1) or a medicamentable salt thereof: [ka] Among them, R 1a is a halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, preferably R 1a is C 1-6 More preferably, R 1a is a methyl group, Q 1 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV).

[0092] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (IV) and general formula (IV-1) or a medicamentable salt thereof is a compound represented by general formula (IV-1-1) or general formula (IV-1-2) or a medicamentable salt thereof: [ka] [ka] Among them, Q 1 , Q 3 , Q 4 , Q 5 , R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV-1).

[0093] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (G), general formula (III′) and general formula (III) or a medicamentable salt thereof is a compound represented by general formula (V) or a medicamentable salt thereof: [ka] Among them, J 1 is a bond, O, S, -CH 2- and -C(O)-, Q 1 , Q 3 , Q 4 and Q 5 are the same or different and each independently a nitrogen atom or CR′, R' may be the same or different and each independently represents a hydrogen atom, a halogen atom, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, C 1-6 selected from the group consisting of hydroxyalkyl groups, cyano groups, hydroxy groups, and amino groups; Z 1 , Z 2 , R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 3 , Z 6 , m3, x, x1, y and y1 are as defined in general formula (III).

[0094] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (G), general formula (III′), general formula (III) and general formula (V) or a medicamentable salt thereof is a compound represented by general formula (V-1) or a medicamentable salt thereof: [ka] Among them, R 1a is a halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, preferably R 1a is C 1-6 More preferably, R 1a is a methyl group, J1 , Q 1 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 3 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (V).

[0095] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (V) and general formula (V-1) or a medicamentable salt thereof is a compound represented by general formula (V-1-1) or general formula (V-1-2) or a medicamentable salt thereof: [ka] or [ka] Among them, J 1 , Q 1 , Q 3 , Q 4 , Q 5 , R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 3 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (V-1).

[0096] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2) or a medicamentous salt thereof, wherein Z 1 is CR 3b and Z 2 is CR 3c and R 3a , R 3b and R 3c are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, cyano group, amino group, nitro group, hydroxy group and C 1-6 hydroxyalkyl groups, Preferably, Z 1 is CR 3b and Z 2 is CR 3c and R 3a , R 3b and R 3c are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, cyano group and C 1-6 haloalkyl groups, more preferably Z 1 is CR 3b and Z 2 is CR 3c and R 3b and R 3c are both hydrogen atoms, and R 3a is a hydrogen atom, halogen, C 1-6 Alkyl group, C 1-6Alkoxy group, cyano group and C 1-6 haloalkyl groups, More preferably, Z 1 is CR 3b and Z 2 is CR 3c and R 3b and R 3c are both hydrogen atoms, and R 3a is a halogen, Most preferably, Z 1 is CR 3b and Z 2 is CR 3c and R 3b and R 3c are both hydrogen atoms, and R 3a is a chlorine atom.

[0097] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2) or a medicamentous salt thereof, wherein Z 1 is CR 3b and Z 2 is CR 3c and R 3a is halogen or C 1-6 is a haloalkyl group, R 3b is a hydrogen atom, and R 3c is a hydrogen atom or C 1-6 is an alkyl group, preferably Z 1 is CR 3b and Z 2 is CR 3c and R 3a is Cl or a trifluoromethyl group, and R 3bis a hydrogen atom, and R 3c is a hydrogen atom or a methyl group.

[0098] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2), or a medicamentable salt thereof, among which: [ka] teeth, [ka] and preferably selected from the structures: [ka] teeth [ka] More preferably, [ka] teeth [ka] It is.

[0099] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2) or a medicamentous salt thereof, wherein W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, Preferably, W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group and C 1-6 It is selected from haloalkyl groups.

[0100] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2) or a medicamentous salt thereof, wherein W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, Preferably, W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group and C 1-6 haloalkyl groups, More preferably, W 1 is CR 3d And W2 is CR 3e And W 3 is CR 3f And W 4 is CR 3g and R 3d , R 3e , R 3f and R 3g are both hydrogen atoms.

[0101] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2) or a medicamentous salt thereof, wherein W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is N and R 3d , R 3e and R 3f are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy groups, cyano groups, amino groups, hydroxy groups and C 1-6 hydroxyalkyl groups, Preferably, W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is N and R 3d , R 3e and R3f are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group and C 1-6 haloalkyl groups, More preferably, W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is N and R 3d , R 3e and R 3f are both hydrogen atoms.

[0102] In some embodiments of the present disclosure, the present invention is directed to a compound represented by the above general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2) or a medicamentable salt thereof, among which: W 1 is N or CR 3d And W 2 is N or CR 3e And W 3 is N or CR 3f And W 4 is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group and C 1-6 haloalkyl groups, preferably W 1 is CR 3d And W 2 is CR 3e And W 3 is CR3f And W 4 is CR 3g or W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is N, or W 1 is N and W 2 is CR 3e And W 3 is CR 3f And W 4 is N, or W 1 is CR 3d And W 2 is N and W 3 is CR 3f And W 4 is N, or W 1 is CR 3d And W 2 is N and W 3 is CR 3f And W 4 is CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group and C 1-6 It is selected from haloalkyl groups, and is preferably a hydrogen atom or a halogen, more preferably a hydrogen atom or a fluorine atom, and most preferably a hydrogen atom.

[0103] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2) or a medicamentous salt thereof, wherein W 1 is N or CR 3d And W 2 is N or CR 3e And W 3 is N or CR 3f And W 4 is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom or a halogen (preferably F); Preferably, W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom or a halogen atom, More preferably, W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is CR 3g and R 3d , R 3e , R 3f and R3g are the same or different and each independently represent a hydrogen atom or a fluorine atom, More preferably, W 1 is CF or CH, W 2 is CH and W 3 is CH and W 4 is CH, Most preferably, W 1 is CF and W 2 is CH and W 3 is CH and W 4 is CH.

[0104] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2) or a medicamentable salt thereof, wherein R 1a is C 1-6 It is an alkyl group, preferably a methyl group.

[0105] In some embodiments of the present disclosure, the compounds represented by the above general formula (II), general formula (G), general formula (III′), general formula (III), general formula (X), general formula (IV′), general formula (M), general formula (IV), and general formula (V) or medicamentable salts thereof, wherein R 1a is a hydrogen atom or C 1-6 It is an alkyl group, and is preferably a hydrogen atom or a methyl group.

[0106] In some embodiments of the present disclosure, the compounds represented by the above general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2) or medicamentous salts thereof are1 is -S-.

[0107] In some embodiments of the present disclosure, the present invention relates to a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), or a medicamentable salt thereof, wherein Q 2 is a carbon atom and Q 1 , Q 3 , Q 4 and Q 5 are the same or different and each independently a nitrogen atom or CR′; or Q 3 is a carbon atom and Q 1 , Q 2 , Q 4 and Q 5 are the same or different and each independently a nitrogen atom or CR′; or Q 4 is a carbon atom and Q 1 , Q 2 , Q 3 and Q 5 are the same or different and each independently represent a nitrogen atom or CR', and R' represents a hydrogen atom, a halogen atom, or C 1-6 selected from alkyl groups, Preferably, Q 2 is a carbon atom and Q 1 , Q 3 , Q 4 and Q 5 are the same or different and each independently a nitrogen atom or CR′; or Q 3 is a carbon atom and Q 1 , Q 2 , Q 4 and Q 5 are the same or different and each independently represent a nitrogen atom or CR', and R' represents a hydrogen atom, a halogen atom, or C 1-6 selected from alkyl groups, More preferably, Q 3 is a carbon atom and Q 1 , Q2 , Q 4 and Q 5 are the same or different and each independently a nitrogen atom or CR′; or Q 2 is a carbon atom and Q 1 , Q 3 , Q 4 and Q 5 are the same or different and each independently represent a nitrogen atom or CR', and R' represents a hydrogen atom or a halogen atom; More preferably, Q 3 is a carbon atom and Q 1 , Q 2 , Q 4 and Q 5 are the same or different and each independently represent a nitrogen atom or CR', and R' represents a hydrogen atom or a halogen atom; More preferably, Q 3 is a carbon atom and Q 1 , Q 2 , Q 4 and Q 5 are each independently CR', and R' is a hydrogen atom or a halogen atom; More preferably, Q 3 is a carbon atom and Q 1 , Q 2 , Q 4 and Q 5 are each independently CR', and R' is a hydrogen atom or a fluorine atom. More preferably, Q 3 is a carbon atom and Q 1 , Q 4 and Q 5 is CH and Q 2 is a hydrogen atom or F, Most preferably, Q 3 is a carbon atom and Q 1 , Q 2 , Q 4 and Q 5 Both are CH.

[0108] In some embodiments of the present disclosure, the compounds represented by the above general formula (M), general formula (M-1), general formula (M-1-1) and general formula (M-1-2) or medicamentous salts thereof, among which Q 1 , Q 2 , Q 4 and Q 5 are each independently a nitrogen atom or CR', and R' is a hydrogen atom or a halogen atom; Preferably, Q 1 , Q 2 , Q 4 and Q 5 are each independently CR', and R' is a hydrogen atom or a halogen atom; More preferably, Q 1 , Q 2 , Q 4 and Q 5 are each independently CR', and R' is a hydrogen atom or a fluorine atom; Most preferably, Q 1 , Q 2 , Q 4 and Q 5 Both are CH.

[0109] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2) or a medicamentable salt thereof, wherein Q 1 , Q 3 , Q 4 and Q 5 are each independently a nitrogen atom or CR', and R' is a hydrogen atom, a halogen atom, or C 1-6 selected from alkyl groups, Preferably, Q 1 , Q 3 , Q 4 and Q 5 are each independently CR', and R' is a hydrogen atom or a halogen atom; More preferably, Q 1 , Q 3 , Q 4 and Q 5are each independently CR', and R' is a hydrogen atom or a fluorine atom; Most preferably, Q 1 , Q 3 , Q 4 and Q 5 Both are CH.

[0110] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2) or a medicamentable salt thereof, wherein Q 1 , Q 3 and Q 5 is CR 0 And Q 4 is N or CR 01 and R 0 and R 01 are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 Haloalkoxy group, C 1-6 selected from a hydroxyalkyl group, a cyano group, a hydroxy group, and an amino group; Preferably, Q 1 , Q 3 and Q 5 is CR 0 And Q 4 is N or CR 01 and R 0 is a hydrogen atom, and R 01 is a hydrogen atom or a halogen (preferably F), More preferably, Q 1 , Q 3 and Q 5 is CR 0 And Q 4 is CR 01 and R 0 is a hydrogen atom, and R 01 is a hydrogen atom or a halogen (preferably F).

[0111] In some embodiments of the present disclosure, the general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), compounds represented by general formula (M-1), general formula (M-1-1) and general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2), or medicinal salts thereof, wherein m3 is 0 or 1, and preferably m3 is 1.

[0112] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1) and general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1) and general formula (IV-1-2), or a medicamentable salt thereof, wherein Z 4 is CH and Z 5 is N and Z 6 is N or CH.

[0113] In some embodiments of the present disclosure, the compounds represented by the above general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2) or medicamentous salts thereof, among which Z 6 is a N atom.

[0114] In some embodiments of the present disclosure, the compounds represented by the above general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2) or medicamentous salts thereof, among which Z 3 is CH.

[0115] In some embodiments of the present disclosure, the compounds represented by the above general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2) or medicamentous salts thereof, among which Z 3 is CH and Z 6 is N.

[0116] In some embodiments of the present disclosure, the compound represented by the above general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1) and general formula (V-1-2) or a medicamentable salt thereof, wherein x, x1, y, and y1 are each independently 0 or 1, and preferably, x, x1, y, and y1 are 1.

[0117] In some embodiments of the present disclosure, the compound represented by the above general formula (X) and general formula (X-1) or a medicament salt thereof, wherein x1 and y1 are each independently 0 or 1, and preferably, x1 and y1 are 1.

[0118] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (G), general formula (III′), general formula (III) and general formula (IV) or a medicamentable salt thereof is a compound represented by general formula (VI) or a medicamentable salt thereof: [ka] Among them, R 1a is C 1-6 is an alkyl group, Q 4 is a nitrogen atom or CR 01 and R 01 is a hydrogen atom or a halogen, W4 is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group and C 1-6 haloalkyl groups, Z 4 is N or CH, Z 5 is N or CH, m3 is 0 or 1; x, x1, y, and y1 each independently represent 0 or 1.

[0119] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (G), general formula (III′), general formula (III), general formula (IV) and general formula (VI) or a medicamentable salt thereof is a compound represented by general formula (VI-1) or a medicamentable salt thereof: [ka] Among them, R 1a , Q 4 , R 3d , R 3e , R 3f , W 4 , Z 4 , Z 5 , m3, x, x1, y and y1 are as defined in general formula (VI).

[0120] In some embodiments of the present disclosure, the compounds represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (IV), general formula (IV-1), general formula (VI) and general formula (VI-1) or medicinal salts thereof are represented by general formula (VI-1-1) and general formula (VI-1-2) or medicinal salts thereof: [ka] or [ka] Among them, R 1a , Q 4 , R 3d , R 3e , R 3f , W 4 , Z 4 , Z 5 , m3, x, x1, y and y1 are as defined in general formula (VI-1).

[0121] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (G), general formula (III′), general formula (III) and general formula (V) or a medicamentable salt thereof is a compound represented by general formula (VII) or a medicamentable salt thereof: [ka] Among them, R 1a is C 1-6 is an alkyl group, Q 4 is a nitrogen atom or CR 01 and R 01 is a hydrogen atom or a halogen, W 4 is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group and C 1-6 haloalkyl groups, m3 is 0 or 1; x, x1, y, and y1 each independently represent 0 or 1.

[0122] In some embodiments of the present disclosure, the compound represented by the above general formula (I), general formula (II), general formula (G), general formula (III′), general formula (III), general formula (V) and general formula (VII) or a medicamentable salt thereof is a compound represented by general formula (VII-1) or a medicamentable salt thereof: [ka] Among them, R 1a , Q 4 , R 3d , R 3e , R 3f , W 4 , m3, x, x1, y and y1 are as defined in general formula (VII).

[0123] In some embodiments of the present disclosure, the compounds represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (V), general formula (V-1), general formula (VII) and general formula (VII-1) or medicinal salts thereof are represented by general formula (VII-1-1) and general formula (VII-1-2) or medicinal salts thereof: [ka] [ka] Among them, R 1a , Q 4 , R 3d , R 3e , R 3f , W 4 , m3, x, x1, y and y1 are as defined in general formula (VII-1).

[0124] In some embodiments of the present disclosure, the compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein X 4 Ha-J1 -J 2 -J 3 -J 4 -J 5 -Of which, J 1 isX 3 Connected to J 1 is a bond, O, S, -CH 2 - and -C(O)-, J 2 is a 3- to 12-membered heterocyclyl group, the 3- to 12-membered heterocyclyl group optionally containing halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 substituted with one or more substituents selected from a haloalkoxy group, a cyano group, an amino group, a hydroxy group, and =O; 3 Ha-(CH 2 ) m3 -, m3 is 0 or 1, J 4 is a 3- to 8-membered heterocyclyl group, which optionally includes halogen, C 1-6 Alkyl group, C 1-6 Alkoxy group, C 1-6 Haloalkyl group, C 1-6 substituted with one or more substituents selected from a haloalkoxy group, a cyano group, an amino group, a hydroxy group, and =O; 5 is selected from a bond, a 3- to 8-membered heterocyclyl group, and a 3- to 8-membered cycloalkyl group.

[0125] In some embodiments of the present disclosure, the compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein X 4 Ha-J 1 -J 2 -J 3 -J 4 -J 5 -Of which, J 1 isX 3 Connected to J 1 is -S- or -C(O)-, J 2 is a 4- to 6-membered monocyclic heterocyclyl group or a 9- to 11-membered spiroheterocyclyl group; 3is a bond or -CH 2 - and J 4 is a bond or a 4- to 6-membered heterocyclyl group, the 4- to 6-membered heterocyclyl group being optionally substituted with one or more =O; J 5 is selected from a bond, a 5- or 6-membered heterocyclyl group, and -C(O)NH-*, the * terminus being linked to A; Preferably, X 4 Ha-J 1 -J 2 -J 3 -J 4 -J 5 -Of which, J 1 isX 3 Connected to J 1 is -S- or -C(O)-, J 2 teeth, [ka] Among them, bonds marked with * are selected from J 3 Connected to J 3 is a bond or -CH 2 - and J 4 is a join, [ka] The bonds marked with * are selected from 5 Connected to J 5 is selected from a bond, a piperazinyl group, and -C(O)NH-*, the * end being linked to A; More preferably, X 4 Ha-J 1 -J 2 -J 3 -J 4 -J 5 -Of which, J 1 isX 3 Connected to J 1 is -C(O)-, and J 2 teeth [ka] Among them, the bonds marked with * are J 3 Connected to J 3Ha-CH 2 - and J 4 teeth [ka] and bonds marked with * are J 5 Connected to J 5 is a bond.

[0126] In some embodiments of the present disclosure, the compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein X 4 , i.e., -J 1 -J 2 -J 3 -J 4 -J 5 -teeth, [ka] The bond marked with * is connected to A.

[0127] In some embodiments of the present disclosure, the compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein X 4 , i.e., -J 1 -J 2 -J 3 -J 4 -J 5 -teeth, [ka] The bond marked with * is connected to A.

[0128] In some embodiments of the present disclosure, the compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein X 4 , i.e., -J 1 -J 2 -J 3 -J 4 -J 5 -teeth, [ka] and preferably [ka] and more preferably [ka] and the bond marked with an * is connected to A.

[0129] In some embodiments of the present disclosure, the compounds represented by the above general formula (I), general formula (II) and general formula (II-1) or medicamentous salts thereof, wherein X 4 , i.e., -J 1 -J 2 -J 3 -J 4 -J 5 -teeth, [ka] The bond marked with * is connected to A.

[0130] In some embodiments of the present disclosure, there is provided a compound represented by the above general formula (G) or a medicamentable salt thereof, wherein Z 1 is CR 3b and Z 2 is CR 3c and R 3a is halogen or C 1-6 is a haloalkyl group, R 3b is a hydrogen atom, and R 3c is a hydrogen atom or C 1-6 is an alkyl group, R 1a is a hydrogen atom or C 1-6 is an alkyl group, and X 2 is a bond or -C(O)-, W 1 is N or CR 3d And W 2 is N or CR 3e And W 3 is N or CR 3f And W 4 is N or CR3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom or a halogen atom; J 1 is -S- or -C(O)-; ring B is a 4- to 6-membered monocyclic heterocyclyl group or a 9- to 11-membered spiroheterocyclyl group; m3 is 0 or 1; ring C is a 4- to 6-membered heterocyclyl group, which is optionally substituted with one or more =O; J 5 is selected from a bond, a 5- or 6-membered heterocyclyl group, and -C(O)NH-*, the * terminus being linked to A, and A is [ka] It was chosen because of the structure, Q 1 , Q 2 , Q 3 , Q 4 and Q 5 are the same or different and each independently represent a nitrogen atom or CR', and R' are the same or different and each independently represent a hydrogen atom or a halogen.

[0131] In some embodiments of the present disclosure, there is provided a compound represented by the above general formula (G-1) or a medicamentable salt thereof, wherein Z 1 is CR 3b and Z 2 is CR 3c and R 3a is halogen or C 1-6 is a haloalkyl group, R 3b is a hydrogen atom, and R 3c is a hydrogen atom or C 1-6 is an alkyl group, R 1a is C 1-6 is an alkyl group, and X 2 is a bond or -C(O)-, W 1 is N or CR 3d And W 2 is N or CR 3e And W 3 is N or CR 3f And W 4is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom or a halogen atom; J 1 is -S- or -C(O)-; ring B is a 4- to 6-membered monocyclic heterocyclyl group or a 9- to 11-membered spiroheterocyclyl group; m3 is 0 or 1; ring C is a 4- to 6-membered heterocyclyl group, which is optionally substituted with one or more =O; J 5 is selected from a bond, a 5- or 6-membered heterocyclyl group, and -C(O)NH-*, the * terminus being linked to A, and A is [ka] It was chosen because of the structure, Q 1 , Q 2 , Q 3 , Q 4 and Q 5 are the same or different and each independently represent a nitrogen atom or CR', and R' are the same or different and each independently represent a hydrogen atom or a halogen.

[0132] In some embodiments of the present disclosure, the compounds represented by the above general formula (M), general formula (M-1), general formula (M-1-1) and general formula (M-1-2) or medicamentous salts thereof are [ka] teeth [ka] Selected from R 1a is C 1-6 is an alkyl group, W 1 is N or CR 3d And W 2 is N or CR 3e And W 3 is N or CR 3f And W 4 is N or CR 3g and R3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom or a halogen; m3 is 0 or 1; x, x1, y, and y1 are each independently 0 or 1; Z 4 , Z 5 , Z 6 are each independently CH or N, and Q 1 , Q 2 , Q 4 and Q 5 are each independently a nitrogen atom or CR', and R' is a hydrogen atom or a halogen.

[0133] In some embodiments of the present disclosure, the compounds represented by the above general formula (IV'), general formula (IV'-1), general formula (IV'-1-1) and general formula (IV'-1-2) or medicamentable salts thereof, among which Z 1 is CR 3b and Z 2 is CR 3c and R 3b and R 3c are both hydrogen atoms, and R 3a is a halogen, and R 1a is C 1-6 is an alkyl group, W 1 is N or CR 3d And W 2 is N or CR 3e And W 3 is N or CR 3f And W 4 is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom, a halogen, or C 1-6 Alkyl group and C 1-6 haloalkyl groups; Z 4 is CH and Z 5 is N and Z 6 is N or CH; x, x1, y, and y1 are each independently 0 or 1; m3 is 0 or 1; Q 2is a carbon atom and Q 1 , Q 3 , Q 4 and Q 5 are the same or different and each independently a nitrogen atom or CR′; or Q 3 is a carbon atom and Q 1 , Q 2 , Q 4 and Q 5 are the same or different and each independently represent a nitrogen atom or CR', and R' represents a hydrogen atom, a halogen atom, or C 1-6 It is selected from alkyl groups.

[0134] In some embodiments of the present disclosure, the compound represented by the above general formula (IV'), general formula (IV'-1), general formula (IV'-1-1) and general formula (IV'-1-2) or a medicamentable salt thereof, among which: [ka] teeth [ka] and R 1a is a methyl group, and W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is CR 3g or W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is N, or W 1 is N and W 2 is CR 3e And W 3 is CR 3f And W 4 is N, or W 1 is CR 3d And W 2 is N and W 3is CR 3f And W 4 is N, or W 1 is CR 3d And W 2 is N and W 3 is CR 3f And W 4 is CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom or a halogen atom; Z 4 is CH and Z 5 is N and Z 6 is N or CH; x, x1, y, and y1 are each independently 0 or 1; m3 is 0 or 1; Q 3 is a carbon atom and Q 1 , Q 2 , Q 4 and Q 5 are the same or different and each independently a nitrogen atom or CR', and R' is a hydrogen atom or a halogen.

[0135] In some embodiments of the present disclosure, the compound represented by the above general formula (IV'), general formula (IV'-1), general formula (IV'-1-1) and general formula (IV'-1-2) or a medicamentable salt thereof, among which: [ka] teeth [ka] and R 1a is a methyl group, and W 1 is CF or CH, W 2 is CH and W 3 is CH and W 4 is CH and Z 4 is CH and Z 5 is N and Z 6 is N or CH; x, x1, y, and y1 are each independently 0 or 1; m3 is 0 or 1; Q 3is a carbon atom and Q 1 , Q 2 , Q 4 and Q 5 are each independently CR', and R' is a hydrogen atom or a halogen.

[0136] In some embodiments of the present disclosure, the compound represented by the above general formula (X) and general formula (X-1) or a medicamentable salt thereof, wherein: [ka] teeth [ka] and R 1a is a methyl group, and W 1 is N or CR 3d And W 2 is N or CR 3e And W 3 is N or CR 3f And W 4 is N or CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently selected from a hydrogen atom or a halogen; Z 4 is CH and Z 5 is N and Z 6 is N or CH; h, i, u, v, x1 and y1 are each independently 0 or 1; m3 is 0 or 1; A is [ka] And Q 2 is a carbon atom and Q 1 , Q 3 , Q 4 and Q 5 are the same or different and each independently a nitrogen atom or CR', where R' is a hydrogen atom or a halogen.

