Compounds containing a cyclobutyl group

Abstract

This relates to compounds containing a cyclobutyl group, belonging to the field of medicinal chemistry. Specifically, it concerns compounds of formula I, methods for producing them, pharmaceutical compositions containing said compounds, and their use in the treatment of diseases, such as cancer. [C1] TIFF2026529094000360.tif40156

Description

Technical Field

[0001] <Cross - reference to Related Applications> This application claims the priority and benefits of Chinese Patent Application No. 202311073391.5 filed with the China National Intellectual Property Administration on August 23, 2023, Chinese Patent Application No. 202410544791.8 filed with the China National Intellectual Property Administration on April 30, 2024, and Chinese Patent Application No. 202411125992.0 filed with the China National Intellectual Property Administration on August 15, 2024, and incorporates all of their contents herein by reference in their entirety.

[0002] <Technical Field> This application relates to compounds containing a cyclobutyl group, methods for their preparation, pharmaceutical compositions containing such compounds, and their use in the treatment of related diseases, such as cancer.

Background Art

[0003] The androgen receptor (AR) belongs to the steroid receptors of the nuclear receptor superfamily. When bound to androgens (such as testosterone, dihydrotestosterone), AR is released from the complex formed by heat shock proteins, forms a dimer through phosphorylation reactions, is transported into the nucleus, and binds to related DNA fragments, thereby stimulating the transcription of its target genes. The transcriptional activity of the androgen receptor activated by ligand binding is regulated by the proteins of co - activators. The main role of AR antagonists is to directly block the binding of testosterone or dihydrotestosterone to the androgen receptor, block the action of androgens on cells, play a role in androgen resistance and cell growth inhibition, ultimately cause apoptosis of cells, and play an important role in the treatment of prostate cancer.

[0004] PROTAC (proteolysis targeting chimera) molecules are a series of bifunctional compounds that can simultaneously bind to target proteins and E3 ubiquitin ligases. Such compounds can induce the recognition of target proteins by the cell's proteasome, cause the degradation of target proteins, and effectively reduce the content of target proteins in cells. By introducing ligands capable of binding to different target proteins into PROTAC molecules, it becomes possible to use the technology of PROTAC molecules in the treatment of various diseases. This technology has attracted extensive attention in recent years.

Summary of the Invention

Means for Solving the Problems

[0005] In one aspect, the present application relates to a compound of formula I, its stereoisomer or its pharmaceutically acceptable salt,

Chemical Formula

[0006] In some embodiments, ring A is absent, or C 5~10 Selected from a cycloalkenyl group, a 5-10 member heterocycloalkenyl group, a phenyl group, or a 5-6 member heteroaryl group.

[0007] In some embodiments, ring A is absent, or C 5~9 Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, a phenyl group, or a 5- to 6-membered heteroaryl group.

[0008] In some embodiments, ring A is absent, or C 5~7 Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, a phenyl group, or a 5- to 6-membered heteroaryl group.

[0009] In some embodiments, ring A is absent, or C 5~6 Selected from a cycloalkenyl group, a 5-10 member heterocycloalkenyl group, a phenyl group, or a 5-6 member heteroaryl group.

[0010] In some embodiments, ring A is absent, or C 5~6 Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, a phenyl group, or a 5- to 6-membered heteroaryl group.

[0011] In some embodiments, ring A is absent, or C 5~6 Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, a phenyl group, or a 5-membered heteroaryl group.

[0012] In some embodiments, ring A is absent, or C 5~6 Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, a phenyl group, a pyrrolyl group, a pyrazolyl group, a furyl group, or an oxazolyl group.

[0013] In some embodiments, ring A is absent or is selected from a C5 cycloalkenyl group, a C6 cycloalkenyl group, a 5-membered heterocycloalkenyl group, a 6-membered heterocycloalkenyl group, a 7-membered heterocycloalkenyl group, an 8-membered heterocycloalkenyl group, a 9-membered heterocycloalkenyl group, a phenyl group, a pyrrolyl group, a pyrazolyl group, a furyl group or an oxazolyl group.

[0014] In some embodiments, ring A is absent or is selected from a cyclopentenyl group, a monocyclohexenyl group, a bicyclohexenyl group, a dihydropyrrolyl group, a tetrahydropyridinyl group, a tetrahydroazepinyl group, an azaspirooctenyl group, an azaspirononenyl group, a phenyl group, a pyrrolyl group, a pyrazolyl group, a furyl group, an oxazolyl group or a dihydrooxazinyl group.

[0015] In some specific embodiments, ring A is selected from a C 5~10 cycloalkenyl group, a 5- to 10-membered heterocycloalkenyl group or a 5- to 6-membered heteroaryl group.

[0016] In some specific embodiments, ring A is a C 5~9 cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group or a 5- to 6-membered heteroaryl group.

[0017] In some specific embodiments, ring A is a C 5~7 cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group or a 5- to 6-membered heteroaryl group.

[0018] In some specific embodiments, ring A is a C 5~6 cycloalkenyl group, a 5- to 10-membered heterocycloalkenyl group or a 5- to 6-membered heteroaryl group.

[0019] In some specific embodiments, ring A is a C 5~6 cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group or a 5- to 6-membered heteroaryl group.

[0020] In some specific embodiments, ring A is C 5~6 Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, or a 5-membered heteroaryl group.

[0021] In some specific embodiments, ring A is C 5~10 Selected from a cycloalkenyl group or a 5-10 membered heterocycloalkenyl group. In some specific embodiments, ring A is C 5~9 Selected from a cycloalkenyl group or a 5- to 9-membered heterocycloalkenyl group. In some specific embodiments, ring A is C 5~8 Selected from cycloalkenyl groups. In some specific embodiments, ring A is C 5~6 The ring A is selected from cycloalkenyl groups. In some specific embodiments, ring A is selected from 5- to 9-membered heterocycloalkenyl groups. In some embodiments, ring A is selected from 5- to 9-membered heterocycloalkenyl groups containing 1-2 heteroatoms selected from N or O. In some embodiments, ring A is selected from 5- to 8-membered heterocycloalkenyl groups containing 1-2 heteroatoms selected from N or O. In some embodiments, ring A is selected from 5- to 7-membered heterocycloalkenyl groups containing 1-2 heteroatoms selected from N or O. In some embodiments, ring A is selected from 5- to 7-membered heterocycloalkenyl groups containing 1-2 N atoms.

[0022] In some specific embodiments, ring A is selected from a cyclopentenyl group, a monocyclohexenyl group, a bicyclohexenyl group, a dihydropyrrolyl group, a tetrahydropyridinyl group, a tetrahydroazepinyl group, an azaspirononenyl group, an azaspirooctenyl group, or a dihydrooxazinyl group.

[0023] In some embodiments, ring A is a cyclopentenyl group. In some embodiments, ring A is a monocyclohexenyl group. In some embodiments, ring A is a bicyclohexenyl group. In some embodiments, ring A is a dihydropyrrolyl group. In some embodiments, ring A is a tetrahydropyridinyl group. In some embodiments, ring A is a tetrahydroazepinyl group. In some embodiments, ring A is an azaspirononenyl group. In some embodiments, ring A is an azaspirooctenyl group. In some embodiments, ring A is a dihydrooxazinyl group.

[0024] In some more specific embodiments, ring A is selected from a phenyl group, a pyrrolyl group, a pyrazolyl group, a furyl group, or an oxazolyl group.

[0025] In some more specific embodiments, ring A is selected from a phenyl group, a pyrrolyl group, or a pyrazolyl group.

[0026] In some embodiments, ring B is selected from a phenyl group or a 6-membered heteroaryl group, for example, a 6-membered heteroaryl group containing 1 to 3 or 1 to 2 nitrogen atoms. In some embodiments, ring B is a phenyl group.

[0027] In some embodiments, ring C is selected from a five-membered heteroaryl group. In some embodiments, ring C is selected from an isoxazolyl group or a furyl group.

[0028] In some specific embodiments, ring C is an isoxazolyl group. In some specific embodiments, ring C is a furyl group.

[0029] In some specific embodiments, when ring A is present and both ring A and ring B are phenyl groups, ring C is not an oxazolyl group.

[0030] In some embodiments, R1 The substitution position is selected from ring A or ring B. In some embodiments, R 1 The substitution position is selected from ring A. In some embodiments, R 1 The substitution position is selected from ring B. In some embodiments, R 1 The substitution position is selected from ring C.

[0031] In some embodiments, ring F is connected to L. In some embodiments, ring A is connected to L. In some embodiments, ring B is connected to L. In some embodiments, ring C is connected to L. In some embodiments, ring A is connected to the following fragment. [ka] In some embodiments, ring B is connected to the following fragments. [ka] In some embodiments, ring C is linked to the following fragments. [ka] In some embodiments, rings F and A are connected to L, respectively, and ring C is connected to the following fragment. [ka]

[0032] In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] They are selected from among them. In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] They are selected from among them. In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] They are selected from among them. In some embodiments, the following structural fragment [ka] teeth, [ka] They are selected from among them. In some embodiments, the following structural fragment [ka] teeth, [ka] They are selected from among them. In some embodiments, the following structural fragment [ka] teeth, [ka] They are selected from among them.

[0033] In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] They are selected from among them. In some embodiments, the following structural fragment [ka] teeth, [ka] They won't be chosen. In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] They won't be chosen.

[0034] In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] They are selected from among them. In some embodiments, the following structural fragment [ka] teeth, [ka] They won't be chosen. In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] They won't be chosen.

[0035] In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] They are selected from among them.

[0036] In some embodiments, the following structural fragment [ka] teeth, [ka] That is the case. In some embodiments, the following structural fragment [ka] teeth, [ka] That is the case. In some embodiments, the following structural fragment [ka] teeth, [ka] That is the case. In some embodiments, the following structural fragment [ka] teeth, [ka] That is the case. In some embodiments, the following structural fragment [ka] teeth, [ka] That is the case. In some embodiments, the following structural fragment [ka] teeth, [ka] That is the case. In some embodiments, the following structural fragment [ka] teeth, [ka] That is the case. In some embodiments, the following structural fragment [ka] teeth, [ka] That is the case. In some embodiments, the following structural fragment [ka] teeth, [ka] That is the case. In some embodiments, the following structural fragment [ka] teeth, [ka] That is the case. In some embodiments, the following structural fragment [ka] teeth, [ka] That is the case. In some embodiments, the following structural fragment [ka] teeth, [ka] That is the case.

[0037] In some embodiments, each R 1 These are halogens, -OH, -NH2, -CN, and C 1~6 Alkyl alkyl group, C 1~6 Alkoxy group, or halo C1~6 A molecule independently selected from alkyl groups, and the aforementioned -OH, -NH2, C 1~6 Alkyl alkyl group, C 1~6 Alkoxy group, or halo C 1~6 The alkyl group is optionally substituted with one or more substituents. In some embodiments, each R 1 These are halogens, -OH, -NH2, -CN, and C 1~4 Alkyl alkyl group, C 1~4 Alkoxy group, or halo C 1~4 Selected independently of alkyl groups. In some embodiments, each R 1 These are halogens, -OH, -NH2, -CN, and C 1~3 Alkyl alkyl group, C 1~3 Alkoxy group, or halo C 1~3 Selected independently of alkyl groups. In some embodiments, each R 1 R is independently selected from fluorine, chlorine, bromine, -OH, -NH2, or -CN. In some embodiments, each R 1 R is independently selected from fluorine, chlorine, or bromine. In some embodiments, each R 1 It is fluorine independently.

[0038] In some embodiments, n is selected from 0, 1, or 2. In some embodiments, n is selected from 0 or 1. In some specific embodiments, n is 0.

[0039] In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] They are selected from among them.

[0040] In some embodiments, L is a C optionally substituted by one or more substituents 1~50 alkylene group, C 2~50 alkenylene group or C 2~50 alkynylene group, and one or more -CH2- in the C 1~50 alkylene group, C 2~50 alkenylene group or C 2~50 alkynylene group is optionally replaced by -O-, C 3~15 cycloalkyl group, 3- to 15-membered heterocycloalkyl group, 4- to 15-membered heterocycloalkenyl group, C 6~15 aryl group, 5- to 15-membered heteroaryl group, -NH-, -N(C 1~6 alkyl)- or -S-.

[0041] In some embodiments, L is a C optionally substituted by one or more substituents 1~30 alkylene group, C 2~30 alkenylene group or C 2~30 alkynylene group, and one or more -CH2- in the C 1~30 alkylene group, C 2~30 alkenylene group or C 2~30 alkynylene group is optionally replaced by -O-, C 3~12 cycloalkyl group, 3- to 12-membered heterocycloalkyl group, 4- to 12-membered heterocycloalkenyl group, C 6~12 aryl group, 5- to 12-membered heteroaryl group, -NH-, -N(C 1~6 alkyl)- or -S-.

[0042] In some embodiments, L is a C optionally substituted by one or more substituents 1~20 alkylene group, C 2~20 alkenylene group or C 2~20 alkynylene group, and one or more -CH2- in the C 1~20 alkylene group, C 2~20 alkenylene group or C 2~20 alkynylene group is optionally replaced by -O-, C 3~10Cycloalkyl groups, 3-11 member heterocycloalkyl groups, 4-10 member heterocycloalkenyl groups, C 6~10 Aryl group, 5-10 membered heteroaryl group, -NH-, -N(C) 1~6 It is replaced by alkyl)- or -S-.

[0043] In some embodiments, L is C, which is optionally substituted with one or more substituents. 1~15 Alkylene group, C 2~15 Alkenylene group or C 2~15 Selected from the alkynylene group, the C 1~15 Alkylene group, C 2~15 Alkenylene group or C 2~15 One or more -CH2- groups in the alkynylene group can be optionally -O-, C 3~9 Cycloalkyl groups, 3-11 member heterocycloalkyl groups, 4-8 member heterocycloalkenyl groups, C 6~8 Aryl group, 5-8 membered heteroaryl group, -NH-, -N(C) 1~4 It is replaced by alkyl)- or -S-.

[0044] In some embodiments, L is C, which is optionally substituted with one or more substituents. 1~10 Alkylene group, C 2~10 Alkenylene group or C 2~10 Selected from the alkynylene group, the C 1~10 Alkylene group, C 2~10 Alkenylene group or C 2~10 One or more -CH2- groups in the alkynylene group can be optionally -O-, C 3~9 Cycloalkyl groups, 3-11 member heterocycloalkyl groups, 4-6 member heterocycloalkenyl groups, C6 aryl groups, 5-6 member heteroaryl groups, -NH-, -N(C 1~3 It is replaced by alkyl)- or -S-.

[0045] In some embodiments, L is C, which is optionally substituted with one or more substituents. 1~6 Alkylene group, C 2~6 Alkenylene group or C2~6 Selected from the alkynylene group, the C 1~6 Alkylene group, C 2~6 Alkenylene group or C 2~6 One or more -CH2- groups in the alkynylene group can be optionally -O-, C 3~9 Cycloalkyl groups, 3-11 member heterocycloalkyl groups, 4-6 member heterocycloalkenyl groups, C6 aryl groups, 5-6 member heteroaryl groups, -NH-, -N(C 1~3 It is replaced by alkyl)- or -S-.

[0046] In some embodiments, L is C, which is optionally substituted with one or more substituents. 1~4 Alkylene group, C 2~4 Alkenylene group or C 2~4 Selected from the alkynylene group, the C 1~4 Alkylene group, C 2~4 Alkenylene group or C 2~4 One or more -CH2- groups in the alkynylene group, for example, one or two, one or three, can be optionally -O-, C 4~6 Cycloalkyl groups, 4-6 member heterocycloalkyl groups, 4-6 member heterocycloalkenyl groups, C6 aryl groups, 5-6 member heteroaryl groups, -NH-, -N(C 1~3 It is replaced by alkyl)- or -S-. In some embodiments, L is C 1~6 Selected alkylene group, the C 1~6 One or more -CH2- groups in the alkylene group can be optionally -O-, C 3~10 Cycloalkyl groups, 4-11 member heterocycloalkyl groups, 4-10 member heterocycloalkenyl groups, -NH-, -N(C 1~3 Replaced by alkyl)- or -S-, the C 1~6 The alkylene group is optionally substituted with one or more substituents.