[0137] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (IV), general formula (IV-1), general formula (IV-1-1) and general formula (IV-1-2) or a medicamentable salt thereof, among which: [ka] teeth [ka] and R 1a is a methyl group, and W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is CR 3g or W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is N, or W 1 is N and W 2 is CR 3e And W 3 is CR 3f And W 4 is N, or W 1 is CR 3d And W 2 is N and W 3 is CR 3f And W 4 is N, or W 1 is CR 3d And W 2 is N and W 3 is CR 3f And W 4 is CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom or a halogen atom; Z 4 is CH and Z 5 is N and Z6 is N or CH; x, x1, y, and y1 are each independently 0 or 1; m3 is 0 or 1; Q 1 , Q 3 , Q 4 and Q 5 are each independently CR', and R' is a hydrogen atom or a halogen.

[0138] In some embodiments of the present disclosure, the present invention provides a compound represented by the above general formula (V), general formula (V-1), general formula (V-1-1), and general formula (V-1-2) or a medicamentable salt thereof, among which: [ka] teeth [ka] and R 1a is a methyl group, and W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is CR 3g or W 1 is CR 3d And W 2 is CR 3e And W 3 is CR 3f And W 4 is N, or W 1 is N and W 2 is CR 3e And W 3 is CR 3f And W 4 is N, or W 1 is CR 3d And W 2 is N and W 3 is CR 3f And W 4 is N, or W 1 is CR 3d And W 2 is N and W 3 is CR3f And W 4 is CR 3g and R 3d , R 3e , R 3f and R 3g are the same or different and each independently represent a hydrogen atom or a halogen atom; J 1 is -S- and Z 3 is CH and Z 6 is N, x, x1, y, and y1 are each independently 0 or 1, m3 is 0 or 1, and Q 1 , Q 3 , Q 4 and Q 5 are each independently CR', and R' is a hydrogen atom or a halogen.

[0139] [Table 1-1]

[0140] [Table 1-2]

[0141] [Table 1-3]

[0142] [Table 1-4]

[0143] [Table 1-5]

[0144] [Table 1-6]

[0145] [Table 1-7]

[0146]

Table 1-8

[0147]

Table 1-9

[0148]

Table 1-10

[0149]

Table 1-11

[0150]

Table 1-12

[0151]

Table 1-13

[0152]

Table 1-14

[0153]

Table 1-15

[0154]

Table 1-16

[0155]

Table 1-17

[0156]

Table 1-18

[0157]

Table 1-19

[0158]

Table 1-20

[0159]

Table 1-21

[0160]

Table 1-22

[0161]

Table 1-23

[0162]

Table 1-24

[0163]

Table 1-25

[0164]

Table 1-26

[0165]

Table 1-27

[0166]

Table 1-28

[0167]

Table 1-29

[0168]

Table 1-30

[0169]

Table 1-31

[0170]

Table 1-32

[0171]

Table 1-33

[0172]

Table 1-34

[0173]

Table 1-35

[0174]

Table 1-36

[0175]

Table 1-37

[0176]

Table 1-38

[0177]

Table 1-39

[0178]

Table 1-40

[0179]

Table 1-41

[0180]

Table 1-42

[0181]

Table 1-43

[0182]

Table 1-44

[0183]

Table 1-45

[0184]

Table 1-46

[0185]

Table 1-47

[0186]

Table 1-48

[0187]

Table 1-49

[0188]

Table 1-50

[0189]

Table 1-51

[0190]

Table 1-52

[0191]

Table 1-53

[0192]

Table 1-54

[0193]

Table 1-55

[0194]

Table 1-56

[0195]

Table 1-57

[0196]

Table 1-58

[0197] [Table 1-59]

[0198] [Table 1-60]

[0199] [Table 1-61]

[0200] [Table 1-62]

[0201] [Table 1-63]

[0202] [Table 1-64]

[0203] The present disclosure further provides a compound represented by the general formula (XB) or a salt thereof: [ka] Among them, Z 4 , Z 5 , Z 6 , h, i, u, v, x1, y1, m3 and A are as defined in general formula (X).

[0204] The present disclosure further provides a compound represented by the general formula (MB) or a salt thereof: [ka] Among them, Q 1 , Q 2 , Q 4 , Q 5 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (M).

[0205] The present disclosure further provides a compound represented by the general formula (VA) or a salt thereof: [ka] Among them, J 1 , R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 3 , x and y are as defined in general formula (V).

[0206] The present disclosure further provides a compound represented by general formula (V-1A) or a salt thereof: [ka] Among them, J 1 , R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 3 , x and y are as defined in general formula (V-1).

[0207] The present disclosure further provides a compound represented by general formula (VIIA) or a salt thereof: [ka] Among them, R 1a , R 3d , R 3e , R 3f , W 4 , x and y are as defined in general formula (VII).

[0208] The present disclosure further provides a compound represented by general formula (VII-1A) or a salt thereof: [ka] Among them, R 1a , R 3d , R 3e , R 3f , W 4 , x and y are as defined in general formula (VII-1).

[0209] The present disclosure further provides a compound represented by general formula (VB) or a salt thereof: [ka] Among them, Q 1 , Q 3 , Q 4 , Q 5 , Z 6 , x1 and y1 are as defined in general formula (V).

[0210] The present disclosure further provides a compound represented by general formula (VIIB) or a salt thereof: [ka] Among them, Q 4 , x1 and y1 are as defined in general formula (VII).

[0211] [Table 2-1]

[0212] [Table 2-2]

[0213]

Table 2-3

[0214]

Table 2-4

[0215]

Table 2-5

[0216]

Table 2-6

[0217]

Table 2-7

[0218]

Table 2-8

[0219]

Table 2-9

[0220]

Table 2-10

[0221]

Table 2-11

[0222]

Table 2-12

[0223] [Table 2-13]

[0224] [Table 2-14]

[0225] [Table 2-15]

[0226] [Table 2-16]

[0227] Another aspect of the present disclosure relates to a method for preparing a compound of general formula (III') or a medicamentable salt thereof, comprising: [ka] A method for producing a compound represented by general formula (III'A) or a salt thereof and a compound represented by general formula (III'B) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) by a condensation reaction, the compound represented by general formula (III') or a medicamentous salt thereof is obtained, Among them, J 1 is -C(O)-, Z 3 is N, A, R 1a , R 3a , J 5 , X 2 , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (III').

[0228] Another aspect of the present disclosure relates to a method for preparing a compound of general formula (III') or a medicamentable salt thereof, comprising: [ka] The method includes subjecting a compound represented by general formula (III'C) or a salt thereof to a reductive amination reaction with a compound represented by general formula (III'E) or a salt thereof (preferably hydrochloride and trifluoroacetate) to obtain a compound represented by general formula (III') or a medicamentable salt thereof, wherein m3 is 1, 2 or 3; Alternatively, a compound represented by general formula (III'D) or a salt thereof and a compound represented by general formula (III'E) or a salt thereof (preferably hydrochloride and trifluoroacetate) are subjected to a reductive amination reaction to obtain a compound represented by general formula (III') or a medicamentable salt thereof, in which m3 is 0; Among them, m6 is 0, 1 or 2; Z 4 is CH, Z 5 is N, A, J 1 , J 5 , X 2 , R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 3 , Z 6 , x, x1, y and y1 are as defined in general formula (III').

[0229] Another aspect of the present disclosure relates to a method for preparing a compound of general formula (III') or a medicamentable salt thereof, comprising: [ka] The method includes subjecting a compound represented by general formula (III'F) or a salt thereof (preferably hydrochloride and trifluoroacetate) to a reductive amination reaction with a compound represented by general formula (III'G) or a salt thereof to obtain a compound represented by general formula (III') or a medicamentable salt thereof, wherein m3 is 0; Alternatively, a compound represented by general formula (III'F) or a salt thereof (preferably hydrochloride and trifluoroacetate) is subjected to a reductive amination reaction with a compound represented by general formula (III'H) or a salt thereof to obtain a compound represented by general formula (III') or a medicamentable salt thereof, in which m3 is 1, 2 or 3; Among them, m6 is 0, 1 or 2; Z 4 is N, Z 5 is CH, A, J 1 , J 5 , X 2 , R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 3 , Z 6 , x, x1, y and y1 are as defined in general formula (III').

[0230] Another aspect of the present disclosure relates to a method for preparing a compound of general formula (X) or a medicamentable salt thereof, comprising: [ka] The method comprises the step of subjecting a compound represented by general formula (IVA) or a salt thereof to a condensation reaction with a compound represented by general formula (XB) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to obtain a compound represented by general formula (X) or a medicamentable salt thereof, Among them, R 1a , R 3a , W 1 , W 2 , W 3, W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , h, i, u, v, x1, y1, m3 and A are as defined in general formula (X).

[0231] Another aspect of the present disclosure relates to a method for preparing a compound represented by general formula (X-1) or a medicamentable salt thereof, comprising: [ka] The method includes a step of subjecting a compound represented by general formula (IV-1A) or a salt thereof to a condensation reaction with a compound represented by general formula (XB) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to obtain a compound represented by general formula (X-1) or a medicamentable salt thereof, Among them, R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , h, i, u, v, x1, y1, m3 and A are as defined in general formula (X-1).

[0232] Another aspect of the present disclosure relates to a method for preparing a compound of general formula (X) or a medicamentable salt thereof, comprising: [ka] The method includes a step of subjecting a compound represented by general formula (XC) or a salt thereof to a reductive amination reaction with a compound represented by general formula (XF) or a salt thereof (preferably the hydrochloride and trifluoroacetate salts) to obtain a compound represented by general formula (X) or a medicamentable salt thereof, wherein m3 is 0; Alternatively, the method includes a step of subjecting a compound represented by general formula (XD) or a salt thereof to a reductive amination reaction with a compound represented by general formula (XF) or a salt thereof (preferably hydrochloride and trifluoroacetate) to obtain a compound represented by general formula (X) or a medicamentable salt thereof, in which m3 is 1, 2 or 3; Among them, m6 is 0, 1 or 2; Z 4 is CH, Z 5 is N, R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 6 , h, i, u, v, x1, y1 and A are as defined in general formula (X).

[0233] Another aspect of the present disclosure relates to a method for preparing a compound represented by general formula (X-1) or a medicamentable salt thereof, comprising: [ka] The method includes a step of subjecting a compound represented by general formula (X-1C) or a salt thereof to a reductive amination reaction with a compound represented by general formula (XF) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to obtain a compound represented by general formula (X-1) or a medicamentable salt thereof, wherein m3 is 0; Alternatively, the method includes a step of subjecting a compound represented by general formula (X-1D) or a salt thereof to a reductive amination reaction with a compound represented by general formula (XF) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to obtain a compound represented by general formula (X-1) or a medicamentable salt thereof, in which m3 is 1, 2 or 3; Among them, m6 is 0, 1 or 2; Z 4 is CH, Z 5 is N, R 1a , R3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 6 , h, i, u, v, x1, y1 and A are as defined in general formula (X-1).

[0234] Another aspect of the present disclosure relates to a method for preparing a compound of general formula (IV') or a medicamentable salt thereof, comprising: [ka] The method comprises the steps of: subjecting a compound represented by general formula (IVA) or a salt thereof to a condensation reaction with a compound represented by general formula (IVB') or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to obtain a compound represented by general formula (IV') or a medicamentous salt thereof; Among them, R 1a , Q 1 , Q 2 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV').

[0235] Another aspect of the present disclosure relates to a method for preparing a compound represented by general formula (IV'-1) or a medicamentable salt thereof, which comprises: [ka] The method comprises the steps of: subjecting a compound represented by general formula (IV-1A) or a salt thereof to a condensation reaction with a compound represented by general formula (IVB') or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to obtain a compound represented by general formula (IV'-1) or a medicamentable salt thereof; Among them, R 1a , Q 1 , Q 2 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV'-1).

[0236] Another aspect of the present disclosure relates to a method for preparing a compound represented by general formula (IV'-1-1) and general formula (IV'-1-2) or a medicamentable salt thereof, which comprises: [ka] The method comprises the steps of: subjecting a compound represented by general formula (IV'-1) or a medicamentous salt thereof to chiral resolution to obtain a compound represented by general formula (IV'-1-1) and a compound represented by general formula (IV'-1-2) or a medicamentous salt thereof; Among them, R 1a , Q 1 , Q 2 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV'-1).

[0237] Another aspect of the present disclosure relates to a method for preparing a compound of general formula (M) or a medicamentable salt thereof, comprising: [ka] The method comprises the steps of: subjecting a compound represented by general formula (IVA) or a salt thereof to a condensation reaction with a compound represented by general formula (MB) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to obtain a compound represented by general formula (M) or a medicamentous salt thereof; Among them, R 1a , Q 1 , Q 2 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (M).

[0238] Another aspect of the present disclosure relates to a method for preparing a compound represented by general formula (M-1) or a medicamentable salt thereof, comprising: [ka] The method comprises the steps of: subjecting a compound represented by general formula (IV-1A) or a salt thereof to a condensation reaction with a compound represented by general formula (MB) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to obtain a compound represented by general formula (M-1) or a medicamentous salt thereof; Among them, R 1a , Q 1 , Q 2 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (M-1).

[0239] Another aspect of the present disclosure relates to a method for preparing a compound represented by general formula (M-1-1) and general formula (M-1-2) or a medicamentable salt thereof, which comprises: [ka] The method includes subjecting a compound represented by general formula (M-1) or a medicamentous salt thereof to chiral resolution to obtain a compound represented by general formula (M-1-1) and a compound represented by general formula (M-1-2) or a medicamentous salt thereof, Among them, R 1a , Q 1 , Q 2 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (M-1).

[0240] Another aspect of the present disclosure relates to a method for preparing a compound of general formula (IV) or a medicamentable salt thereof, comprising: [ka] The method comprises the steps of: subjecting a compound represented by general formula (IVA) or a salt thereof to a condensation reaction with a compound represented by general formula (IVB) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to obtain a compound represented by general formula (IV) or a medicamentous salt thereof; Among them, R 1a , Q 1 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2, Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV).

[0241] Another aspect of the present disclosure relates to a method for preparing a compound represented by general formula (IV-1) or a medicamentable salt thereof, comprising: [ka] The method comprises the steps of: subjecting a compound represented by general formula (IV-1A) or a salt thereof to a condensation reaction with a compound represented by general formula (IVB) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to obtain a compound represented by general formula (IV-1) or a medicamentable salt thereof; Among them, R 1a , Q 1 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV-1).

[0242] Another aspect of the present disclosure relates to a method for preparing a compound represented by general formula (IV-1-1) and general formula (IV-1-2) or a medicamentable salt thereof, which comprises: [ka] The method comprises the steps of: subjecting a compound represented by general formula (IV-1) or a medicamentous salt thereof to chiral resolution to obtain compounds represented by general formula (IV-1-1) and general formula (IV-1-2) or a medicamentous salt thereof; Among them, R 1a , Q 1 , Q 3 , Q 4 , Q5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV-1).

[0243] Another aspect of the present disclosure relates to a method for preparing a compound of general formula (V) or a medicamentable salt thereof, comprising: [ka] The method includes subjecting a compound represented by general formula (VA) or a salt thereof (preferably hydrochloride and trifluoroacetate) to a reductive amination reaction with a compound represented by general formula (VB) or a salt thereof to obtain a compound represented by general formula (V) or a medicamentable salt thereof, wherein m3 is 0; Alternatively, a compound represented by general formula (VA) or a salt thereof (preferably hydrochloride and trifluoroacetate) is subjected to a reductive amination reaction with a compound represented by general formula (VB') or a salt thereof to obtain a compound represented by general formula (V) or a medicamentable salt thereof, in which m3 is 1, 2 or 3; Among them, m6 is 0, 1 or 2; J 1 , R 1a , Q 1 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 3 , Z 6 , x, x1, y and y1 are as defined in general formula (V).

[0244] Another aspect of the present disclosure relates to a method for preparing a compound represented by general formula (V-1) or a medicamentable salt thereof, comprising: [ka] The method includes subjecting a compound represented by general formula (V-1A) or a salt thereof (preferably hydrochloride and trifluoroacetate) to a reductive amination reaction with a compound represented by general formula (VB) or a salt thereof to obtain a compound represented by general formula (V-1) or a medicamentable salt thereof, in which m3 is 0; Alternatively, a compound represented by general formula (V-1A) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) is subjected to a reductive amination reaction with a compound represented by general formula (VB') or a salt thereof to obtain a compound represented by general formula (V-1) or a medicamentable salt thereof, in which m3 is 1, 2 or 3; Among them, m6 is 0, 1 or 2; J 1 , R 1a , Q 1 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 3 , Z 6 , x, x1, y and y1 are as defined in general formula (V-1).

[0245] Another aspect of the present disclosure relates to a method for preparing a compound represented by general formula (V-1-1) and general formula (V-1-2) or a medicamentable salt thereof, which comprises: [ka] The method includes subjecting a compound represented by general formula (V-1) or a medicamentous salt thereof to chiral resolution to obtain compounds represented by general formula (V-1-1) and general formula (V-1-2) or a medicamentous salt thereof, Among them, J 1, R 1a , Q 1 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 3 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (V-1).

[0246] Another aspect of the present disclosure relates to a method for preparing a compound of general formula (VI) or a medicamentable salt thereof, comprising: [ka] The method comprises the steps of: subjecting a compound represented by general formula (VIA) or a salt thereof to a condensation reaction with a compound represented by general formula (VIB) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to obtain a compound represented by general formula (VI) or a medicamentable salt thereof; Among them, R 1a , R 3d , R 3e , R 3f , W 4 , Z 4 , Z 5 , x, x1, y, y1, m3 and Q 4 is as defined in general formula (VI).

[0247] Another aspect of the present disclosure relates to a method for preparing a compound represented by general formula (VI-1) or a medicamentable salt thereof, which comprises: [ka] The method comprises the steps of: subjecting a compound represented by general formula (VI-1A) or a salt thereof to a condensation reaction with a compound represented by general formula (VIB) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to obtain a compound represented by general formula (VI-1) or a medicamentable salt thereof; Among them, R1a , R 3d , R 3e , R 3f , W 4 , Z 4 , Z 5 , x, x1, y, y1, m3 and Q 4 is as defined in general formula (VI-1).

[0248] Another aspect of the present disclosure relates to a method for preparing a compound represented by general formula (VI-1-1) and general formula (VI-1-2) or a medicamentable salt thereof, which comprises: [ka] The method includes subjecting a compound represented by general formula (VI-1) or a medicamentous salt thereof to chiral resolution to obtain compounds represented by general formula (VI-1-1) and general formula (VI-1-2) or a medicamentous salt thereof, Among them, R 1a , R 3d , R 3e , R 3f , W 4 , Z 4 , Z 5 , x, x1, y, y1, m3 and Q 4 is as defined in general formula (VI-1).

[0249] Another aspect of the present disclosure relates to a method for preparing a compound of general formula (VII) or a medicamentable salt thereof, comprising the steps of: [ka] The method includes subjecting a compound represented by general formula (VIIA) or a salt thereof (preferably hydrochloride and trifluoroacetate) to a reductive amination reaction with a compound represented by general formula (VIIB) or a salt thereof to obtain a compound represented by general formula (VII) or a medicamentable salt thereof, wherein m3 is 0; Alternatively, a compound represented by general formula (VIIA) or a salt thereof (preferably hydrochloride and trifluoroacetate) is subjected to a reductive amination reaction with a compound represented by general formula (VIIB') or a salt thereof to obtain a compound represented by general formula (VII) or a medicamentable salt thereof, in which m3 is 1, 2 or 3; Among them, m6 is 0, 1 or 2; R 1a , Q 4 , R 3d , R 3e , R 3f , W 4 , x, x1, y and y1 are as defined in general formula (VII).

[0250] Another aspect of the present disclosure relates to a method for preparing a compound represented by general formula (VII-1) or a medicamentable salt thereof, comprising the steps of: [ka] The method includes subjecting a compound represented by general formula (VII-1A) or a salt thereof (preferably hydrochloride and trifluoroacetate) to a reductive amination reaction with a compound represented by general formula (VIIB) or a salt thereof to obtain a compound represented by general formula (VII-1) or a medicamentable salt thereof, wherein m3 is 0; Alternatively, a compound represented by general formula (VII-1A) or a salt thereof (preferably hydrochloride and trifluoroacetate) is subjected to a reductive amination reaction with a compound represented by general formula (VIIB') or a salt thereof to obtain a compound represented by general formula (VII-1) or a medicamentable salt thereof, in which m3 is 1, 2 or 3; Among them, m6 is 0, 1 or 2; R 1a , Q 4 , R 3d , R 3e , R 3f , W 4 , x, x1, y and y1 are as defined in general formula (VII-1).

[0251] Another aspect of the present disclosure relates to a method for preparing a compound represented by general formula (VII-1-1) and general formula (VII-1-2) or a medicamentable salt thereof, which comprises: [ka] The method comprises the steps of: chiral resolution of a compound represented by general formula (VII-1) or a medicamentous salt thereof to obtain compounds represented by general formula (VII-1-1) and general formula (VII-1-2) or a medicamentous salt thereof; Among them, R 1a , Q 4 , R 3d , R 3e , R 3f , W 4 , m3, x, x1, y and y1 are as defined in general formula (VII-1).

[0252] Another aspect of the present disclosure is a compound represented by the general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), The present invention relates to a pharmaceutical composition comprising a compound represented by general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1), general formula (V-1-2), general formula (VI), general formula (VI-1), general formula (VI-1-1), general formula (VI-1-2), general formula (VII), general formula (VII-1), general formula (VII-1-1) and general formula (VII-1-2) or a compound represented by Table A or a medicamentable salt thereof, and one or more pharma- ceutically acceptable vectors, diluents or excipients.

[0253] The present disclosure further relates to the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (I The present invention relates to the use of a compound represented by general formula (V), general formula (V-1), general formula (V-1-1), general formula (V-1-2), general formula (VI), general formula (VI-1), general formula (VI-1-1), general formula (VI-1-2), general formula (VII), general formula (VII-1), general formula (VII-1-1), general formula (VII-1-2) or Table A or a medicament salt thereof, or a pharmaceutical composition containing the same, in the preparation of a medicament for regulating the ubiquitination and degradation of the androgen receptor (AR) protein in a subject.

[0254] The present disclosure further relates to the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1 ... ), general formula (V-1-2), general formula (VI), general formula (VI-1), general formula (VI-1-1), general formula (VI-1-2), general formula (VII), general formula (VII-1), general formula (VII-1-1), general formula (VII-1-2) or Table A, or a pharmaceutical salt thereof, or a pharmaceutical composition containing the same, in the preparation of a medicament for treating and / or preventing an androgen receptor-mediated or dependent disease or condition, wherein the androgen receptor-mediated or dependent disease or condition is preferably selected from tumors, male sexual dysfunction and Kennedy's disease, more preferably selected from prostate cancer, prostatic hyperplasia, hirsutism, alopecia, anorexia nervosa, breast cancer, acne, male sexual dysfunction, Kennedy's disease and AIDS, most preferably prostate cancer, and even more preferably hormone-sensitive prostate cancer or hormone-refractory prostate cancer.

[0255] The present disclosure further relates to the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula The present invention relates to a compound represented by formula (IV-1-1), formula (IV-1-2), formula (V), formula (V-1), formula (V-1-1), formula (V-1-2), formula (VI), formula (VI-1), formula (VI-1-1), formula (VI-1-2), formula (VII), formula (VII-1), formula (VII-1-1), formula (VII-1-2) or Table A, or a medicinal salt thereof, or a pharmaceutical composition containing the same, for the treatment of tumors, male sexual dysfunction and Kennedy's disease. The present invention relates to the use of a compound of the present invention in the preparation of a medicament for the treatment and / or prevention of a comorbid condition, preferably in the preparation of a medicament for the treatment and / or prevention of prostate cancer, benign prostatic hyperplasia, hirsutism, alopecia, anorexia nervosa, breast cancer, acne, male sexual dysfunction, Kennedy's disease and AIDS, more preferably in the preparation of a medicament for the treatment and / or prevention of prostate cancer, and most preferably in the preparation of a medicament for the treatment and / or prevention of hormone-sensitive prostate cancer or hormone-refractory prostate cancer.

[0256] The present disclosure further relates to a method for regulating ubiquitination and degradation of androgen receptor (AR) protein in a subject, comprising administering to a patient in need thereof a therapeutically effective amount of any one of the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-2), general formula (M-3), general formula (M-4), general formula (M-5), general formula (M-6), general formula (M-7), general formula (M-8), general formula (M-9), general formula (M-10), general formula (M-11), general formula (M-12), general formula (M-13), general formula (M-14), general formula (M-15), general formula (M-16), general formula (M-17), general formula (M-18), general formula (M-19), general formula (M-20), general formula (M-21), general formula (M-22), general formula (M-23), general formula (M-24), general formula (M-25), general formula (M-26), general formula (M-27), general formula (M-28), general formula (M-29), general formula (M-30), general formula (M-31), general formula (M-32), general formula (M-33), general formula (M-34), general formula (M-35), general formula (M-36), general formula (M-37), general formula (M-38), general formula (M-39), general formula (M-40), general formula (M-41), general formula (M-42), general formula (M-43), general formula (M-44), general formula (M-45), general formula The method includes administering a compound represented by formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1), general formula (V-1-2), general formula (VI), general formula (VI-1), general formula (VI-1-1), general formula (VI-1-2), general formula (VII), general formula (VII-1), general formula (VII-1-1), general formula (VII-1-2) or Table A, or a medicamentable salt thereof, or a pharmaceutical composition containing the same.

[0257] The present disclosure further relates to a method for treating and / or preventing an androgen receptor mediated or dependent disease or condition, comprising administering to a patient in need thereof a therapeutically effective amount of the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (I androgen receptor mediated or dependent diseases or conditions include, for example, administering to the patient a compound of formula (IV-1-1), formula (IV-1-2), formula (V), formula (V-1), formula (V-1-1), formula (V-1-2), formula (VI), formula (VI-1), formula (VI-1-1), formula (VI-1-2), formula (VII), formula (VII-1), formula (VII-1-1), formula (VII-1-2) or a compound of formula (VII-1-3), formula (VII-1-4), formula (VII-1-5), formula (VII-1-6), formula (VII-1-7), formula (VII-1-8), formula (VII-1-9), formula (VII-20), formula (VII-21), formula (VII-22), formula (VII-23), formula (VII-24), formula (VII-25), formula (VII-26), formula (VII-27), formula (VII-28), formula (VII-29), formula (VII-30), formula (VII-31), formula (VII-32), formula (VII-33), formula (VII-34), formula (VII-35), formula (VII-36), formula (VII-37), formula (VII-38), formula (VII-39 ... The prostate cancer is preferably selected from prostate cancer, benign prostatic hyperplasia, hirsutism, alopecia, anorexia nervosa, breast cancer, acne, male sexual dysfunction, Kennedy's disease and AIDS, and is most preferably prostate cancer, and is most preferably hormone-sensitive prostate cancer or hormone-refractory prostate cancer.

[0258] The present disclosure further relates to the treatment of tumors, male sexual dysfunction and Kennedy's disease. The present invention relates to a method for treating and / or preventing a pulmonary circulation disease, which comprises administering to a patient in need thereof a therapeutically effective amount of the compound of formula (I), formula (II), formula (II-1), formula (G), formula (G-1), formula (III'), formula (III'-1), formula (III), formula (III-1), formula (X), formula (X-1), formula (IV'), formula (IV'-1), formula (IV'-1-1), formula (IV'-1-2), formula (M), formula (M-1), formula (M-1-1), formula (M-1-2), formula (IV), formula (IV-1), formula (IV-1-1), formula (IV-1-2), formula (V), formula (V-1), formula (V-1-1), The present invention relates to a method for treating and / or preventing a disease, comprising administering a compound represented by general formula (V-1-2), general formula (VI), general formula (VI-1), general formula (VI-1-1), general formula (VI-1-2), general formula (VII), general formula (VII-1), general formula (VII-1-1), general formula (VII-1-2) or Table A, or a medicinal salt thereof, or a pharmaceutical composition containing the same, and the method is preferably for treating and / or preventing prostate cancer, benign prostatic hyperplasia, hirsutism, alopecia, anorexia nervosa, breast cancer, acne, male sexual dysfunction, Kennedy's disease and AIDS, more preferably for treating and / or preventing prostate cancer, and most preferably for treating and / or preventing hormone-sensitive prostate cancer or hormone-refractory prostate cancer.

[0259] The present disclosure further relates to the compounds of the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (M-3), general formula (M-4), general formula (M-5), general formula (M-6), general formula (M-7), general formula (M-8), general formula (M-9), general formula (M-10), general formula (M-11), general formula (M-12), general formula (M-13), general formula (M-14), general formula (M-15), general formula (M-16), general formula (M-17), general formula (M-18), general formula (M-19), general formula (M-20), general formula (M-21), general formula (M-22), general formula (M-23), general formula (M-24), general formula (M-25), general formula (M-26), general formula (M-27), general formula (M-28), general formula (M-29), general formula (M-30), general formula (M-31), general formula (M-32), general formula (M-33), general formula (M-34), general formula (M-35), general formula (M-36), general formula (M-37), general formula (M-38), general formula (M-39 ... The present invention relates to a compound represented by formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1), general formula (V-1-2), general formula (VI), general formula (VI-1), general formula (VI-1-1), general formula (VI-1-2), general formula (VII), general formula (VII-1), general formula (VII-1-1), general formula (VII-1-2) or Table A, or a medicamentable salt thereof, or a pharmaceutical composition containing the same.

[0260] The present disclosure further relates to a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1), general formula (M-2), general formula (M-3), general formula (M-4), general formula (M-5), general formula (M-6), general formula (M-7), general formula (M-8), general formula (M-9), general formula (M-10), general formula (M-11), general formula (M-12), general formula (M-13), general formula (M-14), general formula (M-15), general formula (M-16), general formula (M-17), general formula (M-18), general formula (M-19), general formula (M-20), general formula (M-21), general formula (M-22), general formula (M-23), general formula (M-24), general formula (M-25), general formula (M-26), general formula (M-27), general formula (M-28), general formula (M-29), general formula (M-30), general formula (M-31), general formula (M-32), general formula (M-33), general formula (M-34), general formula (M-35), general formula (M-36), general formula (M-37), general formula (M-38), general formula (M-39 ... The present invention relates to a compound represented by formula (I-1-1), formula (M-1-2), formula (IV), formula (IV-1), formula (IV-1-1), formula (IV-1-2), formula (V), formula (V-1), formula (V-1-1), formula (V-1-2), formula (VI), formula (VI-1), formula (VI-1-1), formula (VI-1-2), formula (VII), formula (VII-1), formula (VII-1-1), formula (VII-1-2) or Table A, or a medicamentable salt thereof, or a pharmaceutical composition containing the same.

[0261] The present disclosure further relates to the above-mentioned general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1 ), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1), general formula (V-1-2), general formula (VI), general formula (VI-1), general formula (VI-1-1), general formula (VI-1-2), general formula (VII), general formula (VII-1), general formula (VII-1-1), general formula (VII-1-2) or a compound represented by Table A or a medicamentous salt thereof, or a pharmaceutical composition containing the same, wherein the androgen receptor mediated or dependent disease or condition is preferably tumor, male sexual dysfunction and Kennedy's disease. The prostate cancer is preferably selected from prostate cancer, benign prostatic hyperplasia, hirsutism, alopecia, anorexia nervosa, breast cancer, acne, male sexual dysfunction, Kennedy's disease and AIDS, and is most preferably prostate cancer, and is most preferably hormone-sensitive prostate cancer or hormone-refractory prostate cancer.

[0262] The present disclosure further relates to a compound of the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV) for use as a medicament for treating and / or preventing tumors, male sexual dysfunction and Kennedy's disease, preferably prostate cancer, prostatic hyperplasia, hirsutism, alopecia, anorexia nervosa, breast cancer, acne, male sexual dysfunction, Kennedy's disease and AIDS, more preferably prostate cancer, most preferably hormone-sensitive prostate cancer or hormone-refractory prostate cancer. The present invention relates to a compound represented by formula (IV'-1-1), formula (IV'-1-2), formula (M), formula (M-1), formula (M-1-1), formula (M-1-2), formula (IV), formula (IV-1), formula (IV-1-1), formula (IV-1-2), formula (V), formula (V-1), formula (V-1-1), formula (V-1-2), formula (VI), formula (VI-1), formula (VI-1-1), formula (VI-1-2), formula (VII), formula (VII-1), formula (VII-1-1), formula (VII-1-2) or Table A, or a medicamentable salt thereof, or a pharmaceutical composition containing the same.

[0263] The present disclosure further relates to a compound according to the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1 ... ), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1), general formula (V-1-2), general formula (VI), general formula (VI-1), general formula (VI-1-1), general formula (VI-1-2), general formula (VII), general formula (VII-1), general formula (VII-1-1), general formula (VII-1-2) or a compound represented by Table A, or a medicamentable salt thereof, or a pharmaceutical composition containing the same.

[0264] The present disclosure further relates to a compound represented by the general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-2), general formula (IV-3), general formula (IV-4), general formula (IV-5), general formula (IV-6), general formula (IV-7), general formula (IV-8), general formula (IV-9), general formula (IV-10), general formula (IV-11), general formula (IV-12), general formula (IV-13), general formula (IV-14), general formula (IV-15), general formula (IV-16), general formula (IV-17), general formula (IV-18), general formula (IV-19), general formula (IV-21), general formula (IV-22), general formula (IV-23), general formula (IV-24), general formula (IV-25), general formula (IV-26), general formula (IV-27), general formula (IV-28), general formula (IV-29 ... The present invention relates to a compound represented by formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1), general formula (V-1-2), general formula (VI), general formula (VI-1), general formula (VI-1-1), general formula (VI-1-2), general formula (VII), general formula (VII-1), general formula (VII-1-1), general formula (VII-1-2) or Table A, or a medicamentable salt thereof, or a pharmaceutical composition containing the same, wherein the androgen receptor mediated or dependent disease or condition is preferably tumor, male sexual dysfunction and Kennedy's disease. The prostate cancer is preferably selected from prostate cancer, benign prostatic hyperplasia, hirsutism, alopecia, anorexia nervosa, breast cancer, acne, male sexual dysfunction, Kennedy's disease and AIDS, and is most preferably prostate cancer, and is most preferably hormone-sensitive prostate cancer or hormone-refractory prostate cancer.

[0265] The present disclosure further relates to a compound represented by the above general formula (I), general formula (II), general formula (II-1), general formula (G), general formula (G-1), general formula (III'), general formula (III'-1), general formula (III), general formula (III-1), general formula (X), general formula (X-1), general formula (IV'), general formula (IV'-1), general formula (IV'-1-, general formula (IV'-1-) for treating and / or preventing tumors, male sexual dysfunction and Kennedy's disease, preferably prostate cancer, prostatic hyperplasia, hirsutism, alopecia, anorexia nervosa, breast cancer, acne, male sexual dysfunction, Kennedy's disease and AIDS, more preferably prostate cancer, most preferably hormone-sensitive prostate cancer or hormone-refractory prostate cancer. 1), general formula (IV'-1-2), general formula (M), general formula (M-1), general formula (M-1-1), general formula (M-1-2), general formula (IV), general formula (IV-1), general formula (IV-1-1), general formula (IV-1-2), general formula (V), general formula (V-1), general formula (V-1-1), general formula (V-1-2), general formula (VI), general formula (VI-1), general formula (VI-1-1), general formula (VI-1-2), general formula (VII), general formula (VII-1), general formula (VII-1-1), general formula (VII-1-2) or a compound represented by Table A, or a medicamentable salt thereof, or a pharmaceutical composition containing the same.

[0266] In certain embodiments, the disease or condition is asthma, multiple sclerosis, cancer, Kennedy's disease, ciliary disease, cleft palate, diabetes, heart disease, hypertension, inflammatory bowel disease, mental retardation, emotional disorders, obesity, refractive errors, infertility, Angelman's syndrome, Canavan disease, celiac disease, Charcot-Marie-Tooth disease, cystic fibrosis, Duchenne muscular dystrophy, hemochromatosis, hemophilia, Klinefelter's syndrome, neurofibroma, phenylketonuria, polycystic kidney disease, (PKD1) or 4 (PKD2) Prader-Willi syndrome, sickle cell disease, Tay-Sachs disease, Turner syndrome. Among these, the above cancers are squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, hepatocellular carcinoma, renal cell carcinoma, bladder cancer, intestinal cancer, breast cancer, cervical cancer, colon cancer, esophageal cancer, head cancer, kidney cancer, liver cancer, lung cancer, neck cancer, ovarian cancer, pancreatic cancer, prostate cancer, gastric cancer, leukemia, benign and malignant lymphoma (especially Burkitt's lymphoma and non-Hodgkin's lymphoma), benign and malignant melanoma, myeloproliferative disorders, sarcoma (including uterine cancer), and pulmonary sarcoma (including pulmonary sarcoma). In some embodiments, the disease being treated is cancer, such as Lewing's sarcoma, angiosarcoma, Kaposi's sarcoma, liposarcoma, myosarcoma, peripheral neuroepithelioma, synovial sarcoma, glioma, astrocytoma, oligodendroglioma, ependymoma, glioblastoma, neuroblastoma, ganglioneuroma, ganglioglioma, medulloblastoma, pinealocytoma, meningioma, meningeal sarcoma, neurofibroma, and schwannoma), endometrial cancer, testicular cancer, thyroid cancer, carcinosarcoma, Hodgkin's disease, Wilms' tumor, or teratocarcinoma. In some embodiments, the disease being treated is cancer, such as prostate cancer or Kennedy's disease.

[0267] The active compound may be in a form suitable for administration by any suitable route, and preferably the active compound is in a unit dose form or in a form that the patient can administer to himself / herself as a single dose. The unit dose presentation of the compound or composition of the present disclosure may be a tablet, capsule, cachet, bottled drug solution, drug powder, granules, topical tablet, suppository, reconstituted powder or liquid formulation.

[0268] As a general guideline, a suitable unit dose may be from 0.1 to 1000 mg.

[0269] The pharmaceutical composition according to the present disclosure may contain one or more additives in addition to the active compound, and the additives are selected from components such as fillers (diluents), binders, wetting agents, disintegrants, or excipients. The composition may contain 0.1 to 99% by weight of the active compound, depending on the method of administration.

[0270] The pharmaceutical composition containing the active ingredient may be in a form suitable for oral administration, such as tablets, dragees, tablets for external application, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs. Oral compositions may be prepared according to any method known in the art for preparing pharmaceutical compositions, and such compositions may contain one or more ingredients selected from sweeteners, flavorings, coloring agents, and preservatives, so as to provide a visually and palatably pleasing pharmaceutical preparation. Tablets contain the active ingredient and non-toxic medicament-acceptable excipients suitable for mixing in the preparation of tablets. These excipients may be inert excipients, granulating agents, disintegrating agents, binding agents, and lubricants. These tablets may be uncoated or may be coated by known techniques to mask the taste of the drug or to delay disintegration and absorption in the gastrointestinal tract, thereby providing a sustained release effect over a long period of time.

[0271] Oral formulations may be provided by soft gelatin capsules in which the active ingredient is mixed with an inert solid diluent, or with a water-soluble vector or oil-based solvent.

[0272] Aqueous suspensions contain the active substances and mixing excipients suitable for the preparation of aqueous suspensions. Such excipients are suspending, dispersing or wetting agents. Aqueous suspensions may also contain one or more preservatives, one or more coloring agents, one or more flavoring agents and one or more sweetening agents.

[0273] Oil suspensions can be prepared by suspending the active ingredient in vegetable oil or mineral oil.Oil suspensions can also contain thickening agents.To provide a palatable preparation, the above-mentioned sweeteners and flavorings can also be added.These compositions can be preserved by adding antioxidants.

[0274] The pharmaceutical compositions according to the present disclosure may be in the form of oil-in-water emulsions. The oil phase may be a vegetable oil, a mineral oil, or a mixture thereof. Suitable emulsifiers may be naturally occurring phospholipids, and the emulsion may contain sweeteners, flavoring agents, preservatives, and antioxidants. Such formulations may also contain demulcents, preservatives, colorants, and antioxidants.

[0275] The pharmaceutical compositions of the present disclosure may be in the form of a sterile injectable aqueous solution. Acceptable solvents or vehicles that can be used include water, Ringer's solution, and isotonic sodium chloride solution. The sterile injectable formulation may be a sterile injectable oil-in-water microemulsion in which the active ingredient is dissolved in the oil phase, and the injectable solution or microemulsion can be injected into the patient's bloodstream by local injection of large amounts. Alternatively, it is preferable to administer the solutions and microemulsions in a manner that allows a constant cyclic concentration of the compounds of the present disclosure to be maintained. To maintain such a constant concentration, a continuous intravenous administration device can be used. An example of such a device is the Deltec CADD-PLUS.TM. 5400 intravenous pump.

[0276] The pharmaceutical composition according to the present disclosure may be in the form of a sterile injectable aqueous or oily suspension for intramuscular and subcutaneous administration. The suspension may be prepared using a suitable dispersing or wetting agent and suspending agent according to known techniques. The sterile injectable preparation may be a sterile injectable solution or suspension prepared in a non-toxic diluent or solvent that is parenterally acceptable. Sterile fixed oils may also be conveniently used as a solvent or suspension medium. Any fixed oil for formulation may be used for this purpose. Fatty acids may also be used to prepare an injectable.

[0277] The compounds of the present disclosure may be administered in the form of suppositories for rectal administration. These pharmaceutical compositions can be prepared by mixing the drug with a suitable non-irritating excipient that is solid at room temperature but liquid in the rectum, and therefore melts in the rectum to release the drug.

[0278] As is well known to those skilled in the art, the dosage of a drug depends on many factors, including but not limited to the activity of the specific compound used, the patient's age, the patient's weight, the patient's physical condition, the patient's behavior, the patient's diet, the administration time, the administration method, the excretion rate, the composition of the drug, the severity of the disease, etc., and the optimal treatment method, such as the treatment mode, the daily dosage of the compound or the type of medicinal salt, can be verified according to conventional treatment plans.

[0279] Explanation of terms Unless specifically stated to the contrary, terms used in the specification and claims have the following meanings.

[0280] The term “alkyl group” refers to a saturated, straight or branched chain aliphatic hydrocarbon group having 1 to 20 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) carbon atoms (i.e., C 1-20 The alkyl group is an alkyl group having 1 to 12 carbon atoms (i.e., C 1-12 alkyl group) is preferred, and alkyl groups having 1 to 6 carbon atoms (i.e., C 1-6Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 6-methylhexyl, 7-methylhexyl, 8-methylhexyl, 9-methylhexyl, 10-methylhexyl, 11-methylhexyl, 12-methylhexyl, 13-methylhexyl, 14-methylhexyl, 15-methylhexyl, 16-methylhexyl, 17-methylhexyl, 18-methylhexyl, 19-methylhexyl, 22-methylhexyl, 23-methylhexyl, 24-methylhexyl, 25-methylhexyl, 26-methylhexyl, 27-methylhexyl, 28-methylhexyl, 29-methylhexyl, 30-methylhexyl, 31-methylhexyl, 32-methylhexyl, 33-methylhexyl, 34-methylhexyl, 35-methylhexyl, 36-methylhexyl, 37-methylhexyl, 38-methylhexyl, 39-methylhexyl, 40-methylhexyl, 41-methylhexyl, 42-methylhexyl, 43-methylhexyl, 44-methylhexyl, 45-methylhex Examples of such groups include 2,3-dimethylpentyl, 2,4-dimethylpentyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 2-ethylpentyl, 3-ethylpentyl, n-octyl, 2,3-dimethylhexyl, 2,4-dimethylhexyl, 2,5-dimethylhexyl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 4,4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl, n-nonyl, 2-methyl-2-ethylhexyl, 2-methyl-3-ethylhexyl, 2,2-diethylpentyl, n-decyl, 3,3-diethylhexyl, 2,2-diethylhexyl, and various branched chain isomers thereof. The alkyl group may be substituted or unsubstituted and, when substituted, it may be substituted at any available attachment point, and the substituents are preferably one or more selected from D atoms, halogens, alkoxy groups, haloalkyl groups, haloalkoxy groups, cycloalkyloxy groups, heterocyclyloxy groups, hydroxy groups, hydroxyalkyl groups, cyano groups, amino groups, nitro groups, cycloalkyl groups, heterocyclyl groups, aryl groups and heteroaryl groups.

[0281] The term "alkenyl group" refers to an alkyl group, the molecule of which contains at least one carbon-carbon double bond, where alkyl is as defined above, and has from 2 to 12 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12) carbon atoms (i.e., C 2-12 The alkenyl group is an alkenyl group having 2 to 6 carbon atoms (i.e., C 2-6 Alkenyl groups are preferred. Non-limiting examples include vinyl, propenyl, isopropenyl, butenyl, etc. The alkenyl group may be substituted or unsubstituted, and if substituted, it may be substituted at any available point of attachment, and the substituents are preferably one or more selected from D atoms, alkoxy groups, halogens, haloalkyl groups, haloalkoxy groups, cycloalkyloxy groups, heterocyclyloxy groups, hydroxy groups, hydroxyalkyl groups, cyano groups, amino groups, nitro groups, cycloalkyl groups, heterocyclyl groups, aryl groups, and heteroaryl groups.

[0282] The term "alkynyl group" refers to an alkyl group containing at least one carbon-carbon triple bond in the molecule, where alkyl is as defined above, and having from 2 to 12 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12) carbon atoms (i.e., C 2-12 The alkynyl group is an alkynyl group having 2 to 6 carbon atoms (i.e., C 2-6 Alkynyl groups are preferred. Non-limiting examples include ethynyl, propynyl, butynyl, pentynyl, hexynyl, etc. The alkynyl group may be substituted or unsubstituted, and if substituted, it may be substituted at any available point of attachment, and the substituents are preferably one or more selected from D atoms, alkoxy groups, halogens, haloalkyl groups, haloalkoxy groups, cycloalkyloxy groups, heterocyclyloxy groups, hydroxy groups, hydroxyalkyl groups, cyano groups, amino groups, nitro groups, cycloalkyl groups, heterocyclyl groups, aryl groups, and heteroaryl groups.

[0283] The term "alkoxy group" refers to -O-(alkyl group), where alkyl group is defined above. Non-limiting examples include methoxy, ethoxy, propoxy and butoxy groups. The alkoxy group may be substituted or unsubstituted, and if substituted, it may be substituted at any available attachment point, and the substituent is preferably one or more selected from D atom, halogen, alkoxy group, haloalkyl group, haloalkoxy group, cycloalkyloxy group, heterocyclyloxy group, hydroxy group, hydroxyalkyl group, cyano group, amino group, nitro group, cycloalkyl group, heterocyclyl group, aryl group and heteroaryl group.

[0284] The term "cycloalkyl group" refers to a saturated or partially unsaturated monocyclic all-carbocyclic ring (i.e., a monocyclic cycloalkyl group) or polycyclic ring system (i.e., a polycyclic cycloalkyl group) having 3 to 20 (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) ring atoms (i.e., a 3- to 20-membered cycloalkyl group). The cycloalkyl group is preferably a cycloalkyl group having 3 to 12 ring atoms (i.e., a 3- to 12-membered cycloalkyl group), more preferably a cycloalkyl group having 3 to 8 ring atoms (i.e., a 3- to 8-membered cycloalkyl group), and most preferably a cycloalkyl group having 3 to 6 ring atoms (i.e., a 3- to 6-membered cycloalkyl group).

[0285] The monocyclic cycloalkyl groups include, by way of non-limiting example, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, and cyclooctyl groups.

[0286] The polycyclic cycloalkyl groups include spirocycloalkyl groups, fused cycloalkyl groups and bridged cycloalkyl groups.