[0047] In some embodiments, L is C 1~6 Selected alkylene group, the C 1~6One or more -CH2- groups in the alkylene group can be optionally -O-, C 3~10 Cycloalkyl groups, 4-11 member heterocycloalkyl groups, 5-6 member heterocycloalkenyl groups, -NH-, -N(C 1~3 Replaced by alkyl)- or -S-, the C 1~6 The alkylene group is optionally substituted with one or more substituents. In some embodiments, L is -(5-8 membered heterocycloalkyl containing 1-2 N or O atoms)-C 1~6 Alkylene-,-(C 5~8 Cycloalkyl)-C 1~6 Alkylene-,-C 1~6 Alkylene-(5-8 membered heterocycloalkyl group containing 1-2 N or O atoms)-C 1~6 Alkylene-, or -C 1~6 Alkylene-(C) 5~8 Cycloalkyl)-C 1~6 Selected from alkylene.

[0048] In some embodiments, by definition of L, the substituents are halogen, =O, -OH, -NH2, -CN, and C. 1~6 Alkyl alkyl group, C 1~6 Alkoxy group, Halo C 1~6 Alkyl alkyl group, C 1~6 Alkylamino group, diC 1~6 Alkylamino group, C 3~12 Selected from cycloalkyl groups or 4- to 12-membered heterocycloalkyl groups. In some embodiments, in the definition of L, the substituent is halogen, =O, -OH, -NH2, -CN, C 1~4 Alkyl alkyl group, C 1~4 Alkoxy group, Halo C 1~4 Alkyl alkyl group, C 1~4 Alkylamino group, diC 1~4 Alkylamino group, C 3~10 Selected from cycloalkyl groups or 4-10 member heterocycloalkyl groups. In some embodiments, by definition of L, the substituents are halogens, =O, OH, NH2, CN, and C 1~6 Alkyl alkyl group or C 1~6The substituent is selected from alkoxy groups. In some embodiments, by definition of L, the substituent is selected from =O, OH, NH2, halogen, or CN. In some embodiments, by definition of L, the substituent is =O.

[0049] In some embodiments, L is -LNK 1 -Cy 1 -LNK-Cy 2 -LNK 2 -Cy 3 -Selected from, here, Cy 1 Cy 2 or Cy 3 Each of these can be combined, or optionally one or more Rs. a C is replaced by 3~12 Independently selected from cycloalkyl groups, 4-12 membered heterocycloalkyl groups, or 4-12 membered heterocycloalkenyl groups; LNK, LNK 1 and LNK 2 Each of these is a bond, NH, O, S, or optionally one or more R b C is replaced by 1~12 Alkylene group, C 2~12 Alkenylene group, C 2~12 Alkynylene group or C 1~12 Independently selected from heteroalkylene groups; Each R a and each R b These are halogen, =O, -OH, -NH2, -CN, and C respectively. 1~6 Alkyl alkyl group, C 1~6 Alkoxy group, Halo C 1~6 Alkyl alkyl group, C 1~6 Alkylamino group, diC 1~6 Alkylamino group, C 3~12 It is independently selected from cycloalkyl groups or 4- to 12-membered heterocycloalkyl groups.

[0050] In some embodiments, Cy 1 Cy 2 and Cy 3 They are not bonded at the same time. In some embodiments, Cy2 and Cy 3 This is a bond. In some embodiments, LNK 1 and LNK 2 It is a combination.

[0051] In some embodiments, L is -Cy 1 -, -Cy 2 -, -LNK 1 -, -Cy 1 -LNK-, -Cy 1 -Cy 2 -, -LNK 1 -Cy 1 -LNK-, -LNK-Cy 2 -LNK 2 -, -Cy 1 -Cy 2 -LNK 2 -, -LNK 1 -Cy 1 -Cy 2 -, -Cy 1 -LNK-Cy 2 -, -LNK 1 -Cy 1 -Cy 2 -LNK 2 -, -LNK 1 -Cy 1 -LNK-Cy 2 -, -Cy 1 -LNK-Cy 2 -LNK 2 -, -Cy 1 -Cy 2 -Cy 3 -or-Cy 1 -Cy 2 -LNK 2 -Cy 3 - is selected from. In some embodiments, L is -Cy 1 -Selected from. In some embodiments, L is -LNK 1 - is selected from. In some embodiments, L is -Cy 1 Selected from -LNK-

[0052] In some embodiments, LNK, LNK 1 and LNK 2Each of these is a bond, NH, O, S, or optionally one or more R b C is replaced by 1~10 Alkylene group, C 2~10 Alkenylene group, C 2~10 Alkynylene group or C 1~10 Selected independently from heteroalkylene groups. In some embodiments, LNK, LNK 1 and LNK 2 Each of these is a bond, NH, O, S, or optionally one or more R b C is replaced by 1~6 Alkylene group, C 2~6 Alkenylene group, C 2~6 Alkynylene group or C 1~6 Selected independently from heteroalkylene groups. In some embodiments, LNK, LNK 1 and LNK 2 Each of these is a bond, NH, O, S, or optionally one or more R b C is replaced by 1~4 Alkylene group, C 2~4 Alkenylene group, C 2~4 Alkynylene group or C 1~4 Selected independently from heteroalkylene groups. In some embodiments, LNK, LNK 1 and LNK 2 Each of these is a bond, NH, O, S, or optionally one or more R b C is replaced by 1~6 Alkylene group or C 1~6 Selected independently from heteroalkylene groups. In some embodiments, LNK, LNK 1 and LNK 2 Each of these is a bond, NH, O, S, or optionally one or more R b C is replaced by 1~4 Alkylene group or C 1~4 Selected independently from heteroalkylene groups. In some embodiments, LNK, LNK 1 and LNK 2 Each of these is a bond, NH, O, or optionally one or more Rb C is replaced by 1~3 Alkylene group or C 1~3 Selected independently from heteroalkylene groups. In some embodiments, LNK, LNK 1 and LNK 2 Each of these is a bond, NH, O, or optionally one or more R b C is replaced by 1~2 Alkylene group or C 1~2 Selected independently from heteroalkylene groups. In some embodiments, LNK, LNK 1 and LNK 2 Each is independently selected from bond, NH, O, -NHCH2-, -CH2NHCH2-, -CH2-, -CH2CH2-, -C(O)-, or -C(O)CH2-. In some embodiments, LNK, LNK 1 and LNK 2 Each is independent and is a combination. In some embodiments, LNK, LNK 1 and LNK 2 Each of these is independently -CH2-.

[0053] In some embodiments, Cy 1 Cy 2 or Cy 3 Each of these can be combined, or optionally one or more Rs. a C is replaced by 3~11 Independently selected from cycloalkyl groups, 4-12 member heterocycloalkyl groups, or 4-11 member heterocycloalkenyl groups. In some embodiments, Cy 1 Cy 2 or Cy 3 Each of these can be combined, or optionally one or more Rs. a C is replaced by 4~10 Independently selected from cycloalkyl groups, 4-11 member heterocycloalkyl groups, or 5-6 member heterocycloalkenyl groups. In some embodiments, Cy 1 Cy 2 or Cy 3 Each of these can be combined, or optionally one or more Rs.a C is replaced by 4~9 Independently selected from cycloalkyl groups, 4-11 member heterocycloalkyl groups, or 5-6 member heterocycloalkenyl groups. In some embodiments, Cy 1 Cy 2 or Cy 3 Each of these can be combined, or optionally one or more Rs. a C is replaced by 4~6 It is independently selected from cycloalkyl groups, C9 cycloalkyl groups, 4- to 11-membered heterocycloalkyl groups, or 6-membered heterocycloalkenyl groups.

[0054] In some embodiments, Cy 1 Cy 2 or Cy 3 Each of these can be combined, or optionally one or more Rs. a The group is independently selected from the following substituted groups: cyclobutyl group, cyclopentyl group, cyclohexyl group, spirononyl group, azetidinyl group, pyrrolidinyl group, piperidinyl group, tetrahydropyridinyl group, piperazinyl group, monoazaspiroheptyl group, monoazaspirononyl group, diazaspirononyl group, monoazaspirodecyl group, diazaspirodecane, monoazaspirowndecyl group, diazaspiowndecyl group, octahydrocyclopentapyrrolyl group, diazabicyclooctyl group, or monoazabicyclononyl group.

[0055] In some specific embodiments, Cy 1 Cy 2 or Cy 3 Each of these can be combined, or optionally one or more Rs. a Independently selected from 4- to 11-membered heterocycloalkyl groups substituted by Cy 1 Cy 2 or Cy 3 Each of these can be combined, or optionally one or more Rs. a Independently selected from 7-11 member heterocycloalkyl groups substituted by Cy1 Cy 2 or Cy 3 Each of these can be combined, or optionally one or more Rs. a Independently selected from 4- to 6-membered heterocycloalkyl groups substituted by Cy 1 Cy 2 or Cy 3 Each is independent and is a combination. In some embodiments, Cy 1 Cy 2 or Cy 3 Each of these can optionally include one or more Rs. a It is independently selected from the 6-membered heterocycloalkyl groups that are substituted by [the specified compound].

[0056] In some specific embodiments, Cy 1 Cy 2 or Cy 3 Each of these can be combined, or optionally one or more Rs. a The group is independently selected from cyclobutyl, cyclopentyl, cyclohexyl, spirononyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyridinyl, or piperazinyl groups that are substituted by. In some specific embodiments, Cy 1 Cy 2 or Cy 3 Each of these can be combined, or optionally one or more Rs. a The group is independently selected from the monoazaspiroheptyl group, monoazaspirononyl group, diazaspirononyl group, monoazaspirodecyl group, diazaspirodecane, monoazaspirowndecyl group, diazaspiowndecyl group, octahydrocyclopentapyrrolyl group, diazabicyclooctyl group, or monoazabicyclononyl group that are substituted by the above.

[0057] In some embodiments, Cy 1 Cy 2 or Cy 3 These are, respectively, combination and [ka] or [ka] They are selected independently. In some embodiments, Cy 1 Cy 2 or Cy 3 Each is independent of the others. [ka] That is the case. In some embodiments, Cy 1 Cy 2 or Cy 3 Each is independent of the others. [ka] That is the case.

[0058] In some embodiments, each R a and each R b These are halogen, =O, -OH, -NH2, -CN, and C respectively. 1~6 Alkyl alkyl group, C 1~6 Alkoxy group, Halo C 1~6 Alkyl alkyl group, C 1~6 Alkylamino group, diC 1~6 Alkylamino group, C 3~10 Independently selected from cycloalkyl groups or 4-10 member heterocycloalkyl groups. In some embodiments, each R a and each R b These are halogen, =O, OH, NH2, CN, and C respectively. 1~6 Alkyl alkyl group, C 1~6 Alkoxy group, Halo C 1~6 Alkyl alkyl group, C 1~6 Alkylamino group or diC 1~6 Selected independently from alkylamino groups. In some embodiments, each R a and each R b These are halogen, =O, -OH, -NH2, -CN, and C respectively. 1~4 Alkyl alkyl group, C 1~4 Alkoxy group, Halo C 1~4Alkyl alkyl group, C 1~4 Alkylamino group, or diC 1~4 It is selected independently of the alkylamino group.

[0059] In some embodiments, each R a and each R b These are halogen, =O, -OH, -NH2, -CN, or C respectively. 1~3 Selected independently of alkyl groups. In some embodiments, each R a and each R b Each is independently selected from halogen, =O, -OH, -NH2, or -CN. In some embodiments, each R a and each R b Each of them is independent and equals O.

[0060] In some embodiments, L or -LNK 1 - is selected from a bond, -NHCH2-, -CH2NHCH2-, -CH2-, or -C(O)CH2-.

[0061] In some embodiments, L or -Cy 1 -teeth, [ka] or [ka] They are selected from among them.

[0062] In some embodiments, L or -Cy 1 -LNK- is [ka] or [ka] They are selected from among them.

[0063] In some embodiments, L or -Cy1 -Cy 2 -teeth, [ka] or [ka] They are selected from among them.

[0064] In some embodiments, L or -Cy 1 -Cy 2 -Cy 3 -teeth, [ka] or [ka] They are selected from among them.

[0065] In some embodiments, L or -LNK 1 -Cy 1 -LNK- is [ka] or [ka] They are selected from among them.

[0066] In some embodiments, L or -Cy 1 -Cy 2 -LNK 2 -teeth, [ka] or [ka] They are selected from among them.

[0067] In some embodiments, L or -Cy 1 -LNK-Cy2 -teeth, [ka] or [ka] They are selected from among them.

[0068] In some embodiments, L or -LNK 1 -Cy 1 -Cy 2 -LNK 2 -teeth, [ka] or [ka] They are selected from among them.

[0069] In some embodiments, L or -Cy 1 -LNK-Cy 2 -LNK 2 -teeth [ka] That is the case.

[0070] In some embodiments, L is a bond, -NHCH2-, -CH2NHCH2-, -CH2-, -C(O)CH2-, and [ka] [ka] [ka] or [ka] They are selected from among them.

[0071] In some embodiments, L is [ka] or [ka] They are selected from among them.

[0072] In some embodiments, L is [ka] That is the case. In some embodiments, L is [ka] That is the case. In some embodiments, L is [ka] That is the case.

[0073] In some embodiments, the following structural fragment [ka] teeth, [ka] [ka] [ka] or [ka] They are selected from among them.

[0074] In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] They are selected from among them.

[0075] In some embodiments, R f C is substituted with H, fluorine, chlorine, bromine, deuterium, or one or more substituents as optional. 1~3 Selected from alkyl groups. In some embodiments, R f is H, fluorine, chlorine, bromine, deuterium or C 1~3 Selected from alkyl groups, the C 1~3 The alkyl group is optionally substituted with one or more halogens, -OH, -NH2, or -CN. In some embodiments, R f is H, fluorine, chlorine, bromine, deuterium or C 1~3 Selected from alkyl groups. In some embodiments, R f is selected from H, fluorine, deuterium, or a methyl group. In some embodiments, R f H is H.

[0076] In some embodiments, X 5 X is selected from CH or N. In some embodiments, X 5 It is CH.

[0077] In some embodiments, X 6 is -O-, -NH- or -N(C 1~3 Selected from alkyl. In some embodiments, X 6 X is selected from -O- or -N(CH3)-. In some embodiments, X 6 It is -O-.

[0078] In some embodiments, each R 2 , each R 3 and each R4 These are halogen, -OH, -NH2, -CN, and C respectively. 1~6 Alkyl alkyl group, C 1~6 Alkoxy group, or halo C 1~6 A molecule independently selected from alkyl groups, and the aforementioned -OH, -NH2, -CN, C 1~6 Alkyl alkyl group, C 1~6 Alkoxy group, or halo C 1~6 The alkyl group is optionally substituted with one or more substituents. In some embodiments, each R 2 , each R 3 and each R 4 These are halogen, -OH, -NH2, -CN, and C respectively. 1~4 Alkyl alkyl group, C 1~4 Alkoxy group, or halo C 1~4 It is selected independently of alkyl groups.