[0287] The term "spirocycloalkyl group" refers to a polycyclic ring system in which the rings share one carbon atom (referred to as a spiro atom), which may contain one or more double bonds within the ring, or which may contain one or more heteroatoms within the ring selected from nitrogen, oxygen and sulfur (which may optionally be oxidized, i.e., to form nitrogen oxides, and which may optionally be substituted with an oxo group, i.e., to form sulfoxides or sulfones, but which do not include -OO-, -OS- or -SS-), provided that at least one all-carbocyclic ring is included and the point of attachment is at the all-carbocyclic ring, which has from 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20) ring atoms (i.e., a 5-20 membered spirocycloalkyl group). The spirocycloalkyl group is preferably a spirocycloalkyl group having 6 to 14 ring atoms (i.e., a 6- to 14-membered spirocycloalkyl group), more preferably a spirocycloalkyl group having 7 to 10 ring atoms (i.e., a 7- to 10-membered spirocycloalkyl group). The spirocycloalkyl group includes a monospirocycloalkyl group and a polyspirocycloalkyl group (e.g., a bisspirocycloalkyl group, etc.), preferably a monospirocycloalkyl group or a bisspirocycloalkyl group, more preferably a 3-membered / 4-membered, 3-membered / 5-membered, 3-membered / 6-membered, 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 3-membered, 5-membered / 4-membered, 5-membered / 5-membered, 5-membered / 6-membered, 5-membered / 7-membered, 6-membered / 3-membered, 6-membered / 4-membered, 6-membered / 5-membered, 6-membered / 6-membered, 6-membered / 7-membered, 7-membered / 5-membered, or 7-membered / 6-membered monospirocycloalkyl group. Non-limiting examples are: The connection point may be located anywhere. [ka] etc.

[0288] The term "fused cycloalkyl group" refers to a polycyclic ring system in which the rings share two adjacent carbon atoms, such as a monocyclic cycloalkyl group fused to one or more monocyclic cycloalkyl groups, or a monocyclic cycloalkyl group fused to one or more heterocyclyl, aryl, or heteroaryl groups, where the point of attachment is on the monocyclic cycloalkyl group, which may contain one or more double bonds within the ring, and has 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) ring atoms (i.e., a 5-20 membered fused cycloalkyl group). The fused cycloalkyl group is preferably a fused cycloalkyl group having 6 to 14 ring atoms (i.e., a 6-14 membered fused cycloalkyl group), and more preferably a fused cycloalkyl group having 7 to 10 ring atoms (i.e., a 7-10 membered fused cycloalkyl group). The fused cycloalkyl group includes bicyclic fused cycloalkyl groups and polycyclic fused cycloalkyl groups (e.g., tricyclic fused cycloalkyl groups, tetracyclic fused cycloalkyl groups, etc.), preferably bicyclic fused cycloalkyl groups or tricyclic fused cycloalkyl groups, more preferably 3-membered / 4-membered, 3-membered / 5-membered, 3-membered / 6-membered, 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 3-membered, 5-membered / 4-membered, 5-membered / 5-membered, 5-membered / 6-membered, 5-membered / 7-membered, 6-membered / 3-membered, 6-membered / 4-membered, 6-membered / 5-membered, 6-membered / 6-membered, 6-membered / 7-membered, 7-membered / 5-membered, or 7-membered / 6-membered bicyclic fused cycloalkyl groups. Non-limiting examples are: The connection point may be located anywhere. [ka] etc.

[0289] The term "bridged cycloalkyl group" refers to an all-carbon polycyclic ring system in which the rings share two carbon atoms that are not directly connected to each other, and may contain one or more double bonds in the ring, and has 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) carbon atoms (i.e., a 5-20 membered bridged cycloalkyl group). The bridged cycloalkyl group is preferably a bridged cycloalkyl group having 6 to 14 carbon atoms (i.e., a 6-14 membered bridged cycloalkyl group), and more preferably a bridged cycloalkyl group having 7 to 10 carbon atoms (i.e., a 7-10 membered bridged cycloalkyl group). The bridged cycloalkyl group includes a bicyclic bridged cycloalkyl group and a polycyclic bridged cycloalkyl group (e.g., a tricyclic bridged cycloalkyl group, a tetracyclic bridged cycloalkyl group, etc.), and is preferably a bicyclic bridged cycloalkyl group or a tricyclic bridged cycloalkyl group. Non-limiting examples are: The connection point may be located anywhere. [ka] Includes.

[0290] The cycloalkyl group may be substituted or unsubstituted and, when substituted, it may be substituted at any available attachment point, and the substituents are preferably one or more selected from D atoms, halogens, alkyl groups, alkoxy groups, haloalkyl groups, haloalkoxy groups, cycloalkyloxy groups, heterocyclyloxy groups, hydroxy groups, hydroxyalkyl groups, oxo groups, cyano groups, amino groups, nitro groups, cycloalkyl groups, heterocyclyl groups, aryl groups and heteroaryl groups.

[0291] The term "heterocyclyl group" refers to a saturated or partially unsaturated monocyclic heterocycle (i.e., a monocyclic heterocyclyl group) or polycyclic heterocyclic ring system (i.e., a polycyclic heterocyclyl group) containing at least one (e.g., 1, 2, 3 or 4) heteroatom selected from nitrogen, oxygen and sulfur within the ring (wherein the nitrogen may be optionally oxidized, i.e., to form a nitrogen oxide, and the sulfur may be optionally substituted with an oxo group, i.e., to form a sulfoxide or sulfone, but does not include -OO-, -OS- or -SS-) and having 3 to 20 (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20) ring atoms (i.e., a 3- to 20-membered heterocyclyl group). The heterocyclyl group is preferably a heterocyclyl group having 3 to 12 ring atoms (i.e., a 3- to 12-membered heterocyclyl group), more preferably a heterocyclyl group having 3 to 8 ring atoms (i.e., a 3- to 8-membered heterocyclyl group), still more preferably a heterocyclyl group having 3 to 6 ring atoms (i.e., a 3- to 6-membered heterocyclyl group) or a heterocyclyl group having 4 to 6 ring atoms (i.e., a 4- to 6-membered heterocyclyl group), and most preferably a heterocyclyl group having 5 or 6 ring atoms (i.e., a 5- or 6-membered heterocyclyl group).

[0292] The monocyclic heterocyclyl groups include, by way of non-limiting example, pyrrolidinyl, tetrahydropyranyl, 1,2,3,6-tetrahydropyridyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, and homopiperazinyl groups.

[0293] The polycyclic heterocyclyl groups include spiroheterocyclyl groups, fused heterocyclyl groups and bridged heterocyclyl groups.

[0294] The term "spiroheterocyclyl group" refers to a polycyclic heterocyclic ring system in which the rings share one atom (referred to as a spiro atom), optionally containing one or more double bonds within the ring, and containing at least one (e.g., 1, 2, 3 or 4) heteroatoms selected from nitrogen, oxygen and sulfur within the ring (wherein the nitrogen may be optionally oxidized, i.e., to form a nitrogen oxide, and the sulfur may be optionally substituted with an oxo group, i.e., to form a sulfoxide or sulfone, but does not include -OO-, -OS- or -SS-), provided that at least one monocyclic heterocyclyl group is included and the point of attachment is at the monocyclic heterocyclyl group having 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20) ring atoms (i.e., a 5-20 membered spiroheterocyclyl group). The spiroheterocyclyl group is preferably a spiroheterocyclyl group having 6 to 14 ring atoms (i.e., a 6- to 14-membered spiroheterocyclyl group), more preferably a spiroheterocyclyl group having 7 to 11 ring atoms (i.e., a 7- to 11-membered spiroheterocyclyl group), and even more preferably a spiroheterocyclyl group having 7 to 10 ring atoms (i.e., a 7- to 10-membered spiroheterocyclyl group) or a spiroheterocyclyl group having 9 to 11 ring atoms (i.e., a 9- to 11-membered spiroheterocyclyl group). The spiroheterocyclyl group includes monospiroheterocyclyl groups and polyspiroheterocyclyl groups (such as bisspiroheterocyclyl groups), preferably monospiroheterocyclyl groups or bisspiroheterocyclyl groups, more preferably 3-membered / 4-membered, 3-membered / 5-membered, 3-membered / 6-membered, 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 3-membered, 5-membered / 4-membered, 5-membered / 5-membered, 5-membered / 6-membered, 5-membered / 7-membered, 6-membered / 3-membered, 6-membered / 4-membered, 6-membered / 5-membered, 6-membered / 6-membered, 6-membered / 7-membered, 7-membered / 5-membered or 7-membered / 6-membered monospiroheterocyclyl groups. Non-limiting examples are: [ka] etc.

[0295] The term "fused heterocyclyl group" refers to a polycyclic heterocyclic ring system in which the rings share two adjacent atoms, optionally containing one or more double bonds within the ring, and containing at least one (e.g., 1, 2, 3 or 4) heteroatoms selected from nitrogen, oxygen and sulfur within the ring, wherein the nitrogen may be optionally oxidized, i.e., to form a nitrogen oxide, and the sulfur may be optionally substituted with an oxo group, i.e., to form a sulfoxide or sulfone, but not limited to -OO-, -OS- or -SS-. (excluding) which is a monocyclic heterocyclyl group fused with one or more monocyclic heterocyclyl groups, or a monocyclic heterocyclyl group fused with one or more cycloalkyl groups, aryl groups, or heteroaryl groups, where the linking point is on the monocyclic heterocyclyl group and has 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20) ring atoms (i.e., a 5-20 membered fused heterocyclyl group). The above fused heterocyclyl group is preferably a fused heterocyclyl group having 6 to 14 ring atoms (i.e., a 6-14 membered fused heterocyclyl group), and more preferably a fused heterocyclyl group having 7 to 10 ring atoms (i.e., a 7-10 membered fused heterocyclyl group). The fused heterocyclyl groups include bicyclic and polycyclic fused heterocyclyl groups (e.g., tricyclic fused heterocyclyl groups, tetracyclic fused heterocyclyl groups, etc.), preferably bicyclic fused heterocyclyl groups or tricyclic fused heterocyclyl groups, more preferably 3-membered / 4-membered, 3-membered / 5-membered, 3-membered / 6-membered, 4-membered / 4-membered, 4-membered / 5-membered, 4-membered / 6-membered, 5-membered / 3-membered, 5-membered / 4-membered, 5-membered / 5-membered, 5-membered / 6-membered, 5-membered / 7-membered, 6-membered / 3-membered, 6-membered / 4-membered, 6-membered / 5-membered, 6-membered / 6-membered, 6-membered / 7-membered, 7-membered / 5-membered or 7-membered / 6-membered bicyclic fused heterocyclyl groups. Non-limiting examples are: [ka] etc.

[0296] The term "bridged heterocyclyl group" refers to a polycyclic heterocyclic ring system in which the rings share two atoms that are not directly linked, which may contain one or more double bonds within the ring, and which contains at least one (e.g., 1, 2, 3 or 4) heteroatoms selected from nitrogen, oxygen and sulfur within the ring (which nitrogen may optionally be oxidized, i.e., to form a nitrogen oxide, and which sulfur may optionally be substituted with an oxo group, i.e., to form a sulfoxide or sulfone, but does not include -OO-, -OS- or -SS-) and which has 5 to 20 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20) ring atoms (i.e., a 5-20 membered bridged heterocyclyl group). The bridged heterocyclyl group is preferably a bridged heterocyclyl group having 6 to 14 ring atoms (i.e., a 6- to 14-membered bridged heterocyclyl group), and more preferably a bridged heterocyclyl group having 7 to 10 ring atoms (i.e., a 7- to 10-membered bridged heterocyclyl group). Depending on the number of rings constituting the heterocyclyl group, it can be divided into a bicyclic bridged heterocyclyl group and a polycyclic bridged heterocyclyl group (e.g., a tricyclic bridged heterocyclyl group, a tetracyclic bridged heterocyclyl group, etc.), and is preferably a bicyclic bridged heterocyclyl group or a tricyclic bridged heterocyclyl group. Non-limiting examples are: [ka] etc.

[0297] The heterocyclyl group may be substituted or unsubstituted and, when substituted, it may be substituted at any available attachment point, and the substituents are preferably one or more selected from D atoms, halogens, alkyl groups, alkoxy groups, haloalkyl groups, haloalkoxy groups, cycloalkyloxy groups, heterocyclyloxy groups, hydroxy groups, hydroxyalkyl groups, oxo groups, cyano groups, amino groups, nitro groups, cycloalkyl groups, heterocyclyl groups, aryl groups and heteroaryl groups.

[0298] The term "aryl group" refers to a monocyclic all-carbon aromatic ring (i.e., a monocyclic aryl group) or a polycyclic aromatic ring system (i.e., a polycyclic aryl group) having a conjugated π-electron system and having 6 to 14 (e.g., 6, 7, 8, 9, 10, 11, 12, 13, or 14) ring atoms (i.e., a 6-14-membered aryl group). The aryl group is preferably an aryl group having 6 to 10 ring atoms (i.e., a 6-10-membered aryl group). The monocyclic aryl group is, for example, a phenyl group. The polycyclic aryl group includes, as non-limiting examples, a naphthyl group, an anthryl group, a phenanthryl group, and the like. The polycyclic aryl groups further include those in which a phenyl group is fused to one or more of a heterocyclyl group or a cycloalkyl group, or a naphthyl group is fused to one or more of a heterocyclyl group or a cycloalkyl group, where the point of attachment is at the phenyl or naphthyl group, and in this case the number of ring atoms still indicates the number of ring atoms in the polycyclic aromatic ring system, non-limiting examples include: [ka] etc.

[0299] The aryl group may be substituted or unsubstituted and, when substituted, it may be substituted at any available attachment point, and the substituents are preferably one or more selected from D atoms, halogens, alkyl groups, alkoxy groups, haloalkyl groups, haloalkoxy groups, cycloalkyloxy groups, heterocyclyloxy groups, hydroxy groups, hydroxyalkyl groups, oxo groups, cyano groups, amino groups, nitro groups, cycloalkyl groups, heterocyclyl groups, aryl groups and heteroaryl groups.

[0300] The term "heteroaryl group" refers to a monocyclic heteroaromatic ring (i.e., a monocyclic heteroaryl group) or a polycyclic heteroaromatic ring system (i.e., a polycyclic heteroaryl group) having a conjugated π-electron system and containing at least one (e.g., 1, 2, 3, or 4) heteroatom selected from nitrogen, oxygen, and sulfur within the ring (which nitrogen may optionally be oxidized, i.e., to form a nitrogen oxide, and which sulfur may optionally be substituted with an oxo group, i.e., to form a sulfoxide or sulfone, but does not include -OO-, -OS-, or -SS-) and which has 5 to 14 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14) ring atoms (i.e., a 5-14 membered heteroaryl group). The heteroaryl group is preferably a heteroaryl group having 5 to 10 ring atoms (i.e., a 5- to 10-membered heteroaryl group), more preferably a heteroaryl group having 5 or 6 ring atoms (i.e., a 5- or 6-membered heteroaryl group), and most preferably a heteroaryl group having 6 ring atoms (i.e., a 6-membered heteroaryl group).

[0301] Non-limiting examples of the monocyclic heteroaryl group include a furanyl group, a thienyl group, a thiazolyl group, an isothiazolyl group, an oxazolyl group, an isoxazolyl group, an oxadiazolyl group, a thiadiazolyl group, an imidazolyl group, a pyrazolyl group, a triazolyl group, a tetrazolyl group, a furazanyl group, a pyrrolyl group, an N-alkylpyrrolyl group, a pyridyl group, a pyrimidinyl group, a pyridonyl group, an N-alkylpyridone (e.g., [ka] etc.), pyrazinyl group, pyridazinyl group, etc.

[0302] The polycyclic heteroaryl groups include, as non-limiting examples, indolyl, indazolyl, quinolyl, isoquinolyl, quinoxalyl, phthalazinyl, benzimidazolyl, benzothienyl, quinazolinyl, benzothiazolyl, carbazolyl, etc. The polycyclic heteroaryl groups further include monocyclic heteroaryl groups fused with one or more aryl groups, where the connection point is on the aromatic ring, and in this case the number of ring atoms still indicates the number of ring atoms in the polycyclic heteroaromatic ring system. The polycyclic heteroaryl groups further include monocyclic heteroaryl groups fused with one or more cycloalkyl or heterocyclyl groups, where the connection point is on the monocyclic heteroaromatic ring, and in this case the number of ring atoms still indicates the number of ring atoms in the polycyclic heteroaromatic ring system. Non-limiting examples are: [ka] etc.

[0303] The heteroaryl group may be substituted or unsubstituted and, when substituted, it may be substituted at any available point of attachment, and the substituents are preferably one or more selected from D atoms, halogens, alkyl groups, alkoxy groups, haloalkyl groups, haloalkoxy groups, cycloalkyloxy groups, heterocyclyloxy groups, hydroxy groups, hydroxyalkyl groups, cyano groups, amino groups, nitro groups, cycloalkyl groups, heterocyclyl groups, aryl groups and heteroaryl groups.

[0304] The term "amino-protecting group" refers to a group that is easily removed and introduced to an amino group so that the amino group is not altered when other parts of the molecule are reacted. Non-limiting examples include (trimethylsilyl)ethoxymethyl, tetrahydropyranyl, tert-butoxycarbonyl (Boc), benzyloxycarbonyl (Cbz), fluorenylmethyloxycarbonyl (Fmoc), allyloxycarbonyl (Alloc), trimethylsilylethoxycarbonyl (Teoc), methoxycarbonyl, ethoxycarbonyl, phthaloyl (Pht), p-toluenesulfonyl (Tos), trifluoroacetyl (Tfa), trityl (Trt), 2,4-dimethoxybenzyl (DMB), acetyl, benzyl, allyl, p-methoxybenzyl, and the like.

[0305] The term "hydroxy protecting group" refers to a labile group that is introduced into a hydroxy group to react with another functional group of a compound in order to block or protect the hydroxy group. Non-limiting examples include trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), tert-butyldimethylsilyl (TBS), tert-butyldiphenylsilyl (TBDPS), methyl, tert-butyl, allyl, benzyl, methoxymethyl (MOM), ethoxyethyl, 2-tetrahydropyranyl (THP), formyl, acetyl, benzoyl, p-nitrobenzoyl, and the like.

[0306] The term "spirocyclic group" refers to a spirocycloalkyl group or a spiroheterocyclyl group, wherein the spirocycloalkyl group and the spiroheterocyclyl group are as defined above.

[0307] The term "cycloalkylalkyl group" refers to an alkyl group substituted with one or more cycloalkyl groups, where the cycloalkyl group, alkyl group are as defined above.

[0308] The term "heterocyclylalkyl group" refers to an alkyl group substituted with one or more heterocyclyl groups, where the heterocyclyl group, alkyl group are as defined above.

[0309] The term "aminoalkyl group" refers to an alkyl group substituted with one or more amino groups, where the alkyl group is as defined above.

[0310] The term "alkoxyalkyl group" refers to an alkyl group substituted with one or more alkoxy groups, where the alkoxy and alkyl groups are as defined above.

[0311] The term "haloalkyl group" refers to an alkyl group substituted with one or more halogens, where the alkyl group is as defined above.

[0312] The term "haloalkoxy" refers to an alkoxy group substituted with one or more halogens, where alkoxy is as defined above.

[0313] The term "deuterated alkyl group" refers to an alkyl group substituted with one or more deuterium atoms, where the alkyl group is as defined above.

[0314] The term "hydroxyalkyl group" refers to an alkyl group substituted with one or more hydroxy groups, where alkyl is as defined above.

[0315] The term "halogen" refers to fluorine, chlorine, bromine or iodine.

[0316] The term "hydroxy group" refers to --OH.

[0317] The term "mercapto" refers to -SH.

[0318] The term "amino group" means -NH 2 Refers to...

[0319] The term "cyano" refers to -CN.

[0320] The term "nitro group" means -NO 2 Refers to...

[0321] The term "oxo" or "oxo group" refers to "=O".

[0322] The term "carbonyl group" refers to C=O.

[0323] The term "carboxy" refers to -C(O)OH.

[0324] The term "carboxylic acid ester group" refers to a -C(O)O(alkyl), -C(O)O(cycloalkyl), (alkyl)C(O)O-, or (cycloalkyl)C(O)O-, where the alkyl and cycloalkyl groups are defined above.

[0325] In this disclosure, when m1 is 0, X 2 is a bond.

[0326] In this disclosure, when m2 is 0, J 1 is a bond.

[0327] In this disclosure, when m3 is 0, J 3 is a bond.

[0328] In this disclosure, when m4 is 0, J 5 is a bond.

[0329] The term "ubiquitin ligase" refers to a family of proteins that facilitate the transfer of ubiquitin to specific substrate proteins and target the substrate proteins for degradation. For example, cereblon is an E3 ubiquitin ligase protein that, alone or in combination with an E2 ubiquitin conjugating enzyme, allows ubiquitin to be linked to lysines of target proteins and target specific protein substrates for degradation by the proteasome. Thus, the action of an E3 ubiquitin ligase alone or in combination with an E2 ubiquitin conjugating enzyme leads to the transfer of ubiquitin to a target protein. Generally, ubiquitin ligases are involved in polyubiquitination, such that a second ubiquitin is linked to the first ubiquitin, a third ubiquitin is linked to the second ubiquitin, and so on. Polyubiquitinated tagged proteins are for degradation by the proteasome. However, there are ubiquitination events that are limited to monoubiquitination, where only a single ubiquitin is added to the substrate molecule by ubiquitin ligase. Monoubiquitinated proteins are not targeted to the proteasome for degradation, but may instead be altered in their cellular location or function, for example by binding to other proteins that have a domain capable of binding ubiquitin. To further complicate matters, various lysines in ubiquitin can be targeted by E3 to prepare the chain. The most common lysine is Lys48 in the ubiquitin chain. It is the lysine to prepare polyubiquitin and is recognized by the proteasome.

[0330] The term "target protein" refers to proteins and peptides that have any biological function or activity, including structural, regulatory, hormonal, enzymatic, genetic, immune, contractile, storage, transport and signaling. In some embodiments, target proteins include structural proteins, receptors, enzymes, cell surface proteins, proteins associated with integral functions of cells, including proteins involved in catalytic activity, aromatase activity, motility activity, helicase activity, metabolic processes (anabolic and catabolic metabolism), antioxidant activity, protein hydrolysis, biosynthesis, proteins with kinase activity, oxidoreductase activity, transferase activity, hydrolase activity, lyase activity, isomerase activity, ligase activity, enzyme regulator activity, signal transduction factor activity, structural molecule activity, binding activity (proteins, lipids carbohydrates), receptor activity, cell motility, membrane fusion, cell communication, biological process regulation, development, cell differentiation, response to stimuli, behavioral proteins, cell adhesion proteins, proteins involved in cell death, proteins involved in transport (including protein transport activity, nuclear transport, ion transport activity, channel transport activity, vector activity), permease activity, secretion activity, electron transport activity, pathogen, accessory protein regulator activity, nucleic acid binding activity, transcription regulator activity, extracellular structural and biogenic activity, translation regulator activity. Such proteins include proteins from eukaryotes and prokaryotes, including microorganisms, viruses, fungi and parasites as well as many others, including humans, microorganisms, viruses, fungi and parasites as targets for drug therapy, other animals including livestock, microorganisms and other antimicrobials and plants as targets for antibiotics, as well as viruses and many others.

[0331] The compounds of the present disclosure may have specific stereoisomeric forms. The term "stereoisomer" refers to isomers that have the same structure but differ in the spatial arrangement of atoms. It includes cis and trans (or Z and E) isomers, (-)- and (+)-isomers, (R)- and (S)-enantiomers, diastereomers, (D)- and (L)-isomers, tautomers, atropisomers, conformers, and mixtures thereof (e.g., racemates, mixtures of diastereomers). Substituents in the compounds of the present disclosure may have other asymmetric atoms. All such stereoisomers and mixtures thereof are included within the scope of the present disclosure. Optically active (-)- and (+)-isomers, (R)- and (S)-enantiomers, and (D)- and (L)-isomers can be prepared by chiral synthesis, chiral reagents, or other conventional techniques. Single isomers of certain compounds of the present disclosure can be prepared by asymmetric synthesis or chiral auxiliaries, or, if the molecule contains a basic functional group (e.g., an amino group) or an acidic functional group (e.g., a carboxy group), by forming a diastereomeric salt with an appropriate optically active acid or base, and then performing diastereomeric resolution by conventional methods known in the art to obtain the pure isomers. Furthermore, separation of enantiomers and diastereomers is typically accomplished by chromatography.