[0079] In some embodiments, each R 2 These are halogens, -OH, -NH2, -CN, and C 1~3 Alkyl alkyl group, C 1~3 Alkoxy group, or halo C 1~3 Selected independently of alkyl groups. In some embodiments, each R 2 These are halogens, -OH, -NH2, -CN, and C 1~3 Alkyl alkyl group or C 1~3 Selected independently of the alkoxy group. In some embodiments, each R 2 R is independently selected from fluorine, chlorine, bromine, -OH, -NH2, -CN, methyl group, or methoxy group. In some embodiments, each R 2 is independently selected from fluorine, chlorine, bromine, -CN, or methoxy group. In some embodiments, each R 2 is independently selected from -CN or methoxy groups. In some embodiments, each R 2 -CN or C 1~6 Alkoxy groups, for example, C 1~5 Alkoxy group, C 1~4 Alkoxy group or C 1~3 It is selected independently of the alkoxy group.

[0080] In some embodiments, each R 3 These are halogen, -OH, -NH2, -CN, and C respectively. 1~3 Alkyl alkyl group, C 1~3 Alkoxy group, or halo C 1~3 Selected independently of alkyl groups. In some embodiments, each R 3 These are halogen, -OH, -NH2, -CN, or C respectively. 1~3 Selected independently of alkyl groups. In some embodiments, each R 3 These are C 1~6 Alkyl alkyl group, C 1~5 Alkyl alkyl group or C 1~4 Alkyl alkyl group, preferably C 1~3 Selected independently of alkyl groups. In some embodiments, each R 3 Each of these is independently a methyl group.

[0081] In some embodiments, each R 4 These are halogen, -OH, -NH2, -CN, and C respectively. 1~3 Alkyl alkyl group, C 1~3 Alkoxy group, or halo C 1~3 Selected independently of alkyl groups. In some embodiments, each R 4 These are halogen, -OH, -NH2, -CN, or C respectively. 1~3 Selected independently of alkyl groups. In some embodiments, each R 4 Each of these is independently selected from fluorine, chlorine, bromine, -OH, -NH2, or -CN.

[0082] In some embodiments, m is selected from 0, 1, 2, or 3. In some embodiments, m is selected from 1, 2, or 3. In some embodiments, m is 2. In some embodiments, p is selected from 1, 2, 3, or 4. In some embodiments, p is selected from 3 or 4. In some embodiments, p is 4. In some embodiments, q is selected from 0, 1, 2, or 3. In some embodiments, q is selected from 0 or 1. In some embodiments, q is 0.

[0083] In some embodiments, the following structural fragment [ka] teeth, [ka] That is the case.

[0084] In some embodiments, ring G is selected from a phenyl group or a 5-6 membered heteroaryl group. In some embodiments, ring G is selected from a phenyl group or a 6 membered heteroaryl group (a 6 membered heteroaryl group containing 1-2 N atoms). In some embodiments, ring G is a phenyl group.

[0085] In some embodiments, ring E is C 3~9 Selected from cycloalkyl groups or 3- to 9-membered heterocycloalkyl groups. In some embodiments, ring E is C 4~9 Selected from cycloalkyl groups or 4- to 9-membered heterocycloalkyl groups. In some embodiments, ring E is C 4~7 Selected from cycloalkyl groups or 4- to 7-membered heterocycloalkyl groups. In some embodiments, ring E is C 4~7 Cycloalkyl groups, for example, C 4~6 Cycloalkyl groups, C 4~5It is selected from cycloalkyl groups. In some embodiments, ring E is selected from a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group.

[0086] In some embodiments, ring E is a cyclobutyl group. In some embodiments, ring E is [ka] That is the case. In some embodiments, ring E is [ka] That is the case. In some embodiments, the following structural parts [ka] teeth, [ka] That is the case. In some embodiments, the following structural parts [ka] teeth, [ka] That is the case.

[0087] In some embodiments, ring F is C 6~10It is selected from an aryl group or a 5- to 7-membered heteroaryl group. In some embodiments, ring F is selected from a phenyl group or a 5- to 6-membered heteroaryl group. In some embodiments, ring F is selected from a phenyl group or a 6-membered heteroaryl group, for example, a 6-membered heteroaryl group containing 1 to 3 or 1 to 2 N atoms. In some embodiments, ring F is selected from a phenyl group, a pyridinyl group, a pyridazinyl group, a pyrimidinyl group, or a pyrazinyl group. In some specific embodiments, ring F is a phenyl group. In some embodiments, ring F is a pyridinyl group. In some embodiments, ring F is a pyrimidinyl group. In some embodiments, ring F is a pyridazinyl group. In some embodiments, ring F is, [ka] or [ka] They are selected from among them. In some embodiments, ring F is [ka] That is the case. In some embodiments, ring F is [ka] That is the case. In some embodiments, ring F is [ka] That is the case. In some embodiments, ring F is [ka] That is the case. In some embodiments, ring F is [ka] That is the case.

[0088] In some embodiments, [ka] teeth, [ka] or [ka] They are selected from among them.

[0089] In some embodiments, R t is hydrogen, -OH, C 1~4 Alkyl alkyl group, C 3~6 Selected from cycloalkyl groups or 3-6 member heterocycloalkyl groups, the C 1~4 Alkyl alkyl group, C 3~6 A cycloalkyl group or a 3- to 6-membered heterocycloalkyl group is optionally substituted. In some embodiments, R t is hydrogen, -OH, C 1~3 Alkyl alkyl group, C 3~4 Selected from cycloalkyl groups or 3-4 member heterocycloalkyl groups, the C 1~3 Alkyl alkyl group, C 3~4 A cycloalkyl group or a 3-4 member heterocycloalkyl group is optionally substituted. In some embodiments, R t is hydrogen, or C 1~3 Alkyl groups, for example, selected from methyl, ethyl, and propyl groups. In some embodiments, R t It is hydrogen.

[0090] In some embodiments, "optionally substituted" means being optionally substituted with one or more halogens, such as fluorine, chlorine, bromine, or iodine, -CN, -OH, or -NH2.

[0091] In some embodiments, the following structural fragment [ka] teeth, [ka] They are selected from among them. In some embodiments, the following structural fragment [ka] teeth, [ka] They are selected from among them. In some embodiments, the following structural fragment [ka] teeth, [ka] They are selected from among them. In some embodiments, the following structural fragment [ka] teeth, [ka] They are selected from among them. In some embodiments, the following structural fragment [ka] teeth, [ka] They are selected from among them. In some embodiments, the following structural fragment [ka] teeth, [ka] They are selected from among them. In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] They are selected from among them. In some embodiments, the following structural fragment [ka] or [ka] teeth, [ka] That is the case.

[0092] In some embodiments, the heterocycloalkenyl group, heteroaryl group, heterocycloalkyl group, or heteroalkylene group contains one or more heteroatoms or heteroatom groups independently selected from -O-, -NH-, -N-, -S-, C=O, -C(=O)NH-, -C(=O)O-, -S(=O)-, or -S(=O)2-. In some embodiments, the heterocycloalkenyl group, heteroaryl group, heterocycloalkyl group, or heteroalkylene group contains one or more heteroatoms or heteroatom groups independently selected from -O-, -NH-, -N-, or -S-. In some embodiments, the heterocycloalkenyl group, heteroaryl group, heterocycloalkyl group, or heteroalkylene group contains one or more heteroatoms or heteroatom groups independently selected from -O-, -NH-, or -N-. In some embodiments, the number of heteroatoms or heteroatom groups is independently selected from 1, 2, 3, 4, 5, or 6, or selected from 1, 2, 3, or 4, or selected from 1, 2, or 3, or selected from 1 or 2.

[0093] In some embodiments, the heteroatoms in the heterocycloalkenyl group are selected from N, NH, O, or S. In some embodiments, the heteroatoms in the heterocycloalkenyl group are selected from N, O, or S. In some specific embodiments, the heteroatoms in the heterocycloalkenyl group are selected from N or O. In some embodiments, the number of heteroatoms in the heterocycloalkenyl group is selected from 1, 2, 3, 4, 5, or 6. In some embodiments, the number of heteroatoms in the heterocycloalkenyl group is selected from 1, 2, 3, or 4. In some embodiments, the number of heteroatoms in the heterocycloalkenyl group is selected from 1, 2, or 3. In some specific embodiments, the number of heteroatoms in the heterocycloalkenyl group is selected from 1 or 2.

[0094] Any embodiment of the above-described compound and specific rings A, B, C, E, F, G, R in the above-described compound as herein 1 , R 2 , R 3 , R 4 , R t L, X 5 , X 6 It should be understood that any specific substituent described with respect to substituents can independently be combined with substituents of other embodiments of the present application and / or compounds to form embodiments of the present invention not specifically described above. Also, any specific ring A, ring B, ring C, ring E, ring F, ring G, R in specific embodiments and / or claims 1 , R 2 , R 3 , R 4 , R t L, X 5 , X 6 It should be understood that when a range of substituents is disclosed with respect to substituents, one or more substituents may be removed from that range, and the remaining range of substituents will also be considered embodiments of the present application.

[0095] This application relates to compounds of formula I-1 or formula I-1A, their stereoisomers, or pharmaceutically acceptable salts thereof. [ka] In the formula, ring A, ring B, ring C, ring F, R 1 , n, R 2 , m, R 3 , p, R 4 q, X 5 , X 6 The definition of L is as described in this application.

[0096] In some embodiments, the following structural parts [ka] This is explained in this application.

[0097] This application relates to compounds of formula I-2, formula I-2A, formula I-3, or formula I-3A, their stereoisomers, or pharmaceutically acceptable salts thereof. [ka] , or [ka] In the formula, ring A, ring B, ring C, ring F, R 1 , n, R 2 , m, R 3 , p, R 4 q, X 5 The definition of L is as described herein; X is selected from CH or N.

[0098] In some embodiments, the definitions of the following structural fragments are as described herein. [ka]

[0099] In some embodiments, optionally, the compounds described in this application are not the following compounds. [ka]

[0100] In some embodiments, optionally, the compounds described in this application are not the following compounds. [ka] or [ka]

[0101] In some embodiments, optionally, the compounds described in this application are not the following compounds. [ka] or [ka]

[0102] In some embodiments, the structural part [ka] or [ka] teeth, [ka] or [ka] They won't be chosen.

[0103] In some embodiments, the structural part [ka] or [ka] teeth, [ka] or [ka] They won't be chosen. In some embodiments, the structural part [ka] or [ka] teeth, [ka] or [ka] They won't be chosen.

[0104] In some embodiments, the structural part [ka] or [ka] teeth, [ka] or [ka] They won't be chosen. In some embodiments, the structural part [ka] or [ka] teeth, [ka] or [ka] They won't be chosen. In some embodiments, the structural part [ka] or [ka] teeth, [ka] or [ka] They won't be chosen.

[0105] In another embodiment, the present application relates to compounds of formula I' or formula I'', moieties, stereoisomers thereof, derivatives, specifically, for example, Protac molecules, or pharmaceutically acceptable salts thereof. [ka] In the formula, ring A does not exist, or C 5~10 Selected from a cycloalkenyl group, a 5-10 member heterocycloalkenyl group, a phenyl group, or a 5-6 member heteroaryl group; Ring B is a phenyl group; Ring C is selected from an isoxazolyl group or a furyl group; L is a linking functional group; optionally, the definition of L is as described herein; optionally, R 1 The definitions of n and n are as described herein.

[0106] In some embodiments, the present application relates to the following parts, or compounds containing such parts (including the Protac molecule), stereoisomers thereof, or pharmaceutically acceptable salts thereof. [ka] Here, the definition of L is as explained above, and Y 6 C(R 5 ) or N, R 5 H, deuterium, tritium, C 1~3 The alkyl group is =O; preferably H, and d and d' may be the same or different, and each is independently 1, 2, or 3.

[0107] In some embodiments, the present application relates to the following parts, or compounds containing such parts (including the Protac molecule), stereoisomers thereof, or pharmaceutically acceptable salts thereof. [ka] Here, L, Y 6 The definitions of d and d' are as described herein, Y 5 C(R 5 ) or N, R 5 H, deuterium, tritium, C 1~3 The alkyl group is =O, preferably H.

[0108] In some embodiments, the following structural components are described in this application. [ka]

[0109] In another embodiment, the present application relates to compounds, parts, stereoisomers, derivatives thereof of formula I'-a or formula I''-a, specifically, for example, Protac molecules, or pharmaceutically acceptable salts thereof. [ka] In the formula, ring A does not exist, or C 5~10 Selected from a cycloalkenyl group, a 5-10 member heterocycloalkenyl group, a phenyl group, or a 5-6 member heteroaryl group; Ring B is a phenyl group; Ring C is selected from an isoxazolyl group or a furyl group; Each R 1a Halogen, -OH, -NH2, -CN, =O, -CHO, C 1~4 Alkyl alkyl group, C 1~4 Alkoxy group, C 1~6 Alkyl OC(O)-, C 3~12 A cycloalkyl group is independently selected from cycloalkyl groups or 4-12 member heterocycloalkyl groups, and the C 1~4 Alkyl alkyl group, C 1~4 Alkoxy group, C3~12 Cycloalkyl groups or 4- to 12-membered heterocycloalkyl groups may optionally contain one or more halogens, =O, -OH, -NH2, -CN, CHO, COOH, -C 1~4 alkyl-OH, C 1~6 Alkyl OC(O)-, or optionally C 1~6 Substituted by 4- to 10-membered heterocycloalkyl groups substituted with alkylCOC(O)-; n is selected from 0, 1, 2, or 3.

[0110] In some embodiments, ring A is absent, or C 5~7 Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, a phenyl group, or a 5- to 6-membered heteroaryl group.

[0111] In some embodiments, ring A is absent, or C 5~6 Selected from a cycloalkenyl group, a 5-10 member heterocycloalkenyl group, a phenyl group, or a 5-6 member heteroaryl group.

[0112] In some embodiments, ring A is absent, or C 5~6 Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, a phenyl group, or a 5- to 6-membered heteroaryl group.

[0113] In some embodiments, ring A is absent, or C 5~6 Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, a phenyl group, or a 5-membered heteroaryl group.

[0114] In some embodiments, ring A is absent, or C 5~6 Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, a phenyl group, a pyrrolyl group, a pyrazolyl group, a furyl group, or an oxazolyl group.

[0115] In some embodiments, ring A is absent or selected from a C5 cycloalkenyl group, a C6 cycloalkenyl group, a 5-membered, 6-membered, 7-membered, 8-membered or 9-membered heterocycloalkenyl group, a phenyl group, a pyrrolyl group, a pyrazolyl group, a furyl group or an oxazolyl group.

[0116] In some embodiments, ring A is absent or selected from a cyclopentenyl group, a monocyclohexenyl group, a bicyclohexenyl group, a dihydropyrrolyl group, a tetrahydropyridinyl group, a tetrahydroazepinyl group, an azaspirooctenyl group, an azaspirononenyl group, a phenyl group, a pyrrolyl group, a pyrazolyl group, a furyl group, an oxazolyl group, or a dihydrooxazinyl group.

[0117] In some specific embodiments, ring A is C 5~9 Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, a phenyl group, or a 5-membered heteroaryl group.

[0118] In some specific embodiments, ring A is C 5~6 Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, a phenyl group, or a 5-membered heteroaryl group.

[0119] In some specific embodiments, ring A is C 5~9 Selected from a cycloalkenyl group or a 5- to 9-membered heterocycloalkenyl group. In some specific embodiments, ring A is C 5~6 Selected from a cycloalkenyl group or a 5- to 9-membered heterocycloalkenyl group.

[0120] In some specific embodiments, ring A is C 5~9 Selected from cycloalkenyl groups. In some specific embodiments, ring A is C 5~6 It is selected from cycloalkenyl groups. In some specific embodiments, ring A is selected from 5- to 9-membered heterocycloalkenyl groups.

[0121] In some specific embodiments, ring A is selected from a cyclopentenyl group, a dihydropyrrolyl group, a tetrahydropyridinyl group, a tetrahydroazepinyl group, an azaspirononenyl group, an azaspirooctenyl group, a phenyl group, a pyrrolyl group, or a pyrazolyl group.

[0122] In some specific embodiments, ring A is selected from a cyclopentenyl group, a dihydropyrrolyl group, a tetrahydropyridinyl group, a tetrahydroazepinyl group, an azaspirononenyl group, or an azaspirooctenyl group.

[0123] In some specific embodiments, ring A is selected from a cyclopentenyl group. In some specific embodiments, ring A is selected from a dihydropyrrolyl group, a tetrahydropyridinyl group, a tetrahydroazepinyl group, or azaspirooctene.

[0124] In some specific embodiments, ring A is selected from a phenyl group, a pyrrolyl group, or a pyrazolyl group.

[0125] In some embodiments, ring A is [ka] or [ka] They are selected from among them.

[0126] In some specific embodiments, ring C is an isoxazolyl group. In some specific embodiments, ring C is a furyl group.

[0127] In some embodiments, the following structural parts [ka] teeth, [ka] or [ka] They are selected from among them.

[0128] In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] They are selected from among them. In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] Selected from; or the following structural fragments [ka] teeth, [ka] or [ka] Selected from; or the following structural fragments [ka] teeth, [ka] They are selected from among them.

[0129] In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] They are selected from among them. In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] Selected from; or the following structural fragments [ka] teeth, [ka] or [ka] Selected from; or the following structural fragments [ka] teeth, [ka] That is the case.

[0130] In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] They are selected from among them. In some specific embodiments, the following structural fragment [ka] teeth, [ka] or [ka] They won't be chosen.

[0131] In some embodiments, the following structural fragment [ka] teeth, [ka] or [ka] They are selected from among them. In some embodiments, each R 1a These are halogens, -OH, -NH2, -CN, -CHO, and C 1~6 Alkyl OC(O)-, C 1~4 Alkyl alkyl group, C 1~4 Alkoxy group, C 3~10 A cycloalkyl group is independently selected from cycloalkyl groups or 4-10 member heterocycloalkyl groups, and the C 1~4 Alkyl alkyl group, C 1~4Alkoxy group, C 3~10 Cycloalkyl groups or 4-10 member heterocycloalkyl groups may optionally contain one or more halogens, =O, -OH, -NH2, -CN, -CHO, -COOH, -C 1~4 alkyl-OH, C 1~6 Alkyl OC(O)-, or optionally C 1~6 Substituted by 4- to 10-membered heterocycloalkyl groups, which are themselves substituted with alkyl COC(O)- groups.

[0132] In some embodiments, each R 1a These are halogens, -OH, -NH2, -CN, -CHO, and C 1~4 Alkyl OC(O)-, C 1~3 Alkyl alkyl group, C 1~3 Alkoxy group, C 3~9 A cycloalkyl group is independently selected from cycloalkyl groups or 4- to 9-membered heterocycloalkyl groups, and the C 1~3 Alkyl alkyl group, C 1~3 Alkoxy group, C 3~9 The cycloalkyl group or 4- to 9-membered heterocycloalkyl group may optionally contain one or more halogens, -OH, =O, -NH2, -CN, -CHO, -COOH, or -C 1~4 alkyl-OH, C 1~4 Alkyl OC(O)-, or optionally C 1~4 Substituted by 4- to 9-membered heterocycloalkyl groups, which are substituted by alkyl COC(O)- groups.

[0133] In some embodiments, each R 1a These are halogens, -OH, -NH2, -CN, -CHO, and C 1~6 Alkyl OC(O)-, C 1~3 Alkyl alkyl group, C 1~3 Alkoxy group, C 3~6 A cycloalkyl group is independently selected from cycloalkyl groups or 4-6 member heterocycloalkyl groups, and the C 1~3 Alkyl alkyl group, C 1~3 Alkoxy group, C 4~6Cycloalkyl groups or 4-6 member heterocycloalkyl groups may optionally contain one or more halogens, -OH, =O, -NH2, -CN, -CHO, -COOH, -C 1~4 alkyl-OH, C 1~6 Alkyl OC(O)-, or optionally C 1~6 Substituted by 3- to 6-membered heterocycloalkyl groups, which are themselves substituted by alkyl COC(O)- groups.

[0134] In some embodiments, each R 1a These are halogens, -OH, -NH2, -CN, -CHO, and C 1~4 Alkyl OC(O)-, C 1~3 A C is independently selected from alkyl groups or 4-6 member heterocycloalkyl groups. 1~3 Alkyl groups or 4-6 member heterocycloalkyl groups may optionally have one or more -OH, =O, -NH2, -CN, -CHO, -COOH, C 1~4 Alkyl OC(O)-, or optionally C 1~4 Substituted by 4- to 6-membered heterocycloalkyl groups, which are themselves substituted with alkyl OC(O)- groups.

[0135] In some embodiments, each R 1a These are halogen, -OH, -CHO, (CH3)3COC(O)-, C 1~3 A C is independently selected from an alkyl group, a cyclobutyl group, or a piperidinyl group. 1~3 The alkyl group, cyclobutyl group, or piperidinyl group may be optionally substituted with one or more -OH, (CH3)3COC(O)-, or a cyclobutyl group optionally substituted with (CH3)3COC(O)-.

[0136] In some embodiments, each R 1a These are F, -OH, -CHO, (CH3)3COC(O)-, -CH2OH, and [ka] or [ka] Selected independently

[0137] In some embodiments, n is selected from 0, 1, or 2. In some embodiments, n is selected from 0 or 1. In some embodiments, n is 0.

[0138] This application relates to the following compounds, parts, stereoisomers, derivatives, specifically, for example, the Protac molecule, or pharmaceutically acceptable salts thereof. [ka] [ka] [ka] Or, [ka] [ka] or [ka]

[0139] In some embodiments, the present application relates to a compound of formula I, its stereoisomer or pharmaceutically acceptable salt thereof, wherein ring A is C 5~10 A cycloalkenyl group, or a 5-15 membered heterocycloalkenyl group containing 1-2 heteroatoms selected from N or O, for example, C 5~8 A cycloalkenyl group, or a 5-8 membered heterocycloalkenyl group containing 1-2 heteroatoms selected from N or O; ring B is a phenyl group; ring C is a 5-6 membered heteroaryl group containing 1-2 heteroatoms selected from N or O; n is 0; X 5 C(R f ) selected from Rf is H, deuterium, or C 1~6 Selected from alkyl groups; L is C 1~10 It is an alkylene group, and the C 1~10 One or more -CH2- groups in the alkylene group are optionally C 5~8 Replaced by a cycloalkyl group, or a 5-8 membered heterocycloalkyl group containing 1-3 or 1-2 N or O atoms; Each R 2 These are independently -OH, -NH2, -CN, and C 1~10 Alkyl alkyl group, C 1~10 Alkoxy group, or halo C 1~10 It is an alkyl group; each R 3 They are independent of halogen and C 1~10 Alkyl alkyl group, or halo C 1~10 It is an alkyl group; q is 0, m is 0, 1, 2 or 3, and p is 0, 1, 2, 3 or 4; X 6 is -O- or -NH-, and ring G is a phenyl group or a 6-membered heteroaryl group containing 1-2 N or O atoms; ring E is C 3~6 It is a cycloalkyl group; ring F is a phenyl group, or a 6-membered heteroaryl group containing 1 to 3 or 1 to 2 N or O atoms; R t is hydrogen, -OH or C 1~6 It is an alkyl group.

[0140] In some embodiments, this application relates to the following compounds, their stereoisomers, or pharmaceutically acceptable salts thereof: [ka] In the formula, each R 2 These are independently -NH2, -CN, and C 1~6 Alkyl alkyl group, C 1~6 Alkoxy group, or halo C 1~6 Alkyl groups, for example, -CN, C 1~6 Alkoxy group, C 1~5 Alkoxy group, C 1~4 Alkoxy group or C 1~3 It is an alkoxy group; Each R 3 C 1~6 Alkyl alkyl group, or halo C 1~6 Alkyl alkyl groups, for example, C 1~6 Alkyl alkyl group, C 1~5 Alkyl alkyl group, C 1~4 Alkyl alkyl group or C 1~3 It is an alkyl group; m is 1, 2, or 3, preferably 1 or 2, and p is 0, 1, 2, 3, or 4, preferably 2, 3, or 4; X 6 is -O- or -NH-, preferably -O-; R t is hydrogen, -OH or C 1~6 It is an alkyl group, preferably hydrogen; Ring F is C 6~10 The group is an aryl group or a 6- to 10-membered heteroaryl group, preferably a phenyl group or a 6-membered heteroaryl group containing 1 to 4, 1 to 3, or 1 to 2 nitrogen atoms; L is C 1~6 It is an alkylene group, and the C 1~6 One or more -CH2- groups in the alkylene group are optionally a 5-7 member heterocycloalkyl group containing 1-3 or 1-2 N atoms, for example, [ka] Preferably [ka] Replaced by; Ring A is C 5~9 A cycloalkenyl group, or a 5-9 membered heterocycloalkenyl group containing 1-2 N atoms, preferably C 5~7 It is a cycloalkenyl group, or a 5-7 member heterocycloalkenyl group containing one N atom.

[0141] In some embodiments, this application relates to the following compounds, their stereoisomers, or pharmaceutically acceptable salts thereof: [ka] Preferably, [ka] or [ka] And, In the formula, R 2 , R 3 , m, p, X 6 , R t The definitions of rings F, L, and A are as described above, and each R 2 Each R can be the same or different, 3 They may be the same or different; Y 1 , Y 2 , Y 3 , Y 4 , Y 5 and Y 6 Each of them is independent of C(R 5 ) or N, R 5 H, deuterium, tritium, C 1~3 Alkyl alkyl group =O, preferably H, deuterium, or tritium; d and d' may be the same or different, each independently being 1, 2, or 3. In some preferred embodiments, the Y 1 , Y 2 , Y 3 and Y 4 Up to three of these are N, and more preferably, Y 1 , Y 2 , Y 3 and Y 4 A maximum of two of these are N.

[0142] In some embodiments, Y 1 is CH or N. In some embodiments, Y 1 CH is CH. In some embodiments, Y 1 It is N.

[0143] In some embodiments, Y 2is CH or N. In some embodiments, Y 2 CH is CH. In some embodiments, Y 2 It is N.

[0144] In some embodiments, Y 3 is CH or N. In some embodiments, Y 3 CH is CH. In some embodiments, Y 3 It is N.

[0145] In some embodiments, Y 4 is CH or N. In some embodiments, Y 4 CH is CH. In some embodiments, Y 4 It is N.

[0146] In some embodiments, Y 5 is CH or N. In some embodiments, Y 5 CH is CH. In some embodiments, Y 5 It is N.

[0147] In some embodiments, Y 6 is CH or N. In some embodiments, Y 6 CH is CH. In some embodiments, Y 6 It is N.

[0148] In another embodiment, the present application relates to the use of the compound, for example, formula I' or formula I'' or formula I'-a or formula I''-a or a specific compound, part, its isomer, for example, a stereoisomer, or its derivative in the production of a Protac molecule. In another embodiment, the present application relates to the use of the compound, for example, formula I' or formula I'' or formula I'-a or formula I''-a or a specific compound, part, its isomer, for example, a stereoisomer, or its derivative to constitute a part of a Protac molecule. In another embodiment, the present application relates to the compound, for example, formula I' or formula I'' or formula I'-a or formula I''-a or a specific compound, part, its isomer, for example, a stereoisomer, or its derivative in the form of a Protac molecule. In another embodiment, the present application relates to the use of the compound, for example, formula I' or formula I'' or formula I'-a or formula I''-a or a specific compound, part, its isomer, for example, stereoisomer, its derivative, for degrading a protein, for example, AR, for example, the compound, for example, formula I' or formula I'' or formula I'-a or formula I''-a or a specific compound, part, its isomer, for example, stereoisomer, its derivative, degrading the protein in the form of a Protac molecule. In another embodiment, the present application relates to the use of the compound, for example, formula I' or formula I'' or formula I'-a or formula I''-a or a specific compound, part, its isomer, for example, stereoisomer, its derivative, for degrading a protein in the form of a Protac molecule. The present application relates to the use of the compound, for example, formula I' or formula I'' or formula I'-a or formula I''-a or a specific compound, part, its isomer, for example, stereoisomer, its derivative, for example, as a manufacturing intermediate in the production of a Protac molecule. This application relates to the use of the aforementioned compound, for example, formula I' or formula I'' or formula I'-a or formula I''-a, or a specific compound, part thereof, its isomer, for example, stereoisomer, its derivative, for example, as a manufacturing intermediate, in the production of a proteolytic agent.

[0149] This application relates to the following compounds, their stereoisomers, or pharmaceutically acceptable salts thereof. [ka] [ka] [ka] [ka] [ka] or [ka]

[0150] This application further relates to the following compounds, their stereoisomers, or pharmaceutically acceptable salts thereof. [ka] [ka] [ka] [ka] [ka] or [ka]

[0151] This application further includes embodiments obtained by arbitrarily combining, deleting, or replacing the above embodiments.

[0152] In another embodiment, the present application relates to a pharmaceutical composition comprising the above-mentioned compound of the present application, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof; optionally, the pharmaceutical composition of the present application further comprises a pharmaceutically acceptable additive.

[0153] In another embodiment, the present application relates to the use of the above-mentioned compound, its stereoisomer, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, in the manufacture of a drug for preventing or treating a medical condition that is treated by degrading a target protein, such as an androgen receptor (AR), which binds to a targeted ligand.

[0154] In another embodiment, the present application relates to the use of the above-mentioned compound, its stereoisomer, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, in the manufacture of a drug for preventing or treating a medical condition treated by binding to cereblon (CRBN) in vivo.

[0155] In another embodiment, the present application relates to the use of the above-mentioned compound, its stereoisomer, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof in the manufacture of a drug for preventing or treating AR-related diseases.

[0156] The present application relates to a method for treating or preventing a mammalian disease that is treated by degrading a target protein, such as an androgen receptor (AR), which binds to a targeted ligand, comprising administering a therapeutically effective amount of the above-mentioned compound of the present application, its stereoisomer, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, to a mammal, preferably a human, that is in need of such treatment.

[0157] The present application relates to a method for treating or preventing a medical condition treated by binding to cereblon in vivo, comprising administering a therapeutically effective amount of the above-mentioned compound of the present application, its stereoisomer, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, to a mammal, preferably a human, that is in need of such treatment.

[0158] In another embodiment, the present application relates to a method for treating AR-related diseases in mammals, comprising administering to a mammal in need of such treatment, preferably a human, a therapeutically effective amount of the above-mentioned compound of the present application, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0159] In another embodiment, the present application relates to the above-mentioned compounds, stereoisomers thereof, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, for preventing or treating conditions treated by degrading target proteins that bind to targeted ligands, such as androgen receptors (ARs).

[0160] In another embodiment, the present application relates to the above-mentioned compound, its stereoisomer, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for preventing or treating a medical condition treated by binding to cereblon in vivo.

[0161] In another embodiment, the present application relates to the above-mentioned compounds, stereoisomers thereof, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, for the prevention or treatment of AR-related diseases.

[0162] In another embodiment, the present application relates to the use of the above-mentioned compounds, their stereoisomers, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, in the prevention or treatment of medical conditions treated by degrading target proteins that bind to targeted ligands, such as androgen receptors (ARs).

[0163] In another embodiment, the present application relates to the use of the above-mentioned compound, its stereoisomer, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, in the prevention or treatment of a medical condition treated by binding to cereblon in vivo.

[0164] In another embodiment, the present application relates to the use of the above-mentioned compounds, their stereoisomers, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, in the prevention or treatment of AR-related diseases.

[0165] In some specific embodiments, the above AR-related disease is selected from conditions treated by degrading and / or inhibiting androgen receptors (ARs), which are proteins that bind to AR target protein ligands. In some specific embodiments, the above AR-related disease is selected from conditions treated by binding to cereblon in vivo. In some embodiments, the above disease or condition is selected from cancers, such as prostate cancer.