[0332] In the chemical structures of the compounds described in this disclosure, [ka] indicates that the configuration is not specified, i.e., if chiral isomers are present in the chemical structure, [ka] The bond [ka] or [ka] Any carbon-carbon double bond may have both the Z and E configurations, even if only one configuration is named.

[0333] The compounds of the present disclosure may exist in different tautomeric forms, and all such forms are included within the scope of the present disclosure. The term "tautomer" or "tautomeric form" refers to a structural isomer that exists in equilibrium and in which the isomeric form is easily converted from one to the other. It includes all possible tautomers, i.e., exists in the form of a single isomer or in the form of a mixture of said tautomers in any ratio. Non-limiting examples include keto-enol, imine-enamine, lactam-lactim, etc. An example of lactam-lactim equilibrium is as follows: [ka]

[0334] For example, reference to a pyrazolyl group should be understood to include any one or a mixture of the two tautomers of the following two structures: [ka]

[0335] All tautomeric forms are within the scope of the disclosure, and the naming of a compound does not exclude any tautomeric form.

[0336] The compounds of the present disclosure may include atropisomers. The term "atropisomer" refers to conformational stereoisomers that are produced by inhibiting or greatly slowing down the rotation around a single bond in a molecule (due to spatial interactions with other parts of the molecule and the asymmetry of the substituents at both ends of the single bond), and whose tautomerization is slow enough to be separated and separated under certain conditions. For example, some compounds of the present disclosure may exist in the form of a mixture of atropisomers (e.g., an equal ratio mixture, a mixture enriched in one atropisomer, etc.) or in the form of purified atropisomers.

[0337] The compounds of the present disclosure include all suitable isotopic derivatives of the compounds. The term "isotopic derivative" refers to a compound in which at least one atom is replaced with an atom having the same atomic number but a different atomic mass. Examples of isotopes that can be introduced into the compounds of the present disclosure include stable and radioactive isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine, and iodine, for example, 2 H (deuterium, D), 3 H (deuterium, T), 11 C. 13 C. 14 C. 15 N, 17 O. 18 O. 32 P, 33 P, 33 S, 34 S, 35 S, 36 S, 18 F, 36 Cl, 82 Br, 123 I, 124 I, 125 I, 129 I and 131 I, with deuterium being preferred.

[0338] Compared with non-deuterated drugs, deuterated drugs have the advantages of reducing toxicity and side effects, increasing drug stability, improving therapeutic efficacy, and extending the biological half-life of drugs. All isotopic variations of the compounds according to the present disclosure, whether radioactive or not, are included within the scope of the present disclosure. Each available hydrogen atom connected to a carbon atom may be independently replaced with a deuterium atom, where deuterium replacement may be partial or complete, and partial deuterium replacement means that at least one hydrogen is replaced with at least one deuterium.

[0339] When a position is specifically designated as deuterium D, it is to be understood that the position is a deuterium having an abundance at least 1000 times greater than the natural abundance of deuterium, which is 0.015%, (i.e., at least 15% deuterium is incorporated). In the examples, a compound having an abundance greater than the natural abundance of deuterium includes at least 1000 times the abundance of deuterium (i.e., at least 15% of deuterium is incorporated), at least 2000 times the abundance of deuterium (i.e., at least 30% of deuterium is incorporated), at least 3000 times the abundance of deuterium (i.e., at least 45% of deuterium is incorporated), at least 3340 times the abundance of deuterium (i.e., at least 50.1% of deuterium is incorporated), at least 3500 times the abundance of deuterium (i.e., at least 52.5% of deuterium is incorporated), at least 4000 times the abundance of deuterium (i.e., at least 60% of deuterium is incorporated), at least 4500 times the abundance of deuterium (i.e., at least 67.5% of deuterium is incorporated), and the like. deuterium may be at least 5000 times abundant (i.e., at least 75% of the deuterium are incorporated), at least 5500 times abundant (i.e., at least 82.5% of the deuterium are incorporated), at least 6000 times abundant (i.e., at least 90% of the deuterium are incorporated), at least 6333.3 times abundant (i.e., at least 95% of the deuterium are incorporated), at least 6466.7 times abundant (i.e., at least 97% of the deuterium are incorporated), at least 6600 times abundant (i.e., at least 99% of the deuterium are incorporated), at least 6633.3 times abundant (i.e., at least 99.5% of the deuterium are incorporated) or more abundant.

[0340] "Optionally" or "optionally" means that the next described event or circumstance may or may not occur, and the description includes both cases where the event or circumstance occurs and where it does not occur. For example, "C optionally substituted with halogen or cyano groups" 1-6The "alkyl group" includes the case where the alkyl group is substituted with a halogen or a cyano group, and the case where the alkyl group is not substituted with a halogen or a cyano group.

[0341] "Substituted" or "substituted" refers to the replacement of one or more hydrogen atoms, preferably 1 to 6, more preferably 1 to 3 hydrogen atoms in a group, with a corresponding number of substituents, independently of one another. A person skilled in the art can determine (experimentally or theoretically) possible or impossible substitutions without much effort. For example, an amino group or a hydroxy group having free hydrogen may be unstable when bonded to a carbon atom having an unsaturated bond (e.g., an olefin).

[0342] "Pharmaceutical composition" refers to a mixture of one or more compounds described herein or their medicamentous salts with other chemical components, and other components such as pharmaceutical acceptable vectors and excipients. The pharmaceutical composition is intended to facilitate administration to a living body and contribute to the absorption of the active ingredient to further exert biological activity.

[0343] "Pharmaceutical salt" refers to a salt of a compound according to the present disclosure, which may be selected from inorganic salts or organic salts. Such salts have the desired biological activity while being safe and effective when used in a mammalian body. They may be prepared separately during the final isolation and purification process of the compound, or by reacting a suitable group with a suitable base or acid. In general, bases for forming pharmaceutical acceptable salts include inorganic bases such as sodium hydroxide and potassium hydroxide, and organic bases such as ammonium. In general, acids for forming pharmaceutical acceptable salts include inorganic acids and organic acids.

[0344] With respect to a drug or pharmacologically active agent, the term "therapeutically effective amount" refers to a dose of the drug or agent sufficient to obtain or at least partially obtain a desired effect. The therapeutically effective amount is determined by the person concerned and depends on the age and general condition of the recipient, and also on the specific active agent, but the appropriate therapeutically effective amount for an individual can be determined by one skilled in the art through routine testing.

[0345] As used herein, the term "pharmacologically acceptable" means that these compounds, materials, compositions and / or dosage forms are, within the scope of reasonable medical judgment, applicable for contact with the tissues of a patient without undue toxicity, irritation, allergic response or other problem or complication, and are effective for the desired use, with a reasonable benefit / risk ratio.

[0346] As used herein, the singular forms "a," "an," and "the" include plural references and vice versa unless the context clearly indicates otherwise.

[0347] The term "about" when applied to parameters such as pH, concentration, temperature, etc., indicates that the parameter in question may be varied within ±10%, and in some cases more preferably ±5%. As will be appreciated by those skilled in the art, when a parameter is not critical, generally numbers are given merely for illustration, not limitation.

[0348] Methods for synthesizing compounds according to the present disclosure In order to achieve the objectives of the present disclosure, the present disclosure adopts the following technical solutions:

[0349] Technical proposal 1 A method for preparing a compound of general formula (III') or a medicamentable salt thereof according to the present disclosure, comprising: [ka] The method includes the step of subjecting a compound represented by general formula (III'A) or a salt thereof and a compound represented by general formula (III'B) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to a condensation reaction in the presence of a condensing agent under basic conditions to obtain a compound represented by general formula (III') or a medicamentable salt thereof, Among them, J 1 is -C(O)-, Z 3 is N, A, R 1a , R 3a , J5 , X 2 , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (III').

[0350] Technical proposal 2 A method for preparing a compound of general formula (III') or a medicamentable salt thereof according to the present disclosure, comprising: [ka] The method includes a step of subjecting a compound represented by general formula (III'C) or a salt thereof and a compound represented by general formula (III'E) or a salt thereof (preferably hydrochloride and trifluoroacetate) to a reductive amination reaction in the presence of a reducing agent under weak acidic conditions to obtain a compound represented by general formula (III') or a medicamentable salt thereof, wherein m3 is 1, 2 or 3; Alternatively, the method includes a step of subjecting a compound represented by general formula (III'D) or a salt thereof and a compound represented by general formula (III'E) or a salt thereof (preferably hydrochloride and trifluoroacetate) to a reductive amination reaction in the presence of a reducing agent under weak acidic conditions to obtain a compound represented by general formula (III') or a medicamentable salt thereof, in which m3 is 0; Among them, m6 is 0, 1 or 2; Z 4 is CH, Z 5 is N, A, J 1 , J 5 , X 2 , R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 3 , Z6 , x, x1, y and y1 are as defined in general formula (III').

[0351] Technical proposal 3 A method for preparing a compound of general formula (III') or a medicamentable salt thereof according to the present disclosure, comprising: [ka] The method includes a step of subjecting a compound represented by general formula (III'F) or a salt thereof (preferably hydrochloride and trifluoroacetate) and a compound represented by general formula (III'G) or a salt thereof to a reductive amination reaction in the presence of a reducing agent under weak acidic conditions to obtain a compound represented by general formula (III') or a medicamentable salt thereof, wherein m3 is 0; Alternatively, the method includes a step of subjecting a compound represented by general formula (III'F) or a salt thereof (preferably hydrochloride and trifluoroacetate) and a compound represented by general formula (III'H) or a salt thereof to a reductive amination reaction in the presence of a reducing agent under weak acidic conditions to obtain a compound represented by general formula (III') or a medicamentable salt thereof, in which m3 is 1, 2 or 3; Among them, m6 is 0, 1 or 2; Z 4 is N, Z 5 is CH, A, J 1 , J 5 , X 2 , R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 3 , Z 6 , x, x1, y and y1 are as defined in general formula (III').

[0352] Technical proposal 4 A method for preparing a compound of general formula (X) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method comprises the steps of: subjecting a compound represented by general formula (IVA) or a salt thereof to a condensation reaction with a compound represented by general formula (XB) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) in the presence of a condensing agent under basic conditions to obtain a compound represented by general formula (X) or a medicamentable salt thereof; Among them, R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , h, i, u, v, x1, y1, m3 and A are as defined in general formula (X).

[0353] Technical proposal 5 A method for preparing a compound of general formula (X-1) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method includes a step of subjecting a compound represented by general formula (IV-1A) or a salt thereof and a compound represented by general formula (XB) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to a condensation reaction under basic conditions in the presence of a condensing agent to obtain a compound represented by general formula (X-1) or a medicamentable salt thereof, Among them, R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , h, i, u, v, x1, y1, m3 and A are as defined in general formula (X-1).

[0354] Technical plan 6 A method for preparing a compound of general formula (X) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method includes the step of subjecting a compound represented by general formula (XC) or a salt thereof and a compound represented by general formula (XF) or a salt thereof (preferably hydrochloride and trifluoroacetate) to a reductive amination reaction in the presence of a reducing agent under weak acidic conditions to obtain a compound represented by general formula (X) or a medicamentable salt thereof, wherein m3 is 0; Alternatively, the method includes a step of subjecting a compound represented by general formula (XD) or a salt thereof and a compound represented by general formula (XF) or a salt thereof (preferably hydrochloride and trifluoroacetate) to a reductive amination reaction in the presence of a reducing agent under weak acidic conditions to obtain a compound represented by general formula (X) or a medicamentable salt thereof, in which m3 is 1, 2 or 3; Among them, m6 is 0, 1 or 2; Z 4 is CH, Z 5 is N, R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 6 , h, i, u, v, x1, y1 and A are as defined in general formula (X).

[0355] Technical proposal 7 A method for preparing a compound of general formula (X-1) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method includes a step of subjecting a compound represented by general formula (X-1C) or a salt thereof and a compound represented by general formula (XF) or a salt thereof (preferably hydrochloride and trifluoroacetate) to a reductive amination reaction in the presence of a reducing agent under weak acidic conditions to obtain a compound represented by general formula (X-1) or a medicamentable salt thereof, wherein m3 is 0; Alternatively, the method includes a step of subjecting a compound represented by general formula (X-1D) or a salt thereof and a compound represented by general formula (XF) or a salt thereof (preferably hydrochloride and trifluoroacetate) to a reductive amination reaction in the presence of a reducing agent under weak acidic conditions to obtain a compound represented by general formula (X-1) or a medicamentable salt thereof, in which m3 is 1, 2 or 3; Among them, m6 is 0, 1 or 2; Z 4 is CH, Z 5 is N, R 1a , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 6 , h, i, u, v, x1, y1 and A are as defined in general formula (X-1).

[0356] Technical proposal 8 A method for preparing a compound of general formula (IV') or a medicamentable salt thereof according to the present disclosure, comprising: [ka] The method includes the step of subjecting a compound represented by general formula (IVA) or a salt thereof and a compound represented by general formula (IVB') or a salt thereof (preferably hydrochloride and trifluoroacetate) to a condensation reaction in the presence of a condensing agent under basic conditions to obtain a compound represented by general formula (IV') or a medicamentable salt thereof, Among them, R 1a , Q 1 , Q 2 , Q 3 , Q4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV').

[0357] Technical proposal 9 A method for preparing a compound of general formula (IV'-1) or a medicamentable salt thereof according to the present disclosure, comprising: [ka] The method includes the step of subjecting a compound represented by general formula (IV-1A) or a salt thereof and a compound represented by general formula (IVB') or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to a condensation reaction under basic conditions in the presence of a condensing agent to obtain a compound represented by general formula (IV'-1) or a medicamentable salt thereof, Among them, R 1a , Q 1 , Q 2 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV'-1).

[0358] Technical proposal 10 A method for preparing the compounds of the present disclosure represented by general formula (IV'-1-1) and general formula (IV'-1-2) or medicamentable salts thereof, comprising: [ka] The method includes a step of subjecting a compound represented by general formula (IV'-1) or a medicament salt thereof to chiral resolution to obtain a compound represented by general formula (IV'-1-1) and a compound represented by general formula (IV'-1-2) or a medicament salt thereof, Among them, R 1a , Q 1 , Q 2 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV'-1).

[0359] Technical proposal 11 A method for preparing a compound of general formula (M) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method comprises the steps of: subjecting a compound represented by general formula (IVA) or a salt thereof and a compound represented by general formula (MB) or a salt thereof (preferably hydrochloride and trifluoroacetate) to a condensation reaction in the presence of a condensing agent under basic conditions to obtain a compound represented by general formula (M) or a medicamentable salt thereof; Among them, R 1a , Q 1 , Q 2 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (M).

[0360] Technical proposal 12 A method for preparing a compound represented by general formula (M-1) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method includes the steps of: subjecting a compound represented by general formula (IV-1A) or a salt thereof and a compound represented by general formula (MB) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to a condensation reaction in the presence of a condensing agent under basic conditions to obtain a compound represented by general formula (M-1) or a medicamentable salt thereof; Among them, R 1a , Q 1 , Q 2 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (M-1).

[0361] Technical proposal 13 A method for preparing a compound represented by general formula (M-1-1) and general formula (M-1-2) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method includes a step of subjecting a compound represented by general formula (M-1) or a medicamentous salt thereof to chiral resolution to obtain a compound represented by general formula (M-1-1) and a compound represented by general formula (M-1-2) or a medicamentous salt thereof, Among them, R 1a , Q 1 , Q 2 , Q 4 , Q 5 , R 3a , W 1 , W2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (M-1).

[0362] Technical proposal 14 A process for preparing a compound of general formula (IV) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method includes the steps of: subjecting a compound represented by general formula (IVA) or a salt thereof to a condensation reaction with a compound represented by general formula (IVB) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) in the presence of a condensing agent under basic conditions to obtain a compound of general formula (IV) or a medicamentable salt thereof; Among them, R 1a , Q 1 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV).

[0363] Technical proposal 15 A method for preparing a compound of general formula (IV-1) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method includes the step of subjecting a compound represented by general formula (IV-1A) or a salt thereof and a compound represented by general formula (IVB) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to a condensation reaction in the presence of a condensing agent under basic conditions to obtain a compound represented by general formula (IV-1) or a medicamentable salt thereof, Among them, R 1a , Q 1 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV-1).

[0364] Technical proposal 16 A method for preparing a compound represented by general formula (IV-1-1) and general formula (IV-1-2) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method includes a step of subjecting a compound represented by general formula (IV-1) or a medicamentous salt thereof to chiral resolution to obtain a compound represented by general formula (IV-1-1) and a compound represented by general formula (IV-1-2) or a medicamentous salt thereof, Among them, R 1a , Q 1 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 4 , Z 5 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (IV-1).

[0365] Technical proposal 17 A process for preparing a compound of general formula (V) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method includes the steps of subjecting a compound represented by general formula (VA) or a salt thereof (preferably hydrochloride and trifluoroacetate) to a reductive amination reaction in the presence of a reducing agent under weak acidic conditions with a compound represented by general formula (V) or a medicamentable salt thereof, wherein m3 is 0; Alternatively, the method includes a step of subjecting a compound represented by general formula (VA) or a salt thereof (preferably hydrochloride and trifluoroacetate) and a compound represented by general formula (VB') or a salt thereof to a reductive amination reaction in the presence of a reducing agent under weak acidic conditions to obtain a compound represented by general formula (V) or a medicamentable salt thereof, wherein m3 is 1, 2 or 3; Among them, m6 is 0, 1 or 2; J 1 , R 1a , Q 1 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 3 , Z 6 , x, x1, y and y1 are as defined in general formula (V).

[0366] Technical proposal 18 A method for preparing a compound represented by general formula (V-1) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method includes a step of subjecting a compound represented by general formula (V-1A) or a salt thereof (preferably hydrochloride and trifluoroacetate) and a compound represented by general formula (VB) or a salt thereof to a reductive amination reaction in the presence of a reducing agent under weak acidic conditions to obtain a compound represented by general formula (V-1) or a medicamentable salt thereof, wherein m3 is 0; Alternatively, the method includes a step of subjecting a compound represented by general formula (V-1A) or a salt thereof (preferably hydrochloride and trifluoroacetate) and a compound represented by general formula (VB') or a salt thereof to a reductive amination reaction in the presence of a reducing agent under weak acidic conditions to obtain a compound represented by general formula (V-1) or a medicamentable salt thereof, in which m3 is 1, 2 or 3; Among them, m6 is 0, 1 or 2; J 1 , R 1a , Q 1 , Q 3 , Q 4 , Q 5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 3 , Z 6 , x, x1, y and y1 are as defined in general formula (V-1).

[0367] Technical proposal 19 A method for preparing a compound represented by general formula (V-1-1) and general formula (V-1-2) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method includes a step of subjecting a compound represented by general formula (V-1) or a medicamentous salt thereof to chiral resolution to obtain a compound represented by general formula (V-1-1) and a compound represented by general formula (V-1-2) or a medicamentous salt thereof, Among them, J 1 , R 1a , Q 1 , Q 3 , Q 4 , Q5 , R 3a , W 1 , W 2 , W 3 , W 4 , Z 1 , Z 2 , Z 3 , Z 6 , x, x1, y, y1 and m3 are as defined in general formula (V-1).

[0368] Technical proposal 20 A process for preparing a compound of general formula (VI) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method comprises the steps of: subjecting a compound represented by general formula (VIA) or a salt thereof to a condensation reaction with a compound represented by general formula (VIB) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) in the presence of a condensing agent under basic conditions to obtain a compound represented by general formula (VI) or a medicamentable salt thereof; Among them, R 1a , R 3d , R 3e , R 3f , W 4 , Z 4 , Z 5 , x, x1, y, y1, m3 and Q 4 is as defined in general formula (VI).

[0369] Technical proposal 21 A method for preparing a compound of general formula (VI-1) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method includes a step of subjecting a compound represented by general formula (VI-1A) or a salt thereof and a compound represented by general formula (VIB) or a salt thereof (preferably a hydrochloride and a trifluoroacetate) to a condensation reaction in the presence of a condensing agent under basic conditions to obtain a compound represented by general formula (VI-1) or a medicamentable salt thereof, Among them, R1a , R 3d , R 3e , R 3f , W 4 , Z 4 , Z 5 , x, x1, y, y1, m3 and Q 4 is as defined in general formula (VI-1).

[0370] Technical proposal 22 A method for preparing a compound represented by general formula (VI-1-1) and general formula (VI-1-2) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method includes a step of subjecting a compound represented by general formula (VI-1) or a medicamentous salt thereof to chiral resolution to obtain compounds represented by general formula (VI-1-1) and general formula (VI-1-2) or a medicamentous salt thereof, Among them, R 1a , R 3d , R 3e , R 3f , W 4 , Z 4 , Z 5 , x, x1, y, y1, m3 and Q 4 is as defined in general formula (VI-1).

[0371] Technical proposal 23 A process for preparing a compound of general formula (VII) and / or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method includes the steps of subjecting a compound represented by general formula (VIIA) or a salt thereof (preferably hydrochloride and trifluoroacetate) and a compound represented by general formula (VIIB) or a salt thereof to a reductive amination reaction in the presence of a reducing agent under weak acidic conditions to obtain a compound represented by general formula (VII) or a medicamentable salt thereof, wherein m3 is 0; Alternatively, the method includes a step of subjecting a compound represented by general formula (VIIA) or a salt thereof (preferably hydrochloride and trifluoroacetate) and a compound represented by general formula (VIIB') or a salt thereof to a reductive amination reaction in the presence of a reducing agent under weak acidic conditions to obtain a compound represented by general formula (VII) or a medicamentable salt thereof, wherein m3 is 1, 2 or 3; Among them, m6 is 0, 1 or 2; R 1a , Q 4 , R 3d , R 3e , R 3f , W 4 , x, x1, y and y1 are as defined in general formula (VII).

[0372] Technical proposal 24 A method for preparing a compound of general formula (VII-1) or a medicamentable salt thereof according to the present disclosure, comprising the steps of: [ka] The method includes a step of subjecting a compound represented by general formula (VII-1A) or a salt thereof (preferably hydrochloride and trifluoroacetate) and a compound represented by general formula (VIIB) or a salt thereof to a reductive amination reaction in the presence of a reducing agent under weak acidic conditions to obtain a compound represented by general formula (VII-1) or a medicamentable salt thereof, wherein m3 is 0; Alternatively, the method includes a step of subjecting a compound represented by general formula (VII-1A) or a salt thereof (preferably hydrochloride and trifluoroacetate) and a compound represented by general formula (VIIB') or a salt thereof to a reductive amination reaction in the presence of a reducing agent under weak acidic conditions to obtain a compound represented by general formula (VII-1) or a medicamentable salt thereof, in which m3 is 1, 2 or 3; Among them, m6 is 0, 1 or 2; R 1a , Q 4 , R 3d , R 3e , R 3f , W 4, x, x1, y and y1 are as defined in general formula (VII-1).

[0373] Technical proposal 25 A method for preparing the compounds of the present disclosure represented by general formula (VII-1-1) and general formula (VII-1-2) or a medicamentable salt thereof, comprising the steps of: [ka] The method includes a step of subjecting a compound represented by general formula (VII-1) or a medicament salt thereof to chiral resolution to obtain a compound represented by general formula (VII-1-1) and a compound represented by general formula (VII-1-2) or a medicament salt thereof, Among them, R 1a , Q 4 , R 3d , R 3e , R 3f , W 4 , m3, x, x1, y and y1 are as defined in general formula (VII-1).

[0374] In the above synthesis scheme, the condensing agent is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N'-dicyclohexylcarbodiimide, N,N'-diisopropylcarbodiimide, O-benzotriazole-N,N,N',N'-tetramethyluronium tetrafluoroborate, 1-hydroxybenzotriazole, 1-hydroxy-7-azobenzotriazole, O-benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate, O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium The condensing agent includes, but is not limited to, O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), 2-(7-benzotriazole oxide)-N,N,N',N'-tetramethyluronium hexafluorophosphate, benzotriazol-1-yloxytri(dimethylamino)phosphonium hexafluorophosphate or benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate, preferably, the condensing agent is O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU).

[0375] In the above synthesis scheme, the reagent providing basic conditions includes organic bases and inorganic bases, the organic bases include, but are not limited to, triethylamine, N,N-diisopropylethylamine, n-butyllithium, lithium diisopropylamide, potassium acetate, sodium acetate, sodium ethoxide, sodium tert-butoxide, or potassium tert-butoxide, and the inorganic bases include, but are not limited to, sodium hydride, potassium phosphate, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, lithium hydroxide monohydrate, lithium hydroxide, and potassium hydroxide, and preferably, the reagent providing basic conditions is N,N-diisopropylethylamine.

[0376] In the above synthesis scheme, the reagents that provide the weak acidic conditions are acetic acid, Ti(i-PrO) 3 and B.F. 3 Et2 Preferably, the agent providing the weakly acidic conditions is acetic acid, including, but not limited to, O; alternatively, the weakly acidic conditions are provided by an acid produced in the reaction, including, but not limited to, acetic acid (acetic acid).

[0377] In the above synthesis scheme, the reducing agent includes, but is not limited to, sodium triacetoxyborohydride, sodium borohydride, lithium borohydride, sodium cyanoborohydride, and sodium acetylborohydride, etc., preferably sodium cyanoborohydride and sodium triacetoxyborohydride.

[0378] The above synthesis scheme is preferably carried out in a solvent, and the solvents used include, but are not limited to, ethylene glycol dimethyl ether, acetic acid, methanol, ethanol, acetonitrile, n-butanol, toluene, tetrahydrofuran, dichloromethane, petroleum ether, ethyl acetate, n-hexane, dimethyl sulfoxide, 1,4-dioxane, water, N,N-dimethylformamide, N,N-dimethylacetamide, and mixtures thereof. [Brief description of the drawings]

[0379] [Figure 1] 1 shows the therapeutic effect of the compounds of Examples 15-1 and 11-2 or 11-1 (relatively long retention time) on LNCap-FGC transplanted tumors in castrated CB17-SCID mice. [Diagram 2] 1 shows the effect of the compounds of Examples 15-1 and 11-2 or 11-1 (relatively long retention time) on the body weight of CB17-SCID mice. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0380] The present disclosure will be further described below with reference to examples, but these examples are not intended to limit the scope of the present disclosure. EXAMPLES

[0381] The structure of the compound is determined by nuclear magnetic resonance (NMR) and / or mass spectrometry (MS). The NMR shifts (δ) are 10 -6 The unit of the concentration is expressed in ppm. The NMR measurement was performed using a nuclear magnetic resonance spectrometer Bruker AVANCE-400 or Bruker AVANCE NEO 500M, and the measurement solvent was deuterated dimethyl sulfoxide (DMSO-d 6 ), deuterated chloroform (CDCl 3 ), deuterated methanol (CD 3 OD) and the internal standard is tetramethylsilane (TMS).

[0382] For the MS measurements, a liquid chromatograph mass spectrometer Agilent 1200 / 1290 DAD-6110 / 6120 Quadrupole MS (manufacturer: Agilent, MS model number: 6110 / 6120 Quadrupole MS) was used.

[0383] Waters ACQuity UPLC-QD / SQD (Manufacturer: Waters, MS model number: Waters ACQuity Qda Detector / Waters SQ Detector) THERMO Ultimate 3000-Q Exactive (Manufacturer: THERMO, MS Model Number: THERMO Q Exactive) For high performance liquid chromatography (HPLC) analysis, high performance liquid chromatographs Agilent HPLC 1200DAD, Agilent HPLC 1200VWD and Waters HPLC e2695-2489 were used.

[0384] For chiral HPLC analysis, a high performance liquid chromatograph Agilent 1260 DAD was used.

[0385] For high-performance liquid preparative chromatography, preparative chromatographs Waters 2545-2767, Waters 2767-SQ Detecor2, Shimadzu LC-20AP and Gilson GX-281 were used.

[0386] For chiral separation, a preparative chromatograph Shimadzu LC-20AP was used.

[0387] Combiflash Rf200 (TELEDYNE ISCO) was used as the CombiFlash high-speed preparative chromatograph.

[0388] As the silica gel plate for thin layer chromatography, Yantai Yellow Sea HSGF254 or Qingdao GF254 silica gel plate is used, the specification of the silica gel plate used for thin layer chromatography (TLC) is 0.15-0.2 mm, and the specification for separating and purifying the product by thin layer chromatography is 0.4-0.5 mm.

[0389] For silica gel column chromatography, 200-300 mesh silica gel manufactured by Yantai Huanghai Silica Gel was generally used as the vector.

[0390] Kinase mean inhibition rate and IC 50 The values ​​were measured using a plate reader NovoStar (BMG, Germany).

[0391] Known starting materials according to the present disclosure may be synthesized by or according to methods known in the art, or may be purchased from companies such as ABCR GmbH & Co. KG, Acros Organics, Aldrich Chemical Company, Shaoyuan Chemical Technology (Accela ChemBio Inc.), and Darui Chemical.

[0392] In the examples, unless otherwise stated, all reactions can be carried out in an argon or nitrogen atmosphere.

[0393] An argon or nitrogen atmosphere refers to an argon or nitrogen balloon of approximately 1 L volume connected to the reaction flask.

[0394] Hydrogen atmosphere refers to a hydrogen balloon of approximately 1 L volume attached to the reaction flask.

[0395] For the pressurized hydrogenation reaction, a Parr 3916EKX hydrogenation apparatus and a Seiran QL-500 hydrogen generator or an HC2-SS hydrogenation apparatus were used.

[0396] The hydrogenation reaction was generally carried out by repeating the process of evacuating and refilling with hydrogen three times.

[0397] A CEM Discover-S 908860 microwave reactor was used for microwave reactions.

[0398] In the examples, unless otherwise specified, the solution refers to an aqueous solution.

[0399] In the examples, unless otherwise specified, the reaction temperature is room temperature, 20 to 30°C.

[0400] In the examples, thin layer chromatography (TLC) was used to monitor the progress of the reaction. The developing solvent used in the reaction, the eluent system of column chromatography for purifying the compound, and the developing solvent system of thin layer chromatography included A: dichloromethane / methanol system, B: n-hexane / ethyl acetate system, and the volume ratio of the solvents may be adjusted according to the polarity of the compound, and may be adjusted by adding a small amount of basic or acidic reagent such as triethylamine and acetic acid.

[0401] Example 1 4-(4-(1-(4-((S)-2-(3-chloro-4-cyanophenyl)-3-methyl-2,8-diazaspiro[4.5]dec-8-yl)benzoyl)piperidin-4-yl)piperazin-1-yl)-N-(2,6-dioxopiperidin-3-yl)-2-fluorobenzamide 1 (diastereomeric mixture) [ka] [ka]

[0402] Step 1 (±)-tert-Butyl 4-(4-((2,6-dioxopiperidin-3-yl)aminocarbonyl)-3-fluorophenyl)piperazine-1-carboxylate 1c Compound 4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-2-fluorobenzoic acid 1a (3.0 g, 9.25 mmol, prepared by the known method "ChemBioChem, 2014, 15 (8), 1111-1120") was dissolved in N,N-dimethylformamide (25 mL), followed by addition of O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (5.28 g, 13.87 mmol) and N,N-diisopropylethylamine (3.59 g, 27.75 mmol, 4.6 mL), and stirring for 10 minutes, followed by addition of (±)-3-aminopiperidine-2,6-dione hydrochloride 1b (1.83 g, 11.10 mmol, BiDe Pharmaceutical), and continued stirring for 2 hours. The reaction solution was added dropwise to water (30 mL), and then saturated saline (about 20 mL) was added to the water, filtered, and the filter cake was washed with water (40 mL). The filter cake was collected and dried under vacuum to obtain the title product 1c (3.8 g, yield: 95%).

[0403] Step 2 (±)-N-(2,6-dioxopiperidin-3-yl)-2-fluoro-4-(piperazin-1-yl)benzamide hydrochloride 1d Compound 1c (3.8 g, 8.75 mmol) was dissolved in dichloromethane (40 mL), 4 M hydrogen chloride in 1,4-dioxane (17.5 mL) was added, the reaction was stirred for 2 h, filtered, and the filter cake was stirred in 50 mL of a mixed solvent of ethyl acetate and methanol (V / V=20:1), and the process was repeated twice to give title compound 1d (2.53 g, yield: 78%). MS m / z (ESI): 335.1 [M+1].

[0404] Step 3 (±)-tert-Butyl 4-(4-(4-((2,6-dioxopiperidin-3-yl)aminocarbonyl)-3-fluorophenyl)piperazin-1-yl)piperidine-1-carboxylate 1f In a 25mL three-neck flask, dichloromethane (5mL), methanol (1mL), compound 1d (80mg, 0.21mmol) were added in that order, anhydrous sodium acetate (89mg, 1.08mmol) was added, and the mixture was stirred for 15 minutes. Acetic acid (26mg, 0.43mmol), 4-oxopiperidine-1-carboxylate tert-butyl 1e (86mg, 0.43mmol, BiDe Pharmaceutical) were added, and the mixture was stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (92mg, 0.43mmol) was slowly added, and the mixture was reacted for 16 hours. Compound 1e (344mg, 1.73mmol) and sodium triacetoxyborohydride (92mg, 0.43mmol) were then added, and the mixture was heated to 40℃, and the mixture was allowed to react for 12 hours. While cooling with an ice bath, 10 mL of saturated sodium bicarbonate solution was added into the system to quench the reaction, and the mixture was extracted with dichloromethane (20 mL×3), the organic phases were combined and washed with saturated sodium chloride solution (20 mL×3), the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography with eluent system A to obtain the title compound 1f (65 mg, yield: 58%). MS m / z (ESI): 518.8 [M+1].

[0405] Step 4 (±)-N-(2,6-dioxopiperidin-3-yl)-2-fluoro-4-(4-(piperidin-4-yl)piperazin-1-yl)benzamide dihydrochloride 1g Compound 1f (80 mg, 0.15 mmol) was dissolved in dichloromethane (3 mL), and 4 M hydrogen chloride in 1,4-dioxane solution (1.1 mL) was slowly added under ice bath, and the mixture was reacted for 3 hours. The reaction solution was concentrated under reduced pressure and dried under vacuum to obtain the title compound 1g (75 mg, yield: 100%) as a crude product, which was used in the next reaction without purification. MS m / z (ESI): 418.3 [M+1].

[0406] Step 5 4-(4-(1-(4-((S)-2-(3-chloro-4-cyanophenyl)-3-methyl-2,8-diazaspiro[4.5]dec-8-yl)benzoyl)piperidin-4-yl)piperazin-1-yl)-N-(2,6-dioxopiperidin-3-yl)-2-fluorobenzamide 1 (diastereomeric mixture) In a 25 mL three-neck flask, N,N-dimethylformamide (2 mL), compound 1g (50 mg, 0.10 mmol), compound (S)-4-(2-(3-chloro-4-cyanophenyl)-3-methyl-2,8-diazaspiro[4.5]dec-8-yl)benzoic acid 1h (50 mg, 0.078 mmol, prepared by the method disclosed in the patent application "Example 10 on page 211 of the specification in WO2021055756A1") were added in order, and N,N-diisopropylethylamine (102 mg, 0.79 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (60 mg, 0.16 mmol) were slowly added under ice bath, and the system was heated to room temperature and reacted for 16 hours. The reaction solution was filtered and separated and purified by high-performance liquid preparative chromatography (Waters 2545, elution system: 10 mmol / L aqueous ammonium bicarbonate solution and acetonitrile, acetonitrile gradient: 36% to 51%, flow rate: 30 mL / min) to obtain the title compound 1 (diastereomeric mixture, ratio 1:1, 26 mg, yield: 41%). MS m / z (ESI): 809.3 [M+1]. 1 H NMR (500 MHz, DMSO-d 6): δ 10.84 (s, 1H), 8.04 (t, 1H), 7.72-7.52 (m, 2H), 7.26 (d, 2H), 6.95 (d, 2H), 6.87-6.72 (m, 3H), 6.66 (d, 1H), 4.78-4.64 (m, 1H), 4.34-3.92 (m, 3H), 3.52-3.42 (m, 2H), 3.40-3.34 (m, 2H), 3.29-3.12 (m, 5H), 3.02-2.71 (m, 5H), 2.68-2.54 (m, 4H), 2.28-2.18 (m, 1H), 2.10-2.05 (m, 1H), 2.04-1.96 (m, 1H), 1.90-1.66 (m, 4H), 1.64-1.55 (m, 1H), 1.53-1.44 (m, 2H), 1.42-1.32 (m, 2H), 1.30-1.13 (m, 4H).

[0407] Example 2 5-(4-(1-(4-((S)-2-(3-chloro-4-cyanophenyl)-3-methyl-2,8-diazaspiro[4.5]dec-8-yl)benzoyl)piperidin-4-yl)piperazin-1-yl)-N-(2,6-dioxopiperidin-3-yl)pyridinecarboxamide 2 (diastereomeric mixture) [ka] [ka] Step 1 (±)-tert-butyl 4-(6-((2,6-dioxopiperidin-3-yl)aminocarbonyl)pyridin-3-yl)piperazine-1-carboxylate 2b In a 100 mL three-neck flask, N,N-dimethylformamide (30 mL), 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)picolinic acid 2a (2.9 g, 9.44 mmol, prepared by the method disclosed in the patent application "WO2012003189A1, page 95, Example 21"), compound 1b (1.86 g, 11.32 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (5.38 g, 14.14 mmol), and triethylamine (2.86 g, 28.31 mmol) were added in this order, and the mixture was stirred at room temperature for 1 hour. Water (20 mL) was added to the system, and the mixture was extracted with ethyl acetate (50 mL x 3). The organic phases were combined, washed with saturated sodium chloride solution (20 mL x 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was stirred in 50 mL of a mixed solvent of n-heptane and ethyl acetate (V / V = 20:1), filtered, and the filter cake was collected to obtain the title compound 2b (2.9 g, yield: 74%).

[0408] Step 2 (±)-N-(2,6-dioxopiperidin-3-yl)-5-(piperazin-1-yl)pyridinecarboxamide dihydrochloride 2c Compound 2b (2.9 g, 6.95 mmol) was dissolved in dichloromethane (60 mL), 4 M hydrogen chloride in 1,4-dioxane (30 mL) was added, and the mixture was stirred at room temperature for 3 hours. After filtration, the filter cake was washed with dichloromethane (5 mL) and ethyl acetate (5 mL) in that order, and dried under vacuum to give the title compound 2c (2.7 g, yield: 100%). MS m / z (ESI): 318.1 [M+1].

[0409] Step 3 (±)-4-(4-(6-((2,6-dioxopiperidin-3-yl)aminocarbonyl)pyridin-3-yl)piperazin-1-yl)piperidine-1-carboxylate tert-Butyl ester 2d Dichloromethane (5mL), methanol (1mL), and compound 2c (80mg, 0.20mmol) were added in this order to a 25mL three-neck flask, and anhydrous sodium acetate (93mg, 1.13mmol) was added and stirred for 15 minutes. Acetic acid (28mg, 0.47mmol) and compound 1e (90mg, 0.45mmol) were added, and the mixture was stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (96mg, 0.45mmol) was slowly added and the mixture was reacted for 16 hours. Compound 1e (360mg, 1.80mmol) and sodium triacetoxyborohydride (96mg, 0.45mmol) were added again, and the mixture was heated to 40°C and allowed to react for 12 hours. While cooling with an ice bath, 10 mL of saturated sodium bicarbonate solution was added into the system to quench the reaction, and the mixture was extracted with dichloromethane (20 mL×3), the organic phases were combined and washed with saturated sodium chloride solution (20 mL×3), the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography with eluent system A to obtain the title compound 2d (63 mg, yield: 63%). MS m / z (ESI): 501.5 [M+1].

[0410] Step 4 (±)-N-(2,6-dioxopiperidin-3-yl)-5-(4-(piperidin-4-yl)piperazin-1-yl)pyridinecarboxamide trihydrochloride 2e Compound 2d (60 mg, 0.12 mmol) was dissolved in dichloromethane (3 mL), and 4 M hydrogen chloride in 1,4-dioxane solution (0.9 mL) was slowly added under ice bath, and the mixture was reacted for 2 hours. The reaction solution was concentrated under reduced pressure and dried under vacuum to obtain the crude product, title compound 2e (61 mg, yield: 100%), which was used in the next reaction without purification. MS m / z (ESI): 401.4 [M+1].

[0411] Step 5 5-(4-(1-(4-((S)-2-(3-chloro-4-cyanophenyl)-3-methyl-2,8-diazaspiro[4.5]dec-8-yl)benzoyl)piperidin-4-yl)piperazin-1-yl)-N-(2,6-dioxopiperidin-3-yl)pyridinecarboxamide 2 (diastereomeric mixture) N,N-Dimethylformamide (2 mL), compound 2e (52 mg, 0.10 mmol), and compound 1h (50 mg, 0.078 mmol) were added to a 25 mL three-neck flask in this order, and N,N-diisopropylethylamine (102 mg, 0.79 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (60 mg, 0.16 mmol) were slowly added in an ice bath. The system was then warmed to room temperature and reacted for 16 hours. The reaction solution was filtered and separated and purified by high-performance liquid preparative chromatography (Waters 2545, elution system: 10 mmol / L aqueous ammonium bicarbonate solution and acetonitrile, acetonitrile gradient: 36% to 51%, flow rate: 30 mL / min) to obtain the title compound 2 (diastereomeric mixture, ratio 1:1, 32 mg, yield: 51%). MS m / z (ESI): 792.3 [M+1]. 1 H NMR (500 MHz, DMSO-d 6 ): δ 10.84 (s, 1H), 8.72 (d, 1H), 8.31 (s, 1H), 7.86 (d, 1H), 7.59 (d, 1H), 7.41 (d, 1H), 7.26 (d, 2H), 6.95 (d, 2H), 6.80 (s, 1H), 6.66 (d, 1H), 4.84-4.61 (m, 1H), 4.40-3.88 (m, 3H), 3.60-3.32 (m, 7H), 3.28-3.06 (m, 2H), 3.02-2.72 (m, 3H), 2.71-2.57 (m, 6H), 2.33-2.09 (m, 2H), 2.07-1.94 (m, 1H), 1.91-1.65 (m, 4H), 1.62-1.31 (m, 5H), 1.30-0.98 (m, 4H).

[0412] Example 3 4-(4-((1-(4-((S)-2-(3-chloro-4-cyanophenyl)-3-methyl-2,8-diazaspiro[4.5]dec-8-yl)benzoyl)piperidin-4-yl)methyl)piperazin-1-yl)-N-(2,6-dioxopiperidin-3-yl)-2-fluorobenzamide 3 (diastereomeric mixture) [ka] [ka]

[0413] Step 1 (±)-tert-butyl 4-((4-(4-((2,6-dioxopiperidin-3-yl)aminocarbonyl)-3-fluorophenyl)piperazin-1-yl)methyl)piperidine-1-carboxylate 3b Dichloromethane (4 mL), methanol (1 mL), and compound 1d (80 mg, 0.22 mmol) were added to a 25 mL three-neck flask in that order, and anhydrous sodium acetate (54 mg, 0.66 mmol) was added and stirred for 15 minutes. 4-formylpiperidine-1-carboxylate tert-butyl 3a (65 mg, 0.30 mmol, BiDe Pharmaceutical) was added and stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (92 mg, 0.43 mmol) was slowly added and the mixture was allowed to react for 16 hours. While cooling with an ice bath, 10 mL of saturated sodium bicarbonate solution was added into the system to quench the reaction, and the mixture was extracted with dichloromethane (20 mL×3), the organic phases were combined and washed with saturated sodium chloride solution (20 mL×3), the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography with eluent system A to obtain the title compound 3b (82 mg, yield: 71%). MS m / z (ESI): 530.2 [M-1].

[0414] Step 2 (±)-N-(2,6-dioxopiperidin-3-yl)-2-fluoro-4-(4-(piperidin-4-yl)methyl)piperazin-1-yl)benzamide dihydrochloride 3c Compound 3b (82 mg, 0.15 mmol) was dissolved in dichloromethane (3 mL), and 4 M hydrogen chloride in 1,4-dioxane solution (0.8 mL) was slowly added under ice bath, and the mixture was reacted for 3 hours. The reaction solution was concentrated under reduced pressure and dried under vacuum to obtain the crude product, title compound 3c (77 mg, yield: 100%), which was used in the next reaction without purification. MS m / z (ESI): 432.4 [M+1].

[0415] Step 3 4-(4-((1-(4-((S)-2-(3-chloro-4-cyanophenyl)-3-methyl-2,8-diazaspiro[4.5]dec-8-yl)benzoyl)piperidin-4-yl)methyl)piperazin-1-yl)-N-(2,6-dioxopiperidin-3-yl)-2-fluorobenzamide 3 (diastereomeric mixture) N,N-dimethylformamide (2 mL), compound 3c (51 mg, 0.10 mmol), and compound 1h (50 mg, 0.078 mmol) were added in this order to a 25 mL three-neck flask. N,N-diisopropylethylamine (152 mg, 1.18 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (60 mg, 0.16 mmol) were slowly added in an ice bath, and the system was then warmed to room temperature and reacted for 16 hours. The reaction solution was filtered and separated and purified by high-performance liquid preparative chromatography (Waters 2545, elution system: 10 mmol / L aqueous ammonium bicarbonate solution and acetonitrile, acetonitrile gradient: 36% to 51%, flow rate: 30 mL / min) to obtain the title compound 3 (diastereomeric mixture, ratio 1:1, 48 mg, yield: 74%). MS m / z (ESI): 823.6 [M+1]. 1 H NMR (500 MHz, DMSO-d 6): δ 10.85 (s, 1H), 8.05 (t, 1H), 7.72-7.52 (m, 2H), 7.25 (d, 2H), 6.95 (d, 2H), 6.88-6.72 (m, 3H), 6.66 (d, 1H), 4.80-4.64 (m, 1H), 4.34-3.82 (m, 3H), 3.44 (d, 1H), 3.32-3.05 (m, 7H), 3.03-2.66 (m, 4H), 2.48-2.35 (m, 4H), 2.32-2.07 (m, 4H), 2.05-1.94 (m, 1H), 1.92-1.66 (m, 5H), 1.62-1.37 (m, 4H), 1.35-1.17 (m, 4H), 1.14-0.95 (m, 2H).

[0416] Example 4 5-(4-((1-(4-((S)-2-(3-chloro-4-cyanophenyl)-3-methyl-2,8-diazaspiro[4.5]dec-8-yl)benzoyl)piperidin-4-yl)methyl)piperazin-1-yl)-N-(2,6-dioxopiperidin-3-yl)pyridinecarboxamide 4 (diastereomeric mixture) [ka] [ka]

[0417] Step 1 (±)-tert-Butyl 4-((4-(6-((2,6-dioxopiperidin-3-yl)aminocarbonyl)pyridin-3-yl)piperazin-1-yl)methyl)piperidine-1-carboxylate 4a In a 25mL three-neck flask, dichloromethane (4mL), methanol (1mL), and compound 2c (100mg, 0.28mmol) were added in order, anhydrous sodium acetate (70mg, 0.85mmol) was added, and the mixture was stirred for 15 minutes. Compound 3a (80mg, 0.38mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (120mg, 0.57mmol) was slowly added, and the mixture was reacted for 16 hours. While cooling in an ice bath, 10mL of saturated sodium bicarbonate solution was added to the system to quench the reaction, and the mixture was extracted with dichloromethane (20mL x 3), and the organic phases were combined and washed with saturated sodium chloride solution (20mL x 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 silica gel column chromatography with eluent system A to obtain the title compound 4a (125mg, yield: 85%). MS m / z (ESI): 515.4 [M+1].

[0418] Step 2 (±)-N-(2,6-dioxopiperidin-3-yl)-5-(4-(piperidin-4-yl)methyl)piperazin-1-yl)pyridinecarboxamide trihydrochloride 4b Compound 4a (125 mg, 0.24 mmol) was dissolved in dichloromethane (3 mL), and 4 M hydrogen chloride in 1,4-dioxane solution (1.2 mL) was slowly added under ice bath, and the mixture was reacted for 4 hours. The reaction solution was concentrated under reduced pressure and dried under vacuum to obtain the crude product, title compound 4b (126 mg, yield: 100%), which was used in the next reaction without purification. MS m / z (ESI): 415.5 [M+1].