[0166] In some specific embodiments, the medical conditions treated by binding to cereblon in vivo and / or by degrading target proteins that bind to targeted ligands are selected from AR-related diseases. In some specific embodiments, the AR-related diseases are selected from cancers, such as prostate cancer.

[0167] In this specification, “one or more” means an integer from 1 to 10. For example, “one or more” means 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, “one or more” is selected from 1, 2, 3, 4, 5, or 6. In some embodiments, “one or more” is selected from 1, 2, or 3. In some embodiments, “one or more” is selected from 1 or 2.

[0168] In some embodiments, the present application includes the variables defined above and their embodiments, as well as any combination thereof. [Effects of the Invention]

[0169] The compound of the present invention has proteolytic activity against AR or its variants, and antiproliferative activity against related cells, for example, it has proteolytic activity against AR in VCaP cells and / or AR in MDA-PCA-2B cells (including its L702H and / or T878A mutation), AR in 22RV1 cells (including its H875Y and / or ARV7 mutation), AR in HEK293 cells (including its L702H mutation), and / or AR in LNCaP cells (including its T878A mutation), and also has antiproliferative activity against VCaP cells and / or LNCaP cells (including its T878A mutation), and / or 22RV1 cells (including its H875Y and / or ARV7 mutation), and / or MDA-PCA-2B cells (including its L702H and / or T878A mutation), and / or HEK293 cells (including its L702H mutation). Furthermore, the compound exhibits good in vitro stability in liver microsomes and good in vivo pharmacokinetic properties in mammals, such as mice, specifically AUC, t 1 / 2 It also possesses parameters such as those mentioned above, and can suppress tumor growth in vivo, thus demonstrating drug potential.

[0170] (definition) Unless otherwise specified, terms used in this application have the following meanings. Unless otherwise specified, certain terms are understood in the ordinary sense of the art, rather than as undefined or ambiguous. Where a trade name appears herein, it refers to the corresponding product or its active ingredient.

[0171] Unless otherwise specified, [ka] teeth, [ka] This indicates that any hydrogen atom at any point in the functional group may be substituted by a functional group linked with a "-".

[0172] The term "substituted" refers to the substitution of any one or more hydrogen atoms in a given atom by a substituent, provided that the atom's valence remains normal and the resulting compound is stable. If the substituent is oxo (i.e., =O), two hydrogen atoms are substituted. Oxygen substitution does not occur in aryl groups.

[0173] The terms “optional” or “optionally” mean that the following matters or circumstances may or may not occur, and such descriptions include cases where such matters or circumstances occur and cases where such matters or circumstances do not occur. “Optionally substituted” includes both being unsubstituted and being substituted. For example, “optionally” substituted of an ethyl group with a halogen means that the ethyl group may not be substituted (CH2CH3), may be monosubstituted (e.g., CH2CH2F), may be polysubstituted (e.g., CHFCH2F, CH2CHF2, etc.), or may be completely substituted (CF2CF3). It is understandable to those skilled in the art that there are no substitutions or substitution methods for any functional group containing one or more substituents that are spatially impossible and / or cannot be synthesized.

[0174] In this specification, "C m~n " means that the part in question has an integer number of carbon atoms within a predetermined range. For example, "C 1~6 " " refers to the fact that the functional group may have one carbon atom, two carbon atoms, three carbon atoms, four carbon atoms, five carbon atoms, or six carbon atoms.

[0175] If a variable (e.g., R) appears one or more times in the composition or structure of a compound, each instance is defined independently. For example, if a functional group contains two Rs, each R has an independent choice.

[0176] When a bond intersects and connects to two atoms in a ring (including monocyclic, fused, or spirocyclic rings), such a bond can connect to any atom in the ring (including monocyclic, fused, or spirocyclic rings). For example, the following structural unit represents one in which the bonds on both sides can connect to any two different atoms in ring A, ring B, or ring C. [ka] As another example, [ka] This represents a configuration where the bonds on both sides can be linked to any two different atoms in ring A, the intermediate benzene ring, or ring C. As another example, [ka] This represents a configuration where the bonds on both sides can connect to any two different atoms of the four rings in that system.

[0177] The term "halo" or "halogen" refers to fluorine, chlorine, bromine, and iodine. The term "hydroxyl group" refers to the -OH functional group. The term "amino group" refers to the -NH2 functional group. The term "cyano group" refers to the -CN functional group.

[0178] The term "alkyl group" refers to a group whose general formula is C n H 2n+1 This refers to a hydrocarbon group. The alkyl group can be either linear or branched. For example, "C 1~6The term "alkyl group" refers to alkyl groups containing 1 to 6 carbon atoms, such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, neopentyl group, hexyl group, and 2-methylpentyl group. Similarly, the alkyl group portion of alkoxy groups, alkylamino groups, dialkylamino groups, alkylsulfonyl groups, and alkylthio groups, i.e., alkyl groups, have the same definition as above.

[0179] The term "alkylene group" refers to a divalent functional group formed by removing one hydrogen atom from any position in an alkyl group. For example, "C 1~6 The term "alkylene group" refers to an alkylene group containing 1 to 6 carbon atoms. 1~4 The term "alkylene group" refers to an alkylene group containing 1 to 4 carbon atoms, including, but not limited to, -CH2-, -CH2CH2-, -CH2CH2CH2-, or -CH2CH2CH2CH2-.

[0180] The term "alkenylene group" refers to a divalent functional group formed by removing one hydrogen atom from any position on an alkenyl group. For example, "C 2~6 The term "alkenylene group" refers to an alkenylene group containing 2 to 6 carbon atoms. 2~4 The term "alkenylene group" refers to an alkenylene group containing 2 to 4 carbon atoms, including, but not limited to, -CH2CH=CH-, -CH2CH2CH=CH-, or -CH2CH=CHCH2-.

[0181] The term "alkynylene group" refers to a divalent functional group formed by removing one hydrogen atom from any position on an alkynyl group. For example, "C 2~6 The term "alkylylene group" refers to an alkylylene group containing 2 to 6 carbon atoms. 2~4 The term "alkylylene group" refers to an alkylylene group containing 2 to 4 carbon atoms. [ka] or [ka] This includes, but is not limited to, those listed above.

[0182] The term "heteroalkyl group" refers to a linear or branched alkyl group consisting of a predetermined number of carbon atoms and at least one heteroatom; the chain preferably has 1 to 14 carbon atoms, more preferably 1 to 10 carbon atoms, even more preferably 1 to 6 carbon atoms, most preferably 1 to 3 carbon atoms, and preferably 1, 2, or 3 heteroatoms selected from S, O, and N. For example, C m A heteroalkyl group represents an alkyl group in which a heteroatom is inserted into the chain, consisting of m carbon atoms and at least one heteroatom located between any two carbon atoms, for example, 1 to 3 heteroatoms selected from S, O, and N. The nitrogen and sulfur atoms are optionally oxidized, and the nitrogen atom is optionally quaternized. The heteroatom or heteroatom group can be located at any position within the heterohydrocarbyl group, such as where the hydrocarbyl group is bonded to the rest of the molecule. Exemplary heteroalkyl groups include alkyl ethers, secondary and tertiary alkylamines, amides, alkyl sulfides, etc., and include alkoxy groups, alkylthio groups, and alkylamino groups. Unless otherwise specified, C 1~6 Heteroalkyl groups include C1, C2, C3, C4, C5, and C6 heteroalkyl groups, for example, C 1~6 Alkoxy group, C 1~6 Alkylthio group, C 1~6 It is an alkylamino group.

[0183] The term "heteroalkylene group" refers to a divalent functional group formed by removing one hydrogen atom from any position within a heteroalkyl group.

[0184] The term "alkoxy group" refers to an -O-alkyl group.

[0185] The term "alkenyl group" refers to an unsaturated aliphatic hydrocarbon group consisting of carbon atoms and hydrogen atoms, either in a straight or branched chain, having at least one double bond. Non-exclusive examples of alkenyl groups include, but are not limited to, ethenyl, 1-propenyl, 2-propenyl, 1-butenyl, isobutenyl, and 1,3-butadienyl groups.

[0186] The term "cycloalkenyl group" refers to a non-aromatic carbocyclic ring that is not fully saturated and can exist as a monocyclic, bicyclic bridging ring, or spirocyclic ring. Unless otherwise specified, such carbocyclic rings are generally 4-16 membered, 4-12 membered, 4-10 membered, or 4-8 membered rings. Non-exclusive examples of cycloalkenyl groups include, but are not limited to, cyclopentenyl, cyclopentadienyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, and cycloheptadienyl groups.

[0187] The term "cycloalkyl group" refers to a carbon ring that is fully saturated and can exist as a monocycle, a crosslinked ring, or a spirocycle. Unless otherwise specified, such carbon rings are generally 3- to 16-membered rings, e.g., 3- to 10-membered rings, or 5- to 8-membered rings. Non-exclusive examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl (bicyclo[2.2.1]heptyl), bicyclo[2.2.2]octyl, and adamantanyl groups.

[0188] The term "heterocycloalkyl group" refers to a cyclic functional group that is fully saturated and can exist as a monocycle, a bridging ring, or a spirocycle. Unless otherwise specified, the heterocycle is generally a 3-16 membered ring, 3-11 membered ring, 3-10 membered ring, 3-7 membered ring, 3-6 membered ring, or 3-5 membered ring containing 1-3, preferably 1 or 2, heteroatoms independently selected from sulfur, oxygen, and / or nitrogen. Examples of 3-membered heterocycloalkyl groups include, but are not limited to, oxyranyl, thyranyl, and azilidinyl groups. Non-limiting examples of 4-membered heterocycloalkyl groups include, but are not limited to, azetidinyl, oxetanyl, and thietanyl groups. Examples of 5-membered heterocycloalkyl groups include, but are not limited to, tetrahydrofuryl, tetrahydrothienyl, pyrrolidinyl, isoxazolidinyl, oxazolidinyl, isothiazolidinyl, thiazolidinyl, imidazolidinyl, and tetrahydropyrazolyl groups. Examples of 6-membered heterocycloalkyl groups include, but are not limited to, piperidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, morpholinyl, piperazinyl, 1,4-thiooxanyl, 1,4-dioxanyl, thiomorpholinyl, 1,3-dithianyl, and 1,4-dithianyl groups. Examples of 7-membered heterocycloalkyl groups include, but are not limited to, azepanyl, oxepanyl, and thiepanyl groups. Monocyclic heterocycloalkyl groups having 5 or 6 ring atoms are preferred.

[0189] The term "spiro ring" refers to a fully saturated or partially unsaturated polycyclic system in which carbon atoms called spiro atoms are shared between monocyclic rings, and includes carbocyclic and heterocyclic rings. Unless otherwise specified, the spiro ring has 5 to 20 members, preferably 6 to 14 members, and more preferably 8 to 12 members. When the spiro ring is a heterocyclic ring, one or more ring atoms in the polycyclic ring are N, O, S(O) n , P(O) n (n is a heteroatom selected from 0, 1, or 2), preferably one or two heteroatoms, and the remaining ring atom is a carbon atom.

[0190] The term "spiroalkyl group" refers to a fully saturated polycyclic group of all carbon atoms in which carbon atoms called spiro atoms are shared between monocyclic rings. Unless otherwise specified, the spiroalkyl groups have 5 to 20 members, preferably 6 to 14 members, and more preferably 8 to 12 members. Depending on the number of spiro atoms shared between the rings, spiroalkyl groups are classified as monospiroalkyl groups, bisspiroalkyl groups, or multispiroalkyl groups. Preferably, they are monospiroalkyl groups and bisspiroalkyl groups, and more preferably 4-member / 4-member, 4-member / 5-member, 4-member / 6-member, 5-member / 5-member, or 5-member / 6-member monospiroalkyl groups. Non-limiting examples of spiroalkyl groups are: [ka] and [ka] Includes.

[0191] The term "spiroheterocycloalkyl group" refers to a fully saturated polycyclic ring in which carbon atoms called spiro atoms are shared between monocyclic rings, and one or more ring atoms in the polycyclic ring are N, O, S(O) n , P(O) n The spiroheterocycloalkyl group is a heteroatom selected from (n is 0, 1, or 2), preferably one or two heteroatoms, with the remaining ring atoms being carbon atoms. Unless otherwise specified, the spiroheterocycloalkyl group is 5 to 20 members, preferably 6 to 14 members, and more preferably 6 to 10 members. Depending on the number of spiroatoms shared between the rings, the spiroheterocycle is classified as a monospiroheterocycle, bisspiroheterocycle, or multispiroheterocycle, preferably a monospiroheterocycle or bisspiroheterocycle, and more preferably a 4-member / 4-member, 4-member / 5-member, 4-member / 6-member, 5-member / 5-member, or 5-member / 6-member monospiroheterocycle. Non-limiting examples of spiroheterocycloalkyl groups are: [ka] or [ka] This includes, among others.

[0192] The term "heterocycloalkenyl group" includes cycloalkenyl groups in which one or more carbon atoms, for example, 1 to 5, 1 to 4, 1 to 3, or 1 to 2, are substituted by heteroatoms. Specifically, for example, a cycloalkenyl group in which up to 3 carbon atoms, up to 2 carbon atoms in one embodiment, or 1 carbon atom in another embodiment, are independently substituted by O, S, S(O), or N, provided that at least one cycloalkenyl carbon-carbon double bond is retained. A cyclic functional group that can exist as a monoring, bridging ring, or spiroring, and which is a 3 to 16-membered ring, for example, a 3 to 12-membered ring, a 5 to 8-membered ring, specifically a 5-membered, 6-membered, 7-membered, 8-membered, 9-membered, 10-membered, or 11-membered ring. Examples of heterocycloalkenyl groups include, but are not limited to, dihydropyrrolyl, tetrahydropyridinyl, tetrahydroazepinyl, or azaspirooctene.

[0193] The term "aryl group" refers to an aromatic cyclic group that is either monocyclic or polycyclic and has a conjugated π-electron system. For example, an aryl group can have 6 to 20 carbon atoms, 6 to 14 carbon atoms, or 6 to 12 carbon atoms. Non-exclusive examples of aryl groups include, but are not limited to, the phenyl group, naphthyl group, anthryl group, and 1,2,3,4-tetrahydronaphthalene.

[0194] The term "heteroaryl group" refers to a monocyclic or fused polycyclic ring system containing at least one ring atom selected from N, O, and S, for example, 1 to 5, 1 to 4, 1 to 3, or 1 to 2 ring atoms, with the remaining ring atoms being carbon, and having at least one aromatic ring. Preferably, the heteroaryl group has one 4 to 8-membered ring, particularly a 5 to 8-membered ring, for example, a 5-membered ring, a 6-membered ring, a 7-membered ring, or an 8-membered ring, or multiple fused rings containing 6 to 14, particularly 6 to 10, ring atoms, for example, 6, 7, 8, 9, or 10 ring atoms. Non-exclusive examples of heteroaryl groups include, but are not limited to, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, quinolinyl, isoquinolinyl, tetrazolyl, triazolyl, triazinyl, benzofuryl, benzothienyl, indolyl, and isoindolyl groups.

[0195] Unless otherwise specified, the term "hetero" refers to a heteroatom or heteroatom group, i.e., a functional group containing a heteroatom, and includes atoms other than carbon (C) and hydrogen (H) and functional groups containing these heteroatoms, for example, oxygen (O), nitrogen (N), sulfur (S), phosphorus (P), silicon (Si), germanium (Ge), aluminum (Al), boron (B), - Includes O-, -S-, =O, =S, -P(=O)-, -P(=O)2-, -P(=O)O-, -P(=O)2O-, -C(=O)O-, -C(=O)-, -C(=S)-, -S(=O)-, -S(=O)2-, and -C(=O)N(H)-, -N(H)-, -C(=NH)-, -S(=O)2N(H)- or -S(=O)N(H)- which can be optionally substituted.