[0419] Step 3 5-(4-((1-(4-((S)-2-(3-chloro-4-cyanophenyl)-3-methyl-2,8-diazaspiro[4.5]dec-8-yl)benzoyl)piperidin-4-yl)methyl)piperazin-1-yl)-N-(2,6-dioxopiperidin-3-yl)pyridinecarboxamide 4 (diastereomeric mixture) N,N-Dimethylformamide (2 mL), compound 4b (51 mg, 0.10 mmol), and compound 1h (50 mg, 0.078 mmol) were added in this order to a 25 mL three-neck flask, and N,N-diisopropylethylamine (152 mg, 1.18 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (60 mg, 0.16 mmol) were slowly added in an ice bath. The system was then warmed to room temperature and reacted for 16 hours. The reaction solution was filtered and separated and purified by high-performance liquid preparative chromatography (Waters 2545, elution system: 10 mmol / L aqueous ammonium bicarbonate solution and acetonitrile, acetonitrile gradient: 36% to 51%, flow rate: 30 mL / min) to obtain the title compound 4 (diastereomeric mixture, ratio 1:1, 35 mg, yield: 55%). MS m / z (ESI): 806.2 [M+1]. 1 H NMR (500 MHz, DMSO-d 6 ): δ 10.85 (s, 1H), 8.73 (d, 1H), 8.32 (s, 1H), 7.87 (d, 1H), 7.60 (d, 1H), 7.42 (d, 1H), 7.25 (d, 2H), 6.95 (d, 2H), 6.80 (s, 1H), 6.66 (d, 1H), 4.86-4.63 (m, 1H), 4.28-3.82 (m, 3H), 3.44 (d, 1H), 3.41-3.32 (m, 7H), 3.26-3.10 (m, 2H), 2.98-2.72 (m, 3H), 2.64-2.53 (m, 4H), 2.32-2.14 (m, 4H), 2.07-1.94 (m, 1H), 1.92-1.66 (m, 5H), 1.62-1.56 (m, 1H), 1.52-1.40 (m, 2H), 1.33-1.17 (m, 4H), 1.14-0.98 (m, 2H).

[0420] Example 5 4-(3-(4-((5-((S)-2-(3-chloro-4-cyanophenyl)-3-methyl-2,8-diazaspiro[4.5]decane-8-carbonyl)pyridin-2-yl)thio)piperidin-1-yl)azetidin-1-yl)-N-(2,6-dioxopiperidin-3-yl)-2-fluorobenzamide 5 (diastereomeric mixture) [ka] [ka]

[0421] Step 1 (S)-2-Chloro-4-(8-(6-fluoronicotinoyl)-3-methyl-2,8-diazaspiro[4.5]dec-2-yl)benzonitrile 5c 6-Fluoronicotinic acid 5b (139 mg, 0.98 mmol, Bi De Pharmaceutical) was weighed and placed in a 50 mL eggplant-shaped flask, N,N-dimethylformamide (3 mL) was added, followed by N,N-diisopropylethylamine (446 mg, 3.45 mmol, 0.86 mL), O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (563 mg, 1.48 mmol), and stirred for 15 minutes. Then, compound (S)-2-chloro-4-(3-methyl-2,8-diazaspiro[4.5]dec-2-yl)benzonitrile 5a (284 mg, 0.98 mmol, prepared according to the method disclosed in the patent application "WO2021055756A1, Example 10 on page 211 of the specification") was added, and the mixture was allowed to react for 2 hours. Water (5 mL) was added to the system, extracted with ethyl acetate (10 mL×3), the organic phases were combined, washed with saturated sodium chloride solution (10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography with eluent system B to give the title compound 5c (407 mg, yield: 100%). MS m / z (ESI): 413.2 [M+1].

[0422] Step 2 (S)-tert-Butyl 4-((5-(2-(3-chloro-4-cyanophenyl)-3-methyl-2,8-diazaspiro[4.5]decane-8-carbonyl)pyridin-2-yl)thio)piperidine-1-carboxylate 5e Compound 5c (407 mg, 0.98 mmol) and tert-butyl 4-mercaptopiperidine-1-carboxylate 5d (428 mg, 1.96 mmol) were weighed and placed in a 50 mL eggplant-shaped flask, and N,N-dimethylformamide (5 mL) and cesium carbonate (481 mg, 1.48 mmol) were added, followed by reaction at 110° C. for 5 hours. Heating was stopped, water (8 mL) was added to the system, and extraction was performed with ethyl acetate (15 mL×3). The organic phases were combined, washed with saturated sodium chloride solution (20 mL) in turn, and dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the obtained residue was purified by silica gel column chromatography using eluent system B to obtain the title compound 5e (596 mg, yield: 99%). MS m / z (ESI): 510.1 [M-99].

[0423] Step 3 (S)-2-Chloro-4-(3-methyl-8-(6-(piperidin-4-ylthio)nicotinoyl)-2,8-diazaspiro[4.5]dec-2-yl)benzonitrile hydrochloride 5f Compound 5e (596 mg, 0.98 mmol) was weighed and placed in a 25 mL eggplant-shaped flask, and a 4 M solution of hydrogen chloride in 1,4-dioxane (5 mL) was added and reacted for 2 hours. The system was then concentrated and dried to obtain the title compound 5f (528 mg, yield: 99%). The crude product was used in the next reaction without purification. MS m / z (ESI): 510.1 [M+1].

[0424] Step 4 Methyl 2-fluoro-4-(3-hydroxyazetidin-1-yl)benzoate 5i Methyl 2-fluoro-4-bromobenzoate 5g (3g, 12.9mmol, BiDe Pharmaceutical) and azetidin-3-ol hydrochloride 5h (1.41g, 12.87mmol, BiDe Pharmaceutical) were weighed and placed in a 100mL eggplant-shaped flask, and palladium acetate (289mg, 1.289mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (962mg, 1.55mmol), and cesium carbonate (12.6g, 38.67mmol) were added in that order, followed by the addition of 1,4-dioxane (30mL), and the mixture was allowed to react at 105°C for 5 hours. After the reaction solution was cooled to room temperature, the reaction solution was filtered through diatomaceous earth, the filter cake was washed with ethyl acetate (15 mL × 3), the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography with eluent system B to obtain the title compound 5i (1.8 g, yield: 62%). MS m / z (ESI): 226.1 [M+1].

[0425] Step 5 2-Fluoro-4-(3-hydroxyazetidin-1-yl)benzoic acid 5j Compound 5i (600 mg, 2.66 mmol) was weighed and placed in a 50 mL eggplant-shaped flask, tetrahydrofuran (10 mL) was added to dissolve it, and an aqueous solution (2 mL) of sodium hydroxide (533 mg, 13.32 mmol) was added thereto and reacted at 80° C. for 4 hours. After the reaction solution was cooled to room temperature, 1 M hydrochloric acid was added to the system to adjust the pH to 3-4, the reaction solution was concentrated under reduced pressure to remove the organic solvent, filtered, and the filter cake was collected to obtain the title compound 5j (560 mg, 99%). MS m / z (ESI): 212.3 [M+1].

[0426] Step 6 (±)-N-(2,6-dioxopiperidin-3-yl)-2-fluoro-4-(3-hydroxyazetidin-1-yl)benzamide 5k Compound 5j (653 mg, 3.09 mmol) was weighed and placed in a 50 mL eggplant flask, N,N-dimethylformamide (5 mL) was added, followed by N,N-diisopropylethylamine (1.2 g, 9.28 mmol, 1.61 mL), O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (1.76 g, 4.63 mmol), and after stirring for 15 minutes, compound 1b (763 mg, 4.63 mmol) was added. The reaction was allowed to proceed for 2 hours, water (8 mL) was added to the system, and the mixture was extracted with ethyl acetate (15 mL x 3). The organic phases were combined, washed with saturated sodium chloride solution (20 mL), and dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the resulting residue was purified by silica gel column chromatography with eluent system A to give the title compound 5k (260 mg, 26%). MS m / z (ESI): 322.3 [M+1].

[0427] Step 7 (±)-N-(2,6-dioxopiperidin-3-yl)-2-fluoro-4-(3-oxoazetidin-1-yl)benzamide 5l Compound 5k (50 mg, 0.16 mmol) was weighed and placed in a 50 mL eggplant flask, and dichloromethane (10 mL) and sodium bicarbonate (26 mg, 0.31 mmol) were added. Under ice-water bath conditions, Dess-Martin oxidant (73 mg, 0.172 mmol) was added, and the system was allowed to warm to room temperature naturally and react for 12 hours. Saturated sodium thiosulfate solution (5 mL) and water (5 mL) were added to the system, and the system was extracted with dichloromethane (10 mL x 3). The organic phases were combined, washed with saturated sodium chloride solution (15 mL) in turn, and dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the obtained residue was purified by silica gel column chromatography using eluent system A to obtain the title compound 5l (35 mg, 70%). MS m / z (ESI): 320.1 [M+1].

[0428] Step 8 4-(3-(4-((5-((S)-2-(3-chloro-4-cyanophenyl)-3-methyl-2,8-diazaspiro[4.5]decane-8-carbonyl)pyridin-2-yl)thio)piperidin-1-yl)azetidin-1-yl)-N-(2,6-dioxopiperidin-3-yl)-2-fluorobenzamide 5 (diastereomeric mixture) Compound 5f (18 mg, 0.033 mmol) was weighed and placed in a 25 mL eggplant-shaped flask, and methanol (2 mL) and sodium acetate (13.8 mg, 0.16 mmol) were added, followed by reaction at 50 ° C for 30 minutes. Compound 5l (32 mg, 0.099 mmol) and acetic acid (4 mg, 0.066 mmol) were added to the system, and the reaction was continued for 1 hour, followed by sodium cyanoborohydride (12 mg, 0.02 mmol) and reaction for 12 hours. The reaction solution was filtered, and separated and purified by high-performance liquid preparative chromatography (Waters-2545, elution system: 10 mmol / L aqueous solution of ammonium bicarbonate and acetonitrile, acetonitrile gradient: 45% to 60%, flow rate: 30 mL / min), to obtain the title compound 5 (diastereomeric mixture, ratio 1:1, 10 mg, yield: 37%). MS m / z (ESI): 813.2 [M+1]. 1 H NMR (500 MHz, DMSO-d 6 ): δ 10.83 (s, 1H), 8.45 (s, 1H), 7.98 (t, 1H), 7.78-7.50 (m, 3H), 7.33 (d, 1H), 6.77 (s, 1H), 6.64 (d, 1H), 6.28 (d, 1H), 6.23 (d, 1H), 4.80-4.66 (m, 1H), 4.14-3.95 (m, 3H), 3.93-3.64 (m, 4H), 3.57-3.38 (m, 3H), 2.93-2.60 (m, 4H), 2.32-1.95 (m, 8H), 1.84-1.35 (m, 9H), 1.19 (d, 3H).

[0429] Example 6 (S)-2-Chloro-4-(8-(4-(4-(4-(4-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)phenyl)piperazin-1-yl)-[1,4'-bipiperidine]-1'-carbonyl)phenyl)-3-methyl-2,8-diazaspiro[4.5]dec-2-yl)benzonitrile 6 [ka] [ka]

[0430] Step 1 tert-Butyl 4-(4-(4-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)phenyl)piperazin-1-yl)piperidine-1-carboxylate 6b 6 mL of a mixed solvent of 1,2-dichloroethane and methanol (V / V=5 / 1) was added to a 50 mL reaction flask, and 1-(4-(piperazin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione hydrochloride 6a (500 mg, 1.61 mmol, Scheme 1 on page 345 of the specification in patent application WO2020132561 A1) was added. 15" (prepared by the method disclosed in), anhydrous sodium acetate (660 mg, 8.05 mmol) was added and stirred at room temperature for 10 minutes, compound 1e (960 mg, 4.82 mmol) was added and the reaction was stirred for 1 hour, sodium triacetoxyborohydride (685 mg, 3.23 mmol) was added and reacted for 3 hours, sodium cyanoborohydride (200 mg, 3.34 mmol) was added and reacted for 3 hours, compound 1e (960 mg, 4.82 mmol) was added and the reaction was continued for 12 hours, the reaction was quenched by adding saturated sodium bicarbonate solution (20 mL), extracted with 1,2-dichloroethane (50 mL x 3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography with eluent system A to obtain the title compound 6b (736 mg, yield: 99%). MS m / z (ESI): 458.6 [M+1].

[0431] Step 2 1-(4-(4-(piperidin-4-yl)piperazin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione dihydrochloride 6c Compound 6b (736 mg, 1.61 mmol) was dissolved in 5 mL of dichloromethane, and 4 M hydrogen chloride in 1,4-dioxane (5 mL) was slowly added under ice bath, and the mixture was allowed to react for 1 hour. The reaction solution was concentrated under reduced pressure and dried under vacuum to obtain the crude product, title compound 6c (692 mg, yield: 99%), which was used in the next reaction without purification. MS m / z (ESI): 358.3 [M+1].

[0432] Step 3 tert-Butyl 4-(4-(4-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)phenyl)piperazin-1-yl)-[1,4'-bipiperidine]-1'-carboxylate 6d A 50 mL reaction flask was charged with 10 mL of a mixed solution of 1,2-dichloromethane and methanol (V / V=7 / 3), compound 6c (300 mg, 0.70 mmol), and anhydrous sodium acetate (350 mg, 4.27 mmol), and stirred for 30 minutes. Compound 1e (400 mg, 2.01 mmol) was added, and stirring was continued for 10 minutes. Sodium cyanoborohydride (84 mg, 1.40 mmol) was added, and the mixture was reacted for 1 hour, and compound 1e (400 mg, 2.01 mmol) was added, and the mixture was heated to 50° C. and reacted overnight with stirring. The mixture was concentrated under reduced pressure and separated and purified by high-performance liquid preparative chromatography (Gilson GX-281, elution system: 10 mmol / L aqueous ammonium bicarbonate solution and acetonitrile, acetonitrile gradient: 28% to 48%, flow rate: 30 mL / min) to obtain the title compound 6d (138 mg, yield: 37%). MS m / z (ESI): 541.4 [M+1].

[0433] Step 4 1-(4-(4-([1,4'-bipiperidine]-4-yl)piperazin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione trihydrochloride 6e Compound 6d (36 mg, 0.066 mmol) was dissolved in 1 mL of dichloromethane, and 4 M hydrogen chloride in 1,4-dioxane solution (1 mL) was slowly added under ice bath, and the mixture was allowed to react for 1 hour. The reaction solution was concentrated under reduced pressure and dried under vacuum to obtain the crude product, title compound 6e (36 mg, yield: 99%), which was used in the next reaction without purification. MS m / z (ESI): 441.4 [M+1].

[0434] Step 5 (S)-2-Chloro-4-(8-(4-(4-(4-(4-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)phenyl)piperazin-1-yl)-[1,4'-bipiperidine]-1'-carbonyl)phenyl)-3-methyl-2,8-diazaspiro[4.5]dec-2-yl)benzonitrile 6 2mL of N,N-dimethylformamide, compound 1h (35mg, 0.085mmol), and compound 6e (42mg, 0.076mmol) were added to a 25mL reaction flask in that order, and then O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (36mg, 0.095mmol) and N,N-diisopropylethylamine (60mg, 0.464mmol) were added, and the mixture was reacted for 1 hour. The reaction solution was filtered and separated and purified by high-performance liquid preparative chromatography (Waters 2767-SQ Detecor2, elution system: 10mmol / L aqueous solution of ammonium bicarbonate and acetonitrile, acetonitrile gradient: 70% to 90%, flow rate: 30mL / min), to obtain the title compound 6 (4mg, yield: 6%). MS m / z (ESI): 832.4 [M+1]. 1 H NMR (500 MHz, DMSO-d 6): δ 10.26 (s, 1H), 7.60 (d, 1H), 7.27 (d, 2H), 7.15 (d, 2H), 7.01-6.85 (m, 4H), 6.80 (d, 1H), 6.66 (dd, 1H), 4.08-3.96 (m, 1H), 3.69 (t, 2H), 3.58-3.35 (m, 6H), 3.28-3.04 (m, 7H), 3.01-2.55 (m, 12H), 2.28-2.18 (m, 1H), 2.10-1.91 (m, 3H), 1.83-1.36 (m, 9H), 1.32-1.12 (m, 5H).

[0435] Example 7 (S)-2-Chloro-4-(8-(4-(4-(3-(4-(4-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)phenyl)piperazin-1-yl)azetidin-1-yl)piperidine-1-carbonyl)phenyl)-3-methyl-2,8-diazaspiro[4.5]dec-2-yl)benzonitrile 7 [ka] [ka]

[0436] Step 1 tert-Butyl 3-(4-(4-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)phenyl)piperazin-1-yl)azetidine-1-carboxylate 7b Compound 6a (500 mg, 1.82 mmol) and tert-butyl 3-oxoazetidine-1-carboxylate 7a (343 mg, 2.0 mmol, Bi De Pharmaceutical) were dissolved in 45 mL of a mixed solvent of dichloromethane and methanol (V / V=2 / 1), and anhydrous sodium acetate (897 mg, 10.94 mmol) was added, acetic acid (0.1 mL) was added, and the mixture was heated to 60° C. for 0.5 hours, and sodium triacetoxyborohydride (848 mg, 4.0 mmol) was added, and the mixture was heated to 60° C. for 12 hours. After filtration and concentration under reduced pressure, the resulting residue was purified by silica gel column chromatography using eluent system A to obtain the title compound 7b (440 mg, yield: 56%). MS m / z (ESI): 430.3 [M+1].

[0437] Step 2 1-(4-(4-(azetidin-3-yl)piperazin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione bistrifluoroacetate 7c Compound 7b (440 mg, 1.02 mmol) was dissolved in 15 mL of dichloromethane, trifluoroacetic acid (3 mL) was added dropwise, and the mixture was reacted for 2 hours, concentrated under reduced pressure, and dried under vacuum to obtain the title compound 7c (570 mg, yield: 100%). The crude product was used in the next reaction without purification.

[0438] Step 3 tert-Butyl 4-(3-(4-(4-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)phenyl)piperazin-1-yl)azetidin-1-yl)piperidine-1-carboxylate 7d In a 50mL reaction flask, 6.5mL of a mixed solution of 1,2-dichloroethane and methanol (V / V=10 / 3), compound 7c (100mg, 0.18mmol), and anhydrous sodium acetate (150mg, 1.83mmol) were added in that order, stirred for 30 minutes, compound 1e (400mg, 2.01mmol) was added, the temperature was raised to 50°C, reacted for 15 minutes, sodium cyanoborohydride (40mg, 0.67mmol) was added, and reacted for 12 hours. The mixture was concentrated under reduced pressure to remove the solvent, and the resulting residue was purified by silica gel column chromatography using eluent system A to obtain the title compound 7d (50mg, yield: 54%). MS m / z (ESI): 513.6 [M+1].

[0439] Step 4 1-(4-(4-(1-(piperidin-4-yl)azetidin-3-yl)piperazin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione trihydrochloride 7e Compound 7d (50 mg, 0.098 mmol) was dissolved in 1 mL of dichloromethane, and 4 M hydrogen chloride in 1,4-dioxane solution (2 mL) was slowly added under ice bath and reacted for 1 hour. The reaction solution was concentrated and dried under vacuum to obtain the crude product, title compound 7e (50 mg, yield: 98%), which was used in the next reaction without purification. MS m / z (ESI): 413.3 [M+1].

[0440] Step 5 (S)-2-Chloro-4-(8-(4-(4-(3-(4-(4-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)phenyl)piperazin-1-yl)azetidin-1-yl)piperidine-1-carbonyl)phenyl)-3-methyl-2,8-diazaspiro[4.5]dec-2-yl)benzonitrile 7 2mL of N,N-dimethylformamide, compound 1h (50mg, 0.12mmol), and compound 7e (50mg, 0.096mmol) were added to a 25mL reaction flask in this order, and O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (50mg, 0.13mmol) and N,N-diisopropylethylamine (100mg, 0.77mmol) were added, and the mixture was reacted at room temperature for 1 hour. The reaction solution was filtered and separated and purified by high-performance liquid preparative chromatography (Waters 2767-SQ Detecor2, elution system: 10mmol / L aqueous solution of ammonium bicarbonate and acetonitrile, acetonitrile gradient: 70% to 90%, flow rate: 30mL / min), to obtain the title compound 7 (10mg, yield: 13%). MS m / z (ESI): 804.4 [M+1]. 1 H NMR (500 MHz, DMSO-d 6 ): δ 10.26 (s, 1H), 7.59 (d, 1H), 7.23 (d, 2H), 7.14 (d, 2H), 7.01-6.85 (m, 4H), 6.80 (d, 1H), 6.65 (dd, 1H), 4.17-3.96 (m, 1H), 3.94-3.60 (m, 4H), 3.55-3.35 (m, 5H), 3.28-2.98 (m, 8H), 2.94-2.74 (m, 3H), 2.72-2.60 (m, 2H), 2.47-2.31 (m, 4H), 2.30-2.12 (m, 2H), 1.88-1.39 (m, 7H), 1.36-0.98 (m, 6H).

[0441] Example 8 (S)-2-Chloro-4-(8-(4-(4-((3-(4-(4-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)phenyl)piperazin-1-yl)azetidin-1-yl)methyl)piperidine-1-carbonyl)phenyl)-3-methyl-2,8-diazaspiro[4.5]dec-2-yl)benzonitrile 8 [ka] [ka]

[0442] Step 1 Compound 7c (44 mg, 0.079 mmol) was weighed and placed in a 25 mL eggplant-shaped flask, and 8 mL of a mixed solvent of dichloromethane and methanol (V / V=3 / 1) and anhydrous sodium acetate (81 mg, 0.99 mmol) were added and reacted for 15 minutes. (S)-2-chloro-4-(8-(4-(4-formylpiperidine-1-carbonyl)phenyl)-3-methyl-2,8-diazaspiro[4.5]dec-2-yl)benzonitrile 8a (50 mg, 0.099 mmol, prepared by the method disclosed in the patent application "Example 47 on page 265 of the specification in WO2021055756 A1") and acetic acid (4 mg, 0.066 mmol) were added to the system and reacted for 1 hour. Sodium cyanoborohydride (12 mg, 0.19 mmol) was added and reacted for 12 hours. The reaction solution was filtered and separated and purified by high-performance liquid preparative chromatography (Waters-2545, elution system: 10 mmol / L aqueous ammonium bicarbonate solution and acetonitrile, acetonitrile gradient: 45% to 60%, flow rate: 30 mL / min) to obtain the title compound 8 (20 mg, yield: 31%). MS m / z (ESI): 818.7 [M+1]. 1 H NMR (500 MHz, DMSO-d 6): δ 10.26 (s, 1H), 7.60 (d, 1H), 7.23 (d, 2H), 7.15 (d, 2H), 7.01-6.85 (m, 4H), 6.81 (d, 1H), 6.66 (dd, 1H), 4.07-3.98 (m, 1H), 3.70 (t, 2H), 3.56-3.35 (m, 6H), 3.28-2.98 (m, 7H), 2.94-2.74 (m, 3H), 2.72-2.64 (m, 2H), 2.62-2.52 (m, 4H), 2.42-2.20 (m, 6H), 1.88-1.40 (m, 8H), 1.21 (d, 3H), 1.13-0.96 (m, 2H).

[0443] Example 9 (S)-2-Chloro-4-(8-(4-(4-((4-(4-(4-(4-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)phenyl)piperazin-1-yl)piperidin-1-yl)methyl)piperidine-1-carbonyl)phenyl)-3-methyl-2,8-diazaspiro[4.5]dec-2-yl)benzonitrile 9 [ka]

[0444] Step 1 Compound 6c (44 mg, 0.10 mmol) was weighed and placed in a 25 mL eggplant-shaped flask, 8 mL of a mixed solvent of dichloromethane and methanol (V / V=3 / 1), anhydrous sodium acetate (92 mg, 1.12 mmol) was added, and the mixture was reacted for 15 minutes. Compound 8a (53 mg, 0.10 mmol), acetic acid (4 mg, 0.066 mmol) were added, and the mixture was reacted for 1 hour. Sodium triacetoxyborohydride (47 mg, 0.22 mmol) was added, and the mixture was reacted for 2 hours. The reaction solution was filtered, and the mixture was separated and purified by high-performance liquid preparative chromatography (Waters-2545, elution system: 10 mmol / L aqueous solution of ammonium hydrogen carbonate and acetonitrile, acetonitrile gradient: 45% to 60%, flow rate: 30 mL / min), to obtain the title compound 9 (20 mg, yield: 23%). MS m / z (ESI): 846.5 [M+1]. 1 H NMR (500 MHz, DMSO-d 6 ): δ 10.25 (s, 1H), 7.59 (d, 1H), 7.23 (d, 2H), 7.14 (d, 2H), 7.01-6.85 (m, 4H), 6.80 (d, 1H), 6.66 (dd, 1H), 4.06-3.98 (m, 1H), 3.69 (t, 2H), 3.51-3.38 (m, 2H), 3.26-2.99 (m, 7H), 2.94-2.74 (m, 4H), 2.71-2.66 (m, 2H), 2.71-2.66 (m, 4H), 2.64-2.57 (m, 5H), 1.92-1.62 (m, 10H), 1.61-1.36 (m, 6H), 1.20 (d, 3H), 1.08-0.96 (m, 2H).

[0445] Example 10 2-Chloro-4-((3S)-8-(4-(4-(4-(3-((2,6-dioxopiperidin-3-yl)amino)phenyl)piperazin-1-yl)piperidine-1-carbonyl)phenyl)-3-methyl-2,8-diazaspiro[4.5]dec-2-yl)benzonitrile 10 (diastereomeric mixture) [ka] [ka]

[0446] Step 1 (±)-tert-butyl 4-(4-(3-((2,6-dioxopiperidin-3-yl)amino)phenyl)piperazin-1-yl)piperidine-1-carboxylate 10b A 25mL three-neck flask was charged with 3mL of a mixed solution of dichloromethane and methanol (V / V=2 / 1), (±)-3-((3-(piperazin-1-yl)phenyl)amino)piperidine-2,6-dione hydrochloride 10a (90mg, 0.25mmol, prepared by the method disclosed in the patent application "Compound 86 on page 266 of the specification in WO 2018237026 A1") was added, anhydrous sodium acetate (103mg, 1.25mmol) was added, and the mixture was stirred for 15 minutes, and acetic acid (30mg, 0.49mmol) and compound 1e (148mg, 0.74mmol) were added, and the mixture was stirred at room temperature for 30 minutes, and sodium cyanoborohydride (38mg, 0.60mmol) was slowly added, and the mixture was allowed to react for 16 hours. While cooling with an ice bath, 10 mL of saturated sodium bicarbonate solution was added into the system to quench the reaction, and the mixture was extracted with dichloromethane (20 mL×3), the organic phases were combined and washed with saturated sodium chloride solution (20 mL×3), the organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography with eluent system A to obtain the title compound 10b (95 mg, yield: 80%). MS m / z (ESI): 472.8 [M+1].

[0447] Step 2 (±)-3-((3-(4-(piperidin-4-yl)piperazin-1-yl)phenyl)amino)piperidin...

Claims

1. A compound represented by general formula (I) or a pharmaceutically acceptable salt thereof, 【Chemistry 1】 During the ceremony, R is an aryl group or a heteroaryl group, wherein the aryl group and the heteroaryl group each independently optionally include a halogen, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a cyano group, —(CH ２ ) ｎ NR ａ R ｂ , nitro group, hydroxy group, hydroxyalkyl group, aminoalkyl group, alkoxyalkyl group, cycloalkylalkyl group, heterocyclylalkyl group, cycloalkyl group, heterocyclyl group, aryl group, and heteroaryl group, A is, 【Chemistry 2】 Selected from 【Transformation 3】 is a single or double bond, Q １ , Q ２ , Q ３ , Q ４ and Q ５ one of which is a carbon atom, and the remaining four are the same or different and each independently a nitrogen atom or CR′; Each R' may be the same or different and independently represent a hydrogen atom, a halogen, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cyano group, a hydroxy group, a nitro group, or -(CH ２ ) ｎ NR ｃ R ｄ Selected from R １ is selected from a hydrogen atom, an alkyl group, a haloalkyl group, a hydroxyalkyl group, an aminoalkyl group, and an alkoxyalkyl group; R ２ is selected from a hydrogen atom, a halogen, an alkyl group, a haloalkyl group, a hydroxyalkyl group, an alkoxy group, a haloalkoxy group, a hydroxy group, a cyano group, an aminoalkyl group, and an alkoxyalkyl group; X １ is a spirocyclic group, wherein said spirocyclic group optionally comprises a halogen, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a cyano group, a nitro group, a hydroxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, -OR ３ , -C(O)R ３ , -C(O)OR ３ , -S(O) ｍ R ３ , -NR ４ R ５ , —C(O)NR ４ R ５ , -S(O) ｍ NR ４ R ５ , ═O and ═S; X ２ is -C(O)-, -S(O) ２ - and - (CR ２ａ R ２ｂ ) ｍ１ Selected from - X ３ is selected from a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group, wherein the cycloalkyl group, the heterocyclyl group, the aryl group, and the heteroaryl group each independently optionally include a halogen, an alkyl group, an alkoxy group, a haloalkyl group, a haloalkoxy group, a cyano group, -(CH ２ ) ｎ NR ｅ R ｆ , a nitro group, a hydroxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, and ═O, X ４ Ha-J １ -J ２ -J ３ -J ４ -J ５ -, where J １ is X ３ is connected to J １ is -O-, -S-, -NR ６ -, -C(O)-, -S(O) ２ -, - (CR ７ R ８ ) ｍ２ -, an alkenyl group, and an alkynyl group; J ２ is a cycloalkyl group or a heterocyclyl group, wherein the cycloalkyl group and the heterocyclyl group are each independently optionally selected from halogen, alkyl group, alkoxy group, haloalkyl group, haloalkoxy group, cyano group, —(CH ２ ) ｎ NR ｇ R ｈ , a nitro group, a hydroxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, and ═O, J ３ is -O-, -S-, -NR ６ａ -, -C(O)-, -S(O) ２ -, - (CR ７ａ R ８ａ ) ｍ３ -, alkenyl, alkynyl, cycloalkyl and heterocyclyl groups, wherein the cycloalkyl and heterocyclyl groups are each independently optionally selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, cyano, -(CH ２ ) ｎ NR ｇ R ｈ , a nitro group, a hydroxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, and ═O, J ４ is selected from a bond, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group, wherein the cycloalkyl group, the heterocyclyl group, the aryl group, and the heteroaryl group are each independently optionally selected from halogen, alkyl group, alkoxy group, haloalkyl group, haloalkoxy group, cyano group, —(CH ２ ) ｎ NR ｇ R ｈ , a nitro group, a hydroxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, and ═O, J ５ is -C(O)NR ６ｂ -, -NR ６ｂ C(O)-, -O-, -S-, -NR ６ｂ -, -C(O)-, -S(O) ２ -, - (CR ７ｂ R ８ｂ ) ｍ４ -, alkenyl, alkynyl, cycloalkyl and heterocyclyl groups, wherein the cycloalkyl and heterocyclyl groups are each independently optionally selected from halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, cyano, -(CH ２ ) ｎ NR ｇ R ｈ , a nitro group, a hydroxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, a heteroaryl group, and ═O, R ａ , R ｂ , R ｃ , R ｄ , R ｅ , R ｆ , R ｇ , R ｈ , R ６ , R ６ａ and R ６ｂ are the same or different and are each independently selected from a hydrogen atom, an alkyl group, a haloalkyl group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, and a heterocyclylalkyl group; R ２ａ , R ２ｂ , R ７ , R ８ , R ７ａ , R ８ａ , R ７ｂ and R ８ｂ are the same or different and each independently selected from a hydrogen atom, a halogen, an alkyl group, an alkoxy group, a hydroxy group, an amino group, a cyano group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, and a heterocyclylalkyl group; R ３ are selected from a hydrogen atom, an alkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group, wherein said alkyl group, cycloalkyl group, heterocyclyl group, aryl group, and heteroaryl group are each independently optionally substituted with one or more substituents selected from a halogen, an alkyl group, an alkoxy group, a hydroxy group, an amino group, a cyano group, a nitro group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, ═O, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group; R ４ and R ５ are the same or different and each independently selected from a hydrogen atom, an alkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group, wherein the alkyl group, the cycloalkyl group, the heterocyclyl group, the aryl group, and the heteroaryl group are each independently optionally substituted with one or more substituents selected from a halogen, an alkyl group, an alkoxy group, a hydroxy group, an amino group, a cyano group, a nitro group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, ═O, an aminoalkyl group, an alkoxyalkyl group, a cycloalkylalkyl group, a heterocyclylalkyl group, a cycloalkyl group, a heterocyclyl group, an aryl group, and a heteroaryl group; Or, R ４ and R ５ together with the nitrogen atom to which it is linked form a heterocyclyl group, which is optionally substituted with one or more substituents selected from halogen, alkyl, alkoxy, hydroxy, amino, cyano, nitro, haloalkyl, haloalkoxy, hydroxyalkyl, ═O, aminoalkyl, alkoxyalkyl, cycloalkylalkyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl; n is 0, 1, 2 or 3; m is 0, 1 or 2; m1 is 0, 1, 2 or 3; m2 is 0, 1, 2 or 3; m3 is 0, 1, 2 or 3, and m4 is 0, 1, 2 or 3; The compound or a pharmaceutically acceptable salt thereof.

2. R is a phenyl group or a 5- or 6-membered heteroaryl group, wherein the phenyl group and the 5- or 6-membered heteroaryl group are each independently optionally selected from halogen, C １－６ Alkyl group, C １－６ Alkoxy group, C １－６ Haloalkyl group, C １－６ Haloalkoxy group, cyano group, amino group, nitro group, hydroxy group, and C １－６ hydroxyalkyl groups, and preferably R is 【Chemistry 4】 More preferably, R is selected from 【Transformation 5】 2. The compound of claim 1 having the general formula (I) or a medicament salt thereof, wherein:

3. X １ teeth 【Transformation 6】 and the bonds marked with * are X ２ is connected to R １ａ , R １ｂ , R １ｃ and R １ｄ are the same or different and each independently represent a hydrogen atom, a halogen, or C １－６ Alkyl group, C １－６ Alkoxy group, C １－６ Haloalkyl group, C １－６ Haloalkoxy group, cyano group, amino group, hydroxy group, and C １－６ hydroxyalkyl groups, Or, R １ａ and R １ｂ forms C═O together with the carbon atom to which it is attached, Or, R １ｃ and R １ｄ forms C═O together with the carbon atom to which it is attached, q is 0, 1, 2 or 3, r is 0, 1, 2 or 3, s is 0, 1, 2, 3 or 4, and t is 0, 1, 2, 3 or 4; 2. A compound of formula (I) according to claim 1 or a medicamentable salt thereof.

4. X ３ is a 6- to 10-membered aryl group or a 5- to 10-membered heteroaryl group, wherein the 6- to 10-membered aryl group and the 5- to 10-membered heteroaryl group are each independently optionally selected from halogen, C １－６ Alkyl group, C １－６ Alkoxy group, C １－６ Haloalkyl group, C １－６ Haloalkoxy group, cyano group, amino group, hydroxy group, and C １－６ hydroxyalkyl groups, and preferably X ３ is a phenyl group or a 6-membered heteroaryl group, wherein the phenyl group and the 6-membered heteroaryl group are each independently optionally substituted with one or more halogens.

5. J ２ is a 3- to 12-membered heterocyclyl group, wherein said 3- to 12-membered heterocyclyl group optionally contains halogen, C １－６ Alkyl group, C １－６ Alkoxy group, C １－６ Haloalkyl group, C １－６ is substituted with one or more substituents selected from a haloalkoxy group, a cyano group, an amino group, a hydroxy group, and ═O, and preferably ２ teeth 【Transformation 7】 where the bonds marked with * are selected from ３ 2. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, linked to:

6. J ３ is -O-, -S-, -NR ６ａ -, -C(O)-, -S(O) ２ -, - (CR ７ａ R ８ａ ) ｍ３ -, C ２－６ Alkenyl group, C ２－６ alkynyl groups, 3- to 8-membered cycloalkyl groups, and 3- to 8-membered heterocyclyl groups; R ６ａ is a hydrogen atom or C １－６ is an alkyl group, and R ７ａ and R ８ａ are the same or different and each independently represent a hydrogen atom, a halogen, a hydroxyl group, or C １－６ m3 is 0, 1, 2 or 3, and preferably J ３ is a bond or CH ２ 2. The compound of claim 1 having the general formula (I) or a medicament salt thereof, wherein:

7. J ４ is a 3- to 8-membered cycloalkyl group or a 3- to 8-membered heterocyclyl group, wherein said 3- to 8-membered cycloalkyl group and 3- to 8-membered heterocyclyl group are each independently optionally selected from halogen, C １－６ Alkyl group, C １－６ Alkoxy group, C １－６ Haloalkyl group, C １－６ is substituted with one or more substituents selected from a haloalkoxy group, a cyano group, an amino group, a hydroxy group, and ═O, and preferably ４ teeth 【Transformation 8】 Bonds marked with * are selected from ５ 2. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, linked to:

8. A compound represented by general formula (G) or a medicamentable salt thereof, 【Chemistry 9】 During the ceremony, R １ａ is a hydrogen atom, halogen, C １－６ Alkyl group, C １－６ Alkoxy group, C １－６ Haloalkyl group, C １－６ Haloalkoxy group, cyano group, amino group, hydroxy group, and C １－６ hydroxyalkyl groups, Z １ is N or CR ３ｂ and Z ２ is N or CR ３ｃ and R ３ａ , R ３ｂ and R ３ｃ are the same or different and each independently represent a hydrogen atom, a halogen, or C １－６ Alkyl group, C １－６ Alkoxy group, C １－６ Haloalkyl group, C １－６ Haloalkoxy group, cyano group, amino group, nitro group, hydroxy group, and C １－６ hydroxyalkyl groups, Ring B and ring C are the same or different and each independently represent a 3- to 12-membered cycloalkyl group or a 3- to 12-membered heterocyclyl group, and the 3- to 12-membered cycloalkyl group and the 3- to 12-membered heterocyclyl group each independently optionally contain halogen, C １－６ Alkyl group, C １－６ Alkoxy group, C １－６ Haloalkyl group, C １－６ substituted with one or more substituents selected from a haloalkoxy group, a cyano group, an amino group, a hydroxy group, and ═O; W １ is N or CR ３ｄ and W ２ is N or CR ３ｅ and W ３ is N or CR ３ｆ and W ４ is N or CR ３ｇ and R ３ｄ , R ３ｅ , R ３ｆ and R ３ｇ are the same or different and each independently represent a hydrogen atom, a halogen, or C １－６ Alkyl group, C １－６ Alkoxy group, C １－６ Haloalkyl group, C １－６ Haloalkoxy group, cyano group, amino group, hydroxy group, and C １－６ hydroxyalkyl groups, m3, X ２ , J １ , J ５ and A is as defined in claim 1; 2. A compound of formula (I) according to claim 1 or a medicamentable salt thereof.

9. A compound represented by general formula (III') or a medicamentable salt thereof, 【Chemistry 10】 During the ceremony, W １ is N or CR ３ｄ and W ２ is N or CR ３ｅ and W ３ is N or CR ３ｆ and W ４ is N or CR ３ｇ and R ３ｄ , R ３ｅ , R ３ｆ and R ３ｇ are the same or different and each independently represent a hydrogen atom, a halogen, or C １－６ Alkyl group, C １－６ Alkoxy group, C １－６ Haloalkyl group, C １－６ Haloalkoxy group, cyano group, amino group, hydroxy group, and C １－６ hydroxyalkyl groups, Z ３ , Z ４ , Z ５ and Z ６ are the same or different and each independently represent a N atom or CH; m3 is 0, 1, 2 or 3; x, x1, y, and y1 each independently represent 0, 1, or 2; J ５ is -C(O)NR ６ｂ -, -NR ６ｂ C(O)-, -O-, -S-, -NR ６ｂ -, -C(O)-, -S(O) ２ -, - (CR ７ｂ R ８ｂ ) ｍ４ -, C ２－６ Alkenyl group, C ２－６ alkynyl groups, 3- to 8-membered cycloalkyl groups, and 3- to 8-membered heterocyclyl groups; R ６ｂ is a hydrogen atom or C １－６ is an alkyl group, and R ７ｂ and R ８ｂ are the same or different and each independently represent a hydrogen atom, a halogen, a hydroxyl group, or C １－６ m4 is 0, 1, 2 or 3, and preferably J ５ is selected from a bond, a 3- to 8-membered heterocyclyl group, and a 3- to 8-membered cycloalkyl group; Z １ , Z ２ , R １ａ , R ３ａ , X ２ , J １ and A is as defined in claim 8; 2. A compound of formula (I) according to claim 1 or a medicamentable salt thereof.

10. A compound represented by general formula (III) or a medicamentable salt thereof, 【Chemistry 11】 During the ceremony, W １ is N or CR ３ｄ and W ２ is N or CR ３ｅ and W ３ is N or CR ３ｆ and W ４ is N or CR ３ｇ and R ３ｄ , R ３ｅ , R ３ｆ and R ３ｇ are the same or different and each independently represent a hydrogen atom, a halogen, or C １－６ Alkyl group, C １－６ Alkoxy group, C １－６ Haloalkyl group, C １－６ Haloalkoxy group, cyano group, amino group, hydroxy group, and C １－６ hydroxyalkyl groups, Z ３ , Z ４ , Z ５ and Z ６ are the same or different and each independently represent an N atom or CH, with the proviso that Z ３ and Z ４ at least one of is a N atom, m3 is 0, 1, 2 or 3; x, x1, y, and y1 are each independently 0, 1, or 2; Z １ , Z ２ , R １ａ , R ３ａ , X ２ , J １ and A is as defined in claim 8; 2. A compound of formula (I) according to claim 1 or a medicamentable salt thereof.

11. X ２ is -C(O)-, -S(O) ２ - and - (CR ２ａ R ２ｂ ) ｍ１ - is selected from R ２ａ and R ２ｂ are the same or different and each independently represent a hydrogen atom, a halogen, a hydroxyl group, or C １－６ alkyl group, m1 is 0, 1, 2 or 3, and preferably X ２ is a bond or —C(O)—, and more preferably, X ２ The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1, wherein is a bond.

12. J １ is -O-, -S-, -NR ６ -, -C(O)-, -S(O) ２ -, - (CR ７ R ８ ) ｍ２ -, C ２－６ Alkenyl group and C ２－６ alkynyl groups, R ６ is a hydrogen atom or C １－６ is an alkyl group, and R ７ and R ８ are the same or different and each independently represent a hydrogen atom, a halogen, a hydroxyl group, or C １－６ alkyl group, m2 is 0, 1, 2 or 3, and preferably J １ is —S— or —C(O)—, and more preferably, J １ The compound of formula (I) or a medicamentable salt thereof according to claim 1, wherein is -C(O)-.

13. A compound represented by general formula (IV'-1) or a medicinal salt thereof, 【Chemistry 12】 During the ceremony, R １ａ is a halogen, C １－６ Alkyl group, C １－６ Alkoxy group, C １－６ Haloalkyl group, C １－６ Haloalkoxy group, cyano group, amino group, hydroxy group, and C １－６ hydroxyalkyl groups, preferably R １ａ is C １－６ is an alkyl group, and more preferably, R １ａ is a methyl group, Q ２ is a carbon atom, and Q １ , Q ３ , Q ４ and Q ５ are the same or different and each independently represent a nitrogen atom or CR′, or Q ３ is a carbon atom, and Q １ , Q ２ , Q ４ and Q ５ are the same or different and each independently represent a nitrogen atom or CR′; R' may be the same or different and each independently represents a hydrogen atom, a halogen atom, C １－６ Alkyl group, C １－６ Alkoxy group, C １－６ Haloalkyl group, C １－６ Haloalkoxy group, C １－６ selected from a hydroxyalkyl group, a cyano group, a hydroxy group, and an amino group; Z １ , Z ２ , R ３ａ , W １ , W ２ , W ３ , W ４ , Z ４ , Z ５ , Z ６ , m3, x, x1, y and y1 are as defined in claim 9; 2. A compound of formula (I) according to claim 1 or a medicamentable salt thereof.

14. Z １ is CR ３ｂ and Z ２ is CR ３ｃ and R ３ａ , R ３ｂ and R ３ｃ are the same or different and each independently represent a hydrogen atom, a halogen, or C １－６ Alkyl group, C １－６ Alkoxy group, cyano group and C １－６ haloalkyl groups, preferably Z １ is CR ３ｂ and Z ２ is CR ３ｃ and R ３ａ is halogen or C １－６ is a haloalkyl group, and R ３ｂ is a hydrogen atom, and R ３ｃ is a hydrogen atom or C １－６ 9. The compound of formula (I) or a medicament salt thereof according to claim 8, wherein the compound is an alkyl group.

15. W １ is N or CR ３ｄ and W ２ is N or CR ３ｅ and W ３ is N or CR ３ｆ and W ４ is N or CR ３ｇ and R ３ｄ , R ３ｅ , R ３ｆ and R ３ｇ are the same or different and each independently represent a hydrogen atom or a halogen atom, preferably W １ is CR ３ｄ and W ２ is CR ３ｅ and W ３ is CR ３ｆ and W ４ is CR ３ｇ and R ３ｄ , R ３ｅ , R ３ｆ and R ３ｇ The compound of formula (I) or a medicament salt thereof according to claim 8, wherein are the same or different and each independently represent a hydrogen atom or a halogen. 【Request Item 16】 【Chemistry 13】 【Chemistry 14】 【Chemistry 15】 【Chemistry 16】 【Chemistry 17】 [Chemistry 18] 【Chemistry 19】 【Chemistry 20】 is selected from the compounds 2. A compound of formula (I) according to claim 1 or a medicamentable salt thereof.

17. A compound represented by general formula (MB) or a salt thereof, 【Chemistry 21】 During the ceremony, Q １ , Q ２ , Q ４ , Q ５ , Z ４ , Z ５ , Z ６ , x, x1, y, y1 and m3 are as defined in claim 13; A compound or a salt thereof. 【Request Item 18】 【Chemistry 22】 【Chemistry 23】 A compound selected from the compounds:

19. A method for preparing the compound of general formula (IV'-1) or a pharmaceutically acceptable salt thereof according to claim 13, comprising: 【Chemistry 24】 The method comprises subjecting a compound represented by general formula (IV-1A) or a salt thereof to a condensation reaction with a compound represented by general formula (IVB') or a salt thereof to obtain a compound represented by general formula (IV'-1) or a medicament-use salt thereof, where: R １ａ , Q １ , Q ２ , Q ３ , Q ４ , Q ５ , R ３ａ , W １ , W ２ , W ３ , W ４ , Z １ , Z ２ , Z ４ , Z ５ , Z ６ , x, x1, y, y1 and m3 are as defined in claim 13; method.

20. A pharmaceutical composition comprising a compound according to any one of claims 1 to 16 or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable vectors, diluents or excipients.

21. The pharmaceutical composition described in claim 20 for regulating the ubiquitination and degradation of androgen receptor (AR) protein.

22. A pharmaceutical composition according to claim 20 for treating and / or preventing an androgen receptor-mediated or dependent disease or condition, wherein the androgen receptor-mediated or dependent disease or condition is preferably selected from tumors, male sexual dysfunction and Kennedy's disease.

23. 23. The pharmaceutical composition of claim 22, wherein the androgen receptor-mediated or dependent disease or condition is selected from prostate cancer, benign prostatic hyperplasia, hirsutism, alopecia, anorexia nervosa, breast cancer, acne, male sexual dysfunction, Kennedy's disease and AIDS, preferably prostate cancer, more preferably hormone-sensitive prostate cancer or hormone-refractory prostate cancer.

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