[0196] The term "derivative" refers to one or more new compounds produced through one or more chemical reactions or structural changes, in which the basic structure of the parent compound is retained, and only the side chains, functional groups, or substituents are altered or modified.

[0197] In the terms “substituent,” “optionally substituted by one or more substituents,” or “optionally substituted,” substitution or substitution by substituents includes all substituents referred to in the context of this specification, for example, “halogen,” “deuterium,” and “substitutable by substituents.” [ka] "-NH2" "-NH(C 1~4 Alkyl) -N(C 1~4 Alkyl)2" -OH" -OC 1~4 Alkyl alkyl group, -CN, C 1~4The terms "alkyl group" and "3-6 member heterocycloalkyl group" may also be used, and the corresponding non-limiting or exemplary functional groups may also be used. Some non-limiting examples of the "substituents" include mercapto group, nitro group, nitroso group, cyano group, azide group, sulfoxide group, sulfone group, sulfonamide group, carboxyl group, aldehyde group, imine group, alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, haloalkenyl group, cycloalkenyl group, halocycloalkenyl group, alkynyl group, haloalkynyl group, cycloalkynyl group, halocycloalkynyl group, heteroalkyl group, haloheteroalkyl group This includes groups such as alkoxy groups, alkylthio groups, aryl groups, aryloxy groups, arylthio groups, arylalkylene groups, arylalkoxy groups, arylalkylthio groups, heteroaryl groups, heteroaryloxy groups, heteroarylthio groups, heteroarylalkylene groups, heteroarylalkoxy groups, heteroarylalkylthio groups, heterocyclyl groups, heterocyclyloxy groups, heterocyclylthio groups, heterocyclylalkylene groups, heterocyclylalkoxy groups, heterocyclylalkylthio groups, acyl groups, acyloxy groups, carbamate groups, amide groups, ureido groups, epoxy groups, ester groups, and oxo groups.The substituents can be optionally oxo, hydroxyl, amino, nitro, halogen, cyano, alkyl, alkenyl, alkynyl, alkoxy, haloalkoxy, alkylamino, dialkylamino, haloalkylamino, halodialkylamino, carboxyl, -C(O)O-alkyl, -OC(O)-alkyl, -C(O)NH2, -C(O)NH-alkyl, -C(O)N(alkyl)2, -NHC(O)-alkyl, -C(O)-alkyl, -S(O)-alkyl, -S(O)2-alkyl Substituted with one or more substituents selected from -S(O)2NH2, -S(O)2NH-alkyl group, -S(O)2N(alkyl)2, cycloalkyl group, cycloalkylalkylene group, cycloalkyloxy, heterocyclyl group, heterocyclylalkylene group, heterocyclyloxy group, heterocycloalkyl group, heterocycloalkyloxy, heteroaryl group, heteroarylalkylene group, heteroaryloxy group, aryl group, arylalkylene group, or aryloxy group.

[0198] In some embodiments of this specification, the substituents are deuterium, tritium, hydroxyl group, mercapto group, halogen, amino group, nitro group, nitroso group, cyano group, azide group, sulfoxide group, sulfone group, sulfonamide group, carboxyl group, aldehyde group, imine group, C 1~12 Alkyl, halo C 1~12 Alkyl, 3-12 membered cycloalkyl, halo 3-12 membered cycloalkyl, C 2~12 Alkenyl group, Halo C 2~12 Alkenyl group, 3-12 membered cycloalkenyl group, halo 3-12 membered cycloalkenyl group, C 2~12 Alkynyl group, Halo C 2~12 Alkynyl group, 8-12 membered cycloalkynyl group, halo 8-12 membered cycloalkynyl group, C 1~12 Heteroalkyl groups, halo C 1~12 Heteroalkyl groups, C 1~12 Alkoxy group, C 1~12Alkylthio group, 6-10 membered aryl group, 6-10 membered aryloxy group, 6-10 membered arylthio group, 6-10 membered aryl C 1~12 Alkylene group, 6-10 membered aryl C 1~12 Alkoxy group, 6-10 membered aryl C 1~12 Alkylthio group, 5-10 member heteroaryl group, 5-10 member heteroaryloxy group, 5-10 member heteroarylthio group, 5-10 member heteroarylalkylene group, 5-10 member heteroarylalkoxy group, 5-10 member heteroarylalkylthio group, 3-12 member heterocyclyl group, 3-12 member heterocyclyloxy group, 3-12 member heterocyclylthio group, 3-12 member heterocyclyl C 1~12 Alkylene group, 3-12 member heterocycline C 1~12 Alkoxy group, 3-12 membered heterocyclyl C 1~12 Alkylthio group, C 1~12 Acyl group, C 1~12 Acyloxy group, carbamate group, C 1~12 Amide group, ureido group, epoxy group, C 2~12 The substituent is selected from ester groups and oxo groups. The substituent can be optionally oxo, hydroxyl, amino, nitro, halogen, cyano, or C 1~12 Alkyl alkyl group, C 2~12 Alkenyl group, C 2~12 Alkynyl group, C 1~12 Alkoxy group, Halo C 1~12 Alkoxy group, C 1~12 Alkylamino group, diC 1~12 alkylamino group, halo C 1~12 Alkylamino group, halo C 1~12 Alkylamino group, carboxyl group, -C(O)OC 1~12 Alkyl alkyl group, -OC(O)-C 1~12 Alkyl alkyl groups, -C(O)NH2, -C(O)NH-C 1~12 Alkyl group, -C(O)N(C 1~12 Alkyl)2,-NHC(O)-C 1~12 Alkyl alkyl group, -C(O)-C 1~12 Alkyl group, -S(O)-C 1~12 Alkyl group, -S(O)2-C 1~12Alkyl alkyl group, -S(O)2NH2, -S(O)2NH-C 1~12 Alkyl group, -S(O)2N(C 1~12 Alkyl) 2, 3-12 member cycloalkyl, 3-12 member cycloalkyl C 1~12 Alkylene group, 3-12 member cycloalkyloxy, 3-12 member heterocyclyl group, 3-12 member heterocyclyl C 1~12 Alkylene group, 3-12 member heterocyclyloxy group, 3-12 member heterocycloalkyl group, 3-12 member heterocycloalkyl C 1~12 Alkylene group, 3-12 member heterocycloalkyloxy, 5-10 member heteroaryl group, 5-10 member heteroaryl C 1~12 Alkylene group, 5-10 member heteroaryloxy group, 6-10 member aryl group, 6-10 member aryl C 1~12 It is substituted with one or more substituents selected from alkylene groups or 6-10 membered aryloxy groups.

[0199] Unless otherwise specified, the term "hetero" refers to a heteroatom or heteroatom group, i.e., a functional group containing a heteroatom, and includes atoms other than carbon (C) and hydrogen (H) and functional groups containing these heteroatoms, for example, heteroatoms include, but are not limited to, oxygen (O), nitrogen (N), sulfur (S), phosphorus (P), silicon (Si), germanium (Ge), aluminum (Al), and boron (B); specific Examples of heteroatoms or heteroatomic groups include -O-, -S-, -N=, =O, =S, -P(=O)-, -P(=O)2-, -P(=O)O-, -P(=O)2O-, -C(=O)O-, -C(=O)-, -C(=S)-, -S(=O), -S(=O)2-, and optionally substituted -C(=O)N(H)-, -N(H)-, -C(=NH)-, -S(=O)2N(H)- or -S(=O)N(H)-. Preferably, the heteroatom or heteroatomic group represented by the term "hetero," i.e., the heteroatom of a functional group containing a heteroatom, is selected from oxygen, nitrogen, or sulfur.

[0200] In this application, wavy line [ka] This represents one of the absolute configurations of the center of the solid (for example, [ka] or [ka] It is one of the following; specifically, [ka] teeth, [ka] or [ka] (represents) or one of the relative positions (for example, [ka] teeth, [ka] or [ka] (represented by...). If the compounds described herein contain alkene double bonds or other geometrically asymmetric centers, unless otherwise specified, they include E and Z geometric isomers. Similarly, all tautomer forms are included within the scope of this application.

[0201] In this application, -LNK 1 -Cy 1 -LNK-Cy 2 -LNK 2 -, -Cy 1 -Cy 2 -LNK 2 -, LNK, Cy 1 Cy 2 ,-Cy 1 -LNK-Cy 2 -, -Cy 1-LNK- or -LNK-Cy 2 - and other specific options, such as functional groups or structural fragments, can be read from left to right at will, and correspondingly, they are linked to the functional group on the left and the functional group on the right in the general formula. For example, L is -Cy 1 Selected from -LNK-, Cy 1 but [ka] When selected from, Reading from left to right, Cy 1 The left side is the corresponding left-hand fragment in the general formula. [ka] It is connected to the right side, and the right side is the right fragment [ka] The fragments formed in this way are connected to each other. [ka] That is the case. Optionally, -LNK in this application 1 -Cy 1 -LNK-Cy 2 -LNK 2 -, -Cy 1 -Cy 2 -LNK 2 -, LNK, Cy 1 Cy 2 ,-Cy 1 -LNK-Cy 2 -, -Cy 1 -LNK- or -LNK-Cy 2 - And the functional groups or structural fragments, such as specific options, can also be read from right to left, and correspondingly, they are linked to the functional group on the left and the functional group on the right in the general formula. For example, L is -Cy 1 Selected from -LNK-, Cy 1 but [ka] When selected from, Reading from right to left, Cy 1 The right side is the corresponding left-hand fragment in the general formula. [ka] It is linked to the right-hand fragment in the general formula, with the left side being the corresponding right-hand fragment. [ka] The fragments formed in this way are connected to each other. [ka] That is the case. The same applies to the other functional groups as described above.

[0202] The term "treatment" means administering the compounds or formulations described herein to improve or resolve a disease or one or more symptoms associated with the disease, and includes (i) suppressing the disease or disease state, i.e., inhibiting its progression; and (ii) alleviating the disease or disease state, i.e., resolving the disease or disease state.

[0203] The term "prevention" means administering the compounds or formulations described herein to prevent a disease or one or more symptoms associated with said disease. This includes preventing the onset of a disease or disease state in a mammal, particularly when such a mammal susceptible to the disease state has not yet been diagnosed with the disease state.

[0204] The term “therapeutic dose” means the amount of the Compound used that (i) treats or prevents a particular disease, condition or disorder; (ii) reduces, improves or eliminates one or more symptoms of a particular disease, condition or disorder; or (iii) prevents or delays the onset of one or more symptoms of a particular disease, condition or disorder as described herein. The “therapeutic dose” of the Compound will vary depending on the Compound, the state and severity of the disease, the method of administration, and the age of the treated mammal, but can be determined by a person skilled in the art based on their knowledge and the content of this disclosure.

[0205] The term "pharmaceutically acceptable" is used for compounds, materials, compositions and / or dosage forms that are suitable for use in contact with human and animal tissues, are non-toxic or irritating, do not cause allergic reactions or other problems or complications, and have a reasonable benefit-to-risk balance.

[0206] Examples of pharmaceutically acceptable salts include metal salts, ammonium salts, salts formed with organic bases, salts formed with inorganic acids, salts formed with organic acids, and salts formed with basic or acidic amino acids.

[0207] The term "pharmaceutical composition" refers to a mixture consisting of one or more of the compounds of the present invention or their salts and pharmaceutically acceptable additives. The pharmaceutical composition is intended to facilitate the administration of the compounds of the present invention to living organisms.

[0208] The term "pharmaceutically acceptable additive" refers to an additive that does not cause obvious irritation to living organisms and does not impair the physiological activity and properties of active compounds. For example, carbohydrates, waxes, water-soluble and / or water-swellable polymers, hydrophilic or hydrophobic materials, gelatin, oils, solvents, and water are well known to those skilled in the art as suitable additives.

[0209] The term "comprise" and similar terms, such as the English expressions "comprises" or "comprising," are understood in an open and non-exclusive sense, meaning "including, but not limited to, ...".

[0210] In this specification, unless otherwise explicitly stated in the context, singular terms cover multiple referents, and vice versa. Similarly, in this specification, unless otherwise explicitly stated in the context, the term “or” is intended to include the case of “and.”

[0211] In this specification, unless otherwise specified, any numbers used to express the amount of a component, a measured value, or reaction conditions are understood to be modified in all contexts by the term “approximately.” When used in conjunction with a percentage, the term “approximately” may mean, for example, ±1%, preferably ±0.5%, and more preferably ±0.1%.

[0212] The compounds and intermediates of this invention may also exist in different tautomer forms, and all such forms are included within the scope of this invention. The terms “tautomer” or “tautomer form” refer to structural isomers with different energies that can be interconverted by a low-energy barrier. For example, proton tautomers (also called prototropic tautomers) include interconversion by proton transfer, e.g., ketone-enol isomerization, imine-enamine isomerization. A specific example of a proton tautomer is an imidazole moiety in which a proton can be transferred between two ring nitrogen atoms. Specifically, for example, any compound of this disclosure that is pyrazole alone or part of a heterocyclyl group may exist in the form of any one tautomer or any mixture of any number of two tautomers, as described below. [ka] , or [ka] This disclosure includes all possible tautomers of the compounds relating to this disclosure, a single tautomer, or any mixture of such tautomers in any proportion.

[0213] The present application further includes the same compounds as those described herein, except in which one or more atoms are substituted with atoms whose atomic weight or mass number differs from that of ordinary atoms or mass numbers found in nature, i.e., isotope-labeled compounds. Examples of isotopes that can be bonded to the compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, iodine, and chlorine, for example, each of which 2 H, 3 H, 11 C, 13 C, 14 C, 13 N, 15 N, 15 O, 17 O, 18 O, 31 P, 32 P, 35 S, 18 F, 123 I, 125 I and 36 Examples include Cl.

[0214] The compound of this invention labeled with several isotopes, for example, 3 H, 14 Labeled with C can be used for tissue distribution analysis of compounds and / or substrates. Tritification, i.e., 3 H, carbon-14, that is, 14 C is particularly preferred because it is easy to manufacture and detect. Positron-emitting isotopes, for example, 15 O, 13 N, 11 C, 18 F can be used to measure substrate occupancy in positron emission tomography (PET) studies. Generally, isotope-labeled compounds of the present invention can be prepared by replacing an isotope-labeled reagent with an isotope-labeled reagent using a procedure similar to the embodiments and / or examples disclosed below.

[0215] Also, isotopes with large mass numbers, for example, deuterium, i.e.2 Substitution with hydrogen (H) is preferable in some cases because it provides greater metabolic stability and therapeutic benefits, such as an extended in vivo half-life or a reduction in the required dose. However, deuterium substitution may be partial or complete, and partial deuterium substitution refers to the substitution of at least one hydrogen atom with at least one deuterium atom.

[0216] The compounds of this invention may be asymmetric, for example, having one or more stereoisomers. Unless otherwise specified, this includes all stereoisomers, such as enantiomers and diastereomers. Compounds of this invention containing an asymmetric carbon atom can be separated into an optically pure form or a racemic form. The optically pure form can be separated from a racemic mixture or synthesized using chiral starting materials or chiral reagents.

[0217] The pharmaceutical compositions of this application can be manufactured by combining the compound of this application with appropriate pharmaceutically acceptable additives. For example, they can be manufactured as solid, semi-solid, liquid, or gaseous preparations such as tablets, pills, capsules, powders, granules, creams, emulsions, suspensions, suppositories, injections, inhalants, gels, microspheres, and aerosols.

[0218] Typical routes of administration of the compound of the present application or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof include, but are not limited to, oral, rectal, topical, inhalation, parenteral, sublingual, vaginal, nasal, intraocular, intraperitoneal, intramuscular, subcutaneous, and intravenous.

[0219] The pharmaceutical composition of this application can be manufactured by conventional methods known in the art, such as mixing, dissolving, granulation, sugar coating, grinding, emulsifying, and freeze-drying.

[0220] In some embodiments, the pharmaceutical composition is in a form for oral administration. For oral administration, the pharmaceutical composition can be prepared by mixing the active compound with pharmaceutically acceptable additives well known in the art. These additives allow the compound to be formulated as tablets, pills, sugar-coated tablets, capsules, liquids, gels, syrups, suspensions, etc., for oral administration to patients.

[0221] Oral solid compositions can be manufactured by conventional methods such as mixing, filling, and tableting. For example, they can be obtained by mixing the active compound with a solid additive and optionally grinding the mixture. If necessary, other suitable additives can be added, and the mixture can then be processed to obtain granules to obtain the core of a tablet or sugar-coated tablet. Suitable additives include, but are not limited to, binders, diluents, disintegrants, lubricants, flow enhancers, sweeteners, and flavoring agents.

[0222] The pharmaceutical composition is also suitable for parenteral administration, such as sterile solutions, suspensions, or lyophilized products in appropriate unit doses.

[0223] In all administration methods of compounds of general formula I described herein, the daily dose is 0.01 to 200 mg / kg body weight, and the dose is administered as a single dose or in several divided doses.

[0224] The compounds of this application can be produced by various synthetic methods familiar to those skilled in the art. These methods include the specific embodiments listed below, embodiments combined with other chemical synthesis methods, and equivalent alternative forms familiar to those skilled in the art, and preferred embodiments include, but are not limited to, the examples of this application.

[0225] The chemical reactions of the specific embodiments of this application are carried out in a suitable solvent, which must be compatible with the chemical changes and the reagents and raw materials used. In some cases, it may be necessary for those skilled in the art to modify or select synthesis steps or reaction processes based on conventional embodiments in order to obtain the compounds of this application.

[0226] In this field, one of the important factors to consider when planning synthetic routes is the selection of reactive functional groups, such as the appropriate protecting group for the amino group in this application. For more information on this, see, for example, "Greene's Protective Groups in Organic Synthesis (4th Ed). Hoboken, New Jersey: John Wiley & Sons, Inc."

[0227] In some embodiments, L is -Cy 1 When it is -LNK-, the compound of formula I-2 of this application can be produced by an engineer in the field of organic synthesis using the following intermediate or salt thereof via the following route. [ka] In the formula, ring A, ring B, ring C, ring F, R 1 , n, R 2 , m, R 3 , p, R 4 q, X 5 , X 6 Cy 1 The definition of LNK is as described herein; R x This is selected from leaving groups, for example, halogens (fluorine, chlorine, bromine, or iodine); R p This is selected from protecting groups, for example, Boc.

[0228] The following abbreviations are used in this application. DMSO represents dimethyl sulfoxide; DMF represents N,N-dimethylformamide; MeOH represents methanol; IBX represents 2-iodoxybenzoic acid; DIPEA represents N,N'-diisopropylethylamine; HATU represents 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate; DCE represents dichloroethane; iPrOH represents isopropanol; Boc represents tert-butoxycarbonyl group; DC 50Dmax represents the drug concentration at which the degradation rate reaches 50%; Dmax represents the maximum degradation rate.

[0229] The present invention will be further explained below using examples to clarify its nature. However, the scope of this application is not limited to the examples. All reagents used in this application are commercially available and can be used without purification. [Modes for carrying out the invention]

[0230] Example 1: Synthesis of Compound 1 [ka] Step 1: Preparation of intermediate 1b Intermediate 1a (10 g), 4-piperidine methanol (8.97 g), DMSO (100 mL), and DIPEA (16.77 g) were added in that order to a necked flask, and the mixture was heated to 90°C to react. Once the reaction was complete, the reaction mixture was cooled to room temperature, and ethyl acetate and water were added to the system for extraction. The organic phase was separated, and the aqueous phase was further extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, the solvent was removed by vacuum distillation, and the mixture was purified by silica gel column chromatography to obtain intermediate 1b (10.03 g). MS(ESI,[M+H] + )m / z:250.2

[0231] Step 2: Preparation of intermediate 1c Intermediate 1b (2.7g), MeOH (40mL), water (5mL), and sodium hydroxide (1.24g) were added in this order to a necked flask, and the mixture was heated to 50°C to react. Once the reaction was complete, the reaction solution was cooled to room temperature, 3N dilute hydrochloric acid was added to the system to adjust the pH to weakly acidic, the solvent was removed by vacuum distillation, and methanol was added to the concentrate to dissolve the product. The mixture was filtered, the filtrate was collected, and the solvent was removed from the filtrate by vacuum distillation to obtain intermediate 1c (1.82g). MS(ESI,[MH] - )m / z:234.1

[0232] Step 3: Preparation of intermediate 1d Intermediate 1c (235 mg), intermediate 2d (175 mg), DMF (5 mL), DIPEA (0.562 mL), and HATU (321 mg) were added in this order to a necked flask, and the mixture was reacted at room temperature. Once the reaction was complete, ethyl acetate and water were added to the system for extraction. The organic phase was separated, the aqueous phase was extracted with ethyl acetate, the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, the solvent was removed by vacuum distillation, and the mixture was purified by silica gel column chromatography to obtain intermediate 1d (0.22 g). MS(ESI,[M+H] + )m / z:492.1

[0233] Step 4: Preparation of intermediate 1e Intermediate 1d (220 mg), DMSO (2 mL), and IBX (405 mg) were added in that order to a necked flask, and the mixture was reacted at room temperature. Once the reaction was complete, ethyl acetate and saturated sodium bicarbonate aqueous solution were added to the system and extracted. The organic phase was separated, and the aqueous phase was further extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by vacuum distillation to obtain intermediate 1e (190 mg).

[0234] Step 5: Preparation of Compound 1 Intermediate 1e (200 mg), intermediate z1 (131 mg) (see Example 19 of WO2023088406 for the synthesis route), DCE:iPrOH = 5:1 (5 mL), sodium acetate (35.4 mg), and sodium triacetoxyborohydride (268 mg) were added in this order to a necked flask, and the mixture was reacted at room temperature. Once the reaction was complete, the solvent was removed by vacuum distillation, and the mixture was purified by silica gel column chromatography to obtain compound 1 (128 mg). MS(ESI,[M+H] + )m / z:759.6. 1H NMR(500MHz,DMSO-d6)δ 11.08(s,1H),7.74(d,J=8.5Hz,2H),7.64(d,J=8.6Hz,1H),7.58(d,J=8.1Hz,1H),7.48(d,J=9.2Hz,1H),7.11(d,J=8.3H) z,1H),6.96(d,J=8.6Hz,2H),6.64(d,J=2.2Hz,1H),6.54(dd,J=8.6,2.2Hz,1H),4.56(dd,J=11.9,5.0Hz,1H),4.27(s,1 H),4.05(d,J=9.1Hz,1H),3.91(s,5H),3.71(s,2H),3.00(t,J=5.6Hz,2H),2.85-2.72(m,5H),2.61(dt,J=17.3,4.3Hz,1 H),2.49-2.44(m,1H),2.40(d,J=7.1Hz,2H),2.19(dq,J=13.8,4.8Hz,1H),1.95-1.79(m,3H),1.22(s,8H),1.15(s,6H).

[0235] Example 2: Synthesis of Compound 2 [ka] Step 1: Preparation of intermediate 2c Intermediate 2a (6g) and DMF (30mL) were added to the reaction flask in that order, sodium hydride (1.479g) was added under ice bath, and the mixture was stirred under ice bath for 20 minutes. Intermediate 2b (4.47g) was then added, and the mixture was allowed to react at room temperature. Once the reaction was complete, the reaction solution was slowly poured into 300mL of ice water to quench the reaction, filtered to obtain a cake, and the cake was dried to obtain intermediate 2c (8.9g). MS(ESI,[M+H] + )m / z:275.42. 1 H NMR(500MHz,DMSO-d6)δ 7.62(d,J=8.6Hz,1H),6.65(d,J=9.5Hz,1H),6.60(d,J=2.2Hz,1H),6.50(dd,J=8.7,2. 3Hz,1H),4.12(s,1H),3.93(s,1H),3.89(s,3H),1.40(s,9H),1.13(s,6H),1.06(s,6H).

[0236] Step 2: Preparation of intermediate 2d Intermediate 2c (8.9 g) and hydrochloric acid-dioxane solution (59.4 mL) were added in that order to a necked flask, and the mixture was allowed to react at room temperature. Once the reaction was complete, the solvent was removed by vacuum distillation, and the mixture was dried under vacuum to obtain intermediate 2d (8.2 g). MS(ESI,[M+H] + )m / z:275.21. 1 H NMR(500MHz,DMSO-d6)δ 8.47(d,J=6.3Hz,3H),7.64(d,J=8.6Hz,1H),6.63(d,J=2.3Hz,1H),6.53(dd,J=8.7,2 .3Hz,1H),4.31(s,1H),3.90(s,3H),3.06(q,J=6.0Hz,1H),1.32(s,6H),1.11(s,6H).

[0237] Step 3: Preparation of 2g of intermediate Intermediate 2e (2g), intermediate 2f (1.782g), DMF (20mL), and potassium carbonate (5.35g) were added in this order to a necked flask, and the mixture was heated to 110°C to react. Once the reaction was complete, the reaction solution was cooled to room temperature, and ethyl acetate and water were added to the system for extraction. The organic phase was separated, and the aqueous phase was further extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, the solvent was removed by vacuum distillation, and the mixture was purified by silica gel column chromatography to obtain intermediate 2g (0.72g). MS(ESI,[M+H] + )m / z:251.0. 1 H NMR(500MHz,DMSO-d6)δ 8.36(d,J=3.0Hz,1H),7.84(d,J=8.9Hz,1H),7.31(dd,J=8.9,3.1Hz,1H),4.49(t,J=5.3Hz,1H),4.02-3.95(m,2H),3 .79(s,3H),3.30-3.24(m,2H),2.86(td,J=12.7,2.8Hz,2H),1.81-1.71(m,2H),1.69-1.56(m,1H),1.25-1.12(m,2H).

[0238] Step 4: Preparation of intermediate 2h Referring to the preparation procedure for intermediate 1c in Step 2 of Example 1, intermediate 1b was replaced with 2g of intermediate and the reaction was carried out to obtain intermediate 2h (0.86g). MS(ESI,[M+H] + )m / z:237.23. 1 H NMR(500MHz,DMSO-d6)δ 8.30(d,J=3.0Hz,1H),8.03(d,J=9.1Hz,1H),7.75(dd,J=9.2,2.9Hz,1H),4.06(dt,J=13.4,3.4Hz,2H),3.28(d,J=6. 2Hz,2H), 3.00(td,J=12.6,2.6Hz,2H),1.83-1.73(m,2H),1.68(tq,J=11.4,3.5Hz,1H),1.21(qd,J=12.5,4.1Hz,2H).

[0239] Step 5: Preparation of intermediate 2i Referring to the preparation procedure for intermediate 1d in step 3 of Example 1, intermediate 1c was replaced with intermediate 2h and the reaction was carried out to obtain intermediate 2i (0.25 g). MS(ESI,[M+H] + )m / z:493.44. 1 H NMR(500MHz,DMSO-d6)δ 8.33(d,J=2.9Hz,1H),8.09(d,J=9.1Hz,1H),7.82(d,J=8.8Hz,1H),7.64(d,J=8.6Hz,1H),7.41(dd,J=8 .9,2.9Hz,1H),6.67(d,J=2.2Hz,1H),6.57(dd,J=8.7,2.2Hz,1H),4.49(t,J=5.3Hz,1H),4.37(s,1H),3. 99-3.93(m,3H),3.91(s,3H),3.28(t,J=5.7Hz,2H),2.85(td,J=12.6,2.7Hz,2H),2.69(s,1H),1.74(dd, J=13.7,3.6Hz,2H),1.62(dtd,J=14.1,7.7,3.4Hz,1H),1.23(d,J=8.7Hz,1H),1.20(s,6H),1.15(s,6H).

[0240] Step 6: Preparation of intermediate 2j Referring to the preparation procedure for intermediate 1e in step 4 of Example 1, intermediate 1d was replaced with intermediate 2i and the reaction was carried out to obtain intermediate 2j (210 mg). MS(ESI,[M+H] + )m / z:491.25

[0241] Step 7: Preparation of Compound 2 Referring to the preparation procedure for compound 1 in step 5 of Example 1, intermediate 1e was replaced with intermediate 2j and the reaction was carried out to obtain compound 2 (160 mg). MS(ESI,[M+H] + )m / z:760.01. 1 H NMR(500MHz,DMSO-d6)δ 11.08(s,1H),8.34(d,J=3.0Hz,1H),8.09(d,J=9.1Hz,1H),7.83(d,J=8.8Hz,1H),7.64(d,J=8.6Hz,1H),7.58(d,J=8.2Hz,1H),7.42(dd,J=9.0 ,2.9Hz,1H),7.11(d,J=8.3Hz,1H),6.67(d,J=2.2Hz,1H),6.57(dd,J=8.6,2.2Hz,1H),4.56(dd,J=11.9,5.0Hz,1H),4.37(s,1H),3.95(dd,J=10 .7,5.0Hz,3H),3.91(s,3H),3.71(s,2H),3.00(t,J=5.7Hz,2H),2.94-2 .85(m,2H),2.82-2.73(m,3H),2.61(dt,J=17.2,4.2Hz,1H),2.47(dd,J =12.1,4.4Hz,1H),2.40(d,J=7.1Hz,2H),2.19(dq,J=13.4,4.6Hz,1H),1.94(d,J=7.0Hz,1H),1.84(d,J=13.0Hz,2H),1.20(s,8H),1.15(s,6H).

[0242] Example 3: Synthesis of Compound 3 [ka] Step 1: Preparation of intermediate 3b Referring to the procedure for preparing 2g of intermediate in Step 3 of Example 2, intermediate 2e was replaced with intermediate 3a to prepare intermediate 3b (2.5g). MS(ESI,[M+H] + )m / z:251.31. 1 H NMR(500MHz,DMSO-d6)δ 8.62(d,J=2.3Hz,1H),7.90(dd,J=9.0,2.5Hz,1H),6.85(d,J=9.1Hz,1H),4.51-4.40(m,3H),3.78(s,3H),3 .27(t,J=5.7Hz,2H),2.90(td,J=12.8,2.6Hz,2H),1.77-1.62(m,3H),1.09(tdd,J=12.7,11.2,4.3Hz,2H).

[0243] Step 2: Preparation of intermediate 3c Referring to the preparation procedure for intermediate 1c in Step 2 of Example 1, intermediate 1b was replaced with intermediate 3b and the reaction was carried out to obtain intermediate 3c (0.86 g). MS(ESI,[M+H] + )m / z:237.31. 1 H NMR(500MHz,DMSO-d6)δ 8.41(d,J=2.3Hz,1H),8.11(dd,J=9.6,2.3Hz,1H),7.31(d,J=9.6Hz,1H),4.44(d,J=13. 4Hz,2H),3.28(d,J=5.9Hz,2H),3.24-3.17(m,2H),1.86-1.71(m,3H),1.30-1.16(m,2H).

[0244] Step 3: Preparation of intermediate 3d Referring to the preparation procedure for intermediate 1d in step 3 of Example 1, intermediate 1c was replaced with intermediate 3c and the reaction was carried out to obtain intermediate 3d (0.25 g). MS(ESI,[M+H] + )m / z:493.45. 1H NMR(500MHz,DMSO-d6)δ 8.61(d,J=2.5Hz,1H),7.93(dd,J=9.0,2.6Hz,1H),7.64(d,J=8.6Hz,1H),7.58(d,J=9.3 Hz,1H),6.85(d,J=9.0Hz,1H),6.64(d,J=2.2Hz,1H),6.54(dd,J=8.6,2.3Hz,1H),4.50-4 .39(m,3H),4.25(s,1H),4.05(d,J=9.2Hz,1H),3.91(s,3H),3.27(t,J=5.7Hz,2H),2.87 (td,J=12.8,2.6Hz,2H),1.77-1.62(m,3H),1.22(s,6H),1.14(s,6H),1.12-1.07(m,2H).

[0245] Step 4: Preparation of intermediate 3e Referring to the preparation procedure for intermediate 1e in step 4 of Example 1, intermediate 1d was replaced with intermediate 3d and the reaction was carried out to obtain intermediate 3e (210 mg). MS(ESI,[M+H] + )m / z:491.27.

[0246] Step 5: Preparation of Compound 3 Referring to the preparation procedure for compound 1 in step 5 of Example 1, intermediate 1e was replaced with intermediate 3e and the reaction was carried out to obtain compound 3 (150 mg). MS(ESI,[M+H] + )m / z:759.90. 1H NMR(500MHz,DMSO-d6)δ 11.08(s,1H),8.62(d,J=2.5Hz,1H),7.93(dd,J=9.0,2.5Hz,1H),7.64(d,J=8.5Hz,1H),7.58(d,J=8.6Hz,2H),7.11(d,J=8.3Hz,1H),6.85(d,J= 9.1Hz,1H),6.64(d,J=2.2Hz,1H),6.54(dd,J=8.7,2.2Hz,1H),4.56(dd,J=11.9,5.0Hz,1H),4.42(d,J=13.0Hz,2H),4.25(s,1H),4.05(d,J=9.1H) z,1H),3.91(s,3H),3.71(s,2H),3.00(t,J=5.8Hz,2H),2.93(td,J=13. 1,2.6Hz,2H),2.82-2.72(m,3H),2.61(dt,J=17.3,4.3Hz,1H),2.47(dd, J=12.2,4.4Hz,1H),2.38(d,J=7.1Hz,2H),2.19(dq,J=13.6,4.8Hz,1H), 1.99(t,J=3.8Hz,1H),1.83(d,J=12.8Hz,2H),1.22(s,6H),1.14(s,8H).

[0247] Example 4: Synthesis of Compound 4 [ka] Step 1: Preparation of intermediate 4b Referring to the preparation procedure for 2g of intermediate in Step 3 of Example 2, intermediate 2e was replaced with intermediate 4a to prepare intermediate 4b (6.8g). MS(ESI,[M+H] + )m / z:266.2.

[0248] Step 2: Preparation of intermediate 4c Referring to the preparation procedure for intermediate 1c in Step 2 of Example 1, intermediate 1b was replaced with intermediate 4b and the reaction was carried out to obtain intermediate 4c (1.54 g). MS(ESI,[MH] - )m / z:236.1.

[0249] Step 3: Preparation of intermediate 4d Referring to the preparation procedure for intermediate 1d in step 3 of Example 1, intermediate 1c was replaced with intermediate 4c and the reaction was carried out to obtain intermediate 4d (0.26 g). MS(ESI,[M+H] + )m / z:494.1.

[0250] Step 4: Preparation of intermediate 4e Referring to the preparation procedure for intermediate 1e in step 4 of Example 1, intermediate 1d was replaced with intermediate 4d and the reaction was carried out to obtain intermediate 4e (224 mg).

[0251] Step 5: Preparation of Compound 4 Referring to the preparation procedure for compound 1 in step 5 of Example 1, intermediate 1e was replaced with intermediate 4e and the reaction was carried out to obtain compound 4 (142 mg). MS(ESI,[M+H] + )m / z:760.9. 1 H NMR(500MHz,DMSO-d6)δ 11.07(s,1H),8.75(s,2H),7.70(d,J=9.2Hz,1H),7.64(d,J=8.6Hz,1H),7.58(d,J=8.2Hz,1H),7.11(d,J=8.3Hz,1H),6.64(d ,J=2.3Hz,1H),6.54(dd,J=8.6,2.2Hz,1H),4.75(d,J=13.0Hz,2H),4.56(dd,J=11.9,5.0Hz,1H),4.23(s,1H),4.03(d,J=9.2H) z,1H),3.91(s,3H),3.71(s,2H),2.99(d,J=11.1Hz,4H),2.77(tt,J=11.8,5.9Hz,3H),2.61(dt,J=17.3,4.3Hz,1H),2.53(s, 1H),2.49-2.43(m,1H),2.39(d,J=7.2Hz,2H),2.19(dq,J=13.5,4.9Hz,1H),1.85(d,J=12.1Hz,2H),1.22(s,6H),1.13(s,8H).

[0252] Example 5: Synthesis of Compound 5 [ka] Step 1: Preparation of intermediate 5b Referring to the preparation procedure for intermediate 1d in step 3 of Example 1, intermediate 1c was replaced with intermediate 5a and the reaction was carried out to obtain intermediate 5b (0.56 g). MS(ESI,[M+H] + )m / z:415.4.

[0253] Step 2: Preparation of intermediate 5c Intermediate 5b (0.56 g), intermediate 2f (0.3 g), acetonitrile (20 mL), and potassium carbonate (0.55 g) were added in this order to a necked flask, and the mixture was heated to 80°C and reacted. Once the reaction was complete, ethyl acetate and water were added to the system for extraction. The organic phase was separated, and the aqueous phase was further extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, the solvent was removed by vacuum distillation, and the mixture was purified by silica gel column chromatography to obtain intermediate 5c (0.48 g). MS(ESI,[M+H] + )m / z:494.1.

[0254] Step 3: Preparation of intermediate 5d Referring to the preparation procedure for intermediate 1e in step 4 of Example 1, intermediate 1d was replaced with intermediate 5c and the reaction was carried out to obtain intermediate 5d (425 mg).

[0255] Step 4: Preparation of Compound 5 Referring to the preparation procedure for compound 1 in step 5 of Example 1, intermediate 1e was replaced with intermediate 5d and the reaction was carried out to obtain compound 5 (98 mg). MS(ESI,[M+H] + )m / z:761.0. 1H NMR(500MHz,DMSO-d6)δ 11.08(s,1H),8.61(d,J=1.2Hz,1H),8.33(d,J=1.5Hz,1H),7.81(d,J=9.1Hz,1H),7.64(d,J=8.6Hz,1H),7.58(d,J=8.2Hz,1H),7 .11(d,J=8.2Hz,1H),6.66(d,J=2.3Hz,1H),6.56(dd,J=8.7,2.3Hz,1H),4.56(dd,J=11.9,5.0Hz,1H),4.49(d,J=13.2Hz,2H),4.3 7(s,1H),3.98-3.89(m,4H),3.72(s,2H),3.08-2.97(m,4H),2.76(dt,J=16.9,5.5Hz,3H),2.61(dt,J=17.3,4.4Hz,1H),2.47(dd, J=12.2,4.3Hz,1H),2.40(d,J=7.1Hz,2H),2.24-2.15(m,1H),2.08-1.97(m,1H),1.86(d,J=12.6Hz,2H),1.17(d,J=26.2Hz,14H).

[0256] Example 6: Synthesis of Compound 6 [ka] Step 1: Preparation of intermediate 6b Referring to the preparation procedure for intermediate 1b in Step 1 of Example 1, intermediate 1a was replaced with intermediate 6a and the reaction was carried out to obtain intermediate 6b (6.8g). MS(ESI,[M+H] + )m / z:252.0.

[0257] Step 2: Preparation of intermediate 6c Referring to the preparation procedure for intermediate 1c in Step 2 of Example 1, intermediate 1b was replaced with intermediate 6b and the reaction was carried out to obtain intermediate 6c (2.62 g). MS(ESI,[MH] - )m / z:236.1.

[0258] Step 3: Preparation of intermediate 6d Referring to the preparation procedure for intermediate 1d in step 3 of Example 1, intermediate 1c was replaced with intermediate 6c and the reaction was carried out to obtain intermediate 6d (0.17 g). MS(ESI,[M+H] + )m / z:494.1.

[0259] Step 4: Preparation of intermediate 6e Referring to the preparation procedure for intermediate 1e in step 4 of Example 1, intermediate 1d was replaced with intermediate 6d and the reaction was carried out to obtain intermediate 6e (162 mg).

[0260] Step 5: Preparation of Compound 6 Referring to the preparation procedure for compound 1 in step 5 of Example 1, intermediate 1e was replaced with intermediate 6e and the reaction was carried out to obtain compound 6 (78 mg). MS(ESI,[M+H] + )m / z:761.6. 1 H NMR(500MHz,DMSO-d6)δ 11.08(s,1H),8.24(d,J=9.2Hz,1H),7.82(d,J=9.5Hz,1H),7.64(d,J=8.6Hz,1H),7.58(d,J=8.1Hz,1H),7.37(d,J=9.7Hz,1H), 7.11(d,J=8.3Hz,1H),6.67(d,J=2.2Hz,1H),6.57(dd,J=8.6,2.2Hz,1H),4.60-4.47(m,3H),4.40(s,1H),4.00(d,J=9.2Hz,1H), 3.91(s,3H),3.72(s,2H),3.11-2.97(m,4H),2.77(dt,J=17.3,5.5Hz,3H),2.61(dt,J=17.2,4.2Hz,1H),2.54(d,J=4.6Hz,1H),2 .47(dd,J=12.1,4.2Hz,1H),2.40(d,J=7.2Hz,2H),2.19(dq,J=8.6,4.5Hz,1H),1.87(d,J=12.1Hz,2H),1.20(d,J=34.9Hz,14H).

[0261] Example 7: Synthesis of Compound 7 [ka] Step 1: Preparation of intermediate 7a Intermediate 2d (0.20 g), 7a-1 (0.19 g), DIPEA (0.33 g), and DMF (5 mL) were mixed, HATU (0.29 g) was added, and the mixture was allowed to react completely at room temperature. The reaction mixture was poured into water, extracted with ethyl acetate, and purified by silica gel column chromatography to obtain intermediate 7a (0.28 g). MS(ESI)m / z [M+H] + :563.31.

[0262] Step 2: Preparation of intermediate 7b Intermediate 7a (0.28 g), DCM (10 mL), and 4 M hydrochloric acid-dioxane solution (5 mL) were mixed and allowed to react completely at room temperature. The mixture was concentrated to obtain intermediate 7b (0.19 g). MS(ESI)m / z [M+H] + :463.25.

[0263] Step 3: Preparation of Compound 7 Intermediate 7b (0.11 g), intermediate z5 (0.07 g) (refer to intermediate 26f in WO2024037616 for the synthesis route), sodium acetate (0.04 g), and DCE / IPA (v:v=5:1) (5 mL) were mixed, and sodium triacetoxyborohydride (0.10 g) was added, and the mixture was allowed to react completely at room temperature. The reaction mixture was concentrated and purified by silica gel column chromatography to obtain compound 7 (0.06 g). MS(ESI)m / z [M+H] + :745.43. 1H NMR(500MHz,DMSO)δ 11.08(s,1H),7.76(d,J=8.6Hz,2H),7.63(dd,J=15.6,8.3Hz,2H),7.52(d,J=9.2Hz,1H),7.28(d,J=8.1Hz,1H),6.99(d ,J=8.9Hz,2H),6.64(d,J=2.2Hz,1H),6.54(dd,J=8.7,2.2Hz,1H),4.57(ddd,J=11.9,5.0,1.8Hz,1H),4.27(s,1H),4.06 (d,J=9.2Hz,1H),3.91(s,3H),3.35(s,1H),3.30-3.17(m,6H),2.93(d,J=13.0Hz,2H),2.86(dd,J=16.0,5.2Hz,1H),2.7 7(ddd,J=17.2,11.9,5.4Hz,1H),2.66-2.54(m,5H),2.41(d,J=7.3Hz,2H),2.23-2.16(m,1H),1.23(s,6H),1.15(s,6H).

[0264] Referring to the synthesis method for intermediate 7b, the following intermediate was synthesized. [Table 1]

[0265] Example 8: Synthesis of Compound 8 [ka] Intermediate 1e (0.1 g), intermediate z2 (0.08 g) (see Example 1 of WO2024037616 for the synthesis route), sodium acetate (0.04 g), 1,2-dichloroethane (10 mL), and isopropanol (2 mL) were added in this order to the reaction flask and reacted for 10 minutes with stirring at room temperature. Then, sodium triacetoxyborohydride (0.1 g) was added and the mixture was reacted at room temperature for 1 hour. Once the reaction was complete, the reaction was quenched with saturated sodium bicarbonate solution, extracted with dichloromethane, washed with saturated brine, concentrated, and purified by silica gel column chromatography to obtain compound 8 (0.10 g). MS(ESI,[M+H] +)m / z:745.41. 1 H NMR(500MHz,DMSO)δ 11.09(s,1H),7.73(dd,J=14.9,8.3Hz,3H),7.64(d,J=8.6Hz,1H),7.49(d,J=9.2Hz,1H),7.31(d,J=8.2Hz,1H),6.97(d ,J=9.0Hz,2H),6.64(d,J=2.2Hz,1H),6.54(dd,J=8.7,2.2Hz,1H),4.60(dd,J=11.9,5.0Hz,1H),4.27(s,1H),4.16(s,2 H),4.09-4.03(m,3H),3.91(s,5H),2.80(dddd,J=29.4,17.1,12.2,3.9Hz,3H),2.69-2.58(m,3H),2.54(d,J=4.5Hz,1H ),2.20(dq,J=13.6,4.8Hz,1H),1.93-1.85(m,2H),1.81(d,J=3.8Hz,1H),1.31-1.24(m,2H),1.23(s,6H),1.15(s,6H).

[0266] Example 9: Synthesis of Compound 9 [ka] Referencing the method described in Example 8, intermediate z2 was replaced with intermediate z3 (see Example 3 of WO2024037616 for the synthesis route) to synthesize compound 9 (0.08 g). MS(ESI,[M+H] + )m / z:759.39. 1H NMR(500MHz,DMSO)δ 11.07(s,1H),7.74(d,J=8.6Hz,2H),7.64(d,J=8.6Hz,1H),7.59(d,J=8.1Hz,1H),7.48(d,J=9.2Hz,1H),7.15(d,J=8.2Hz,1H) ,7.00-6.93(m,2H),6.64(d,J=2.3Hz,1H),6.54(dd,J=8.7,2.2Hz,1H),4.56(dd,J=11.9,5.0Hz,1H),4.27(s,1H),4.05(d,J=9 .2Hz,1H),3.91(s,3H),3.86(d,J=12.9Hz,2H),3.81(s,2H),2.96(t,J=5.7Hz,2H),2.89-2.72(m,5H),2.60(dt,J=17.3,4.2Hz ,1H),2.48(d,J=4.3Hz,1H),2.44(d,J=6.9Hz,2H),2.19(dt,J=13.2,4.8Hz,1H),1.99-1.80(m,3H),1.22(s,8H),1.14(s,6H).

[0267] Example 10: Synthesis of Compound 10 [ka] Referencing the method described in Example 8, intermediate z2 was replaced with intermediate z4 (see Example 5 of WO2024037616 for the synthesis route) to synthesize compound 10 (0.07 g). MS(ESI,[M+H] + )m / z:773.42. 1H NMR(500MHz,DMSO)δ 11.07(s,1H),7.74(d,J=8.8Hz,2H),7.65(d,J=8.6Hz,1H),7.54(d,J=7.9Hz,1H),7.49(d,J=9.2Hz,1H),7.18(d,J=8.1Hz,1H ),7.01-6.94(m,2H),6.64(d,J=2.2Hz,1H),6.54(dd,J=8.6,2.2Hz,1H),4.54(dd,J=11.9,5.0Hz,1H),4.27(s,1H),4.05(d,J= 9.2Hz,1H),3.91(s,5H),3.20-3.13(m,2H),3.09-3.01(m,2H),2.85-2.73(m,3H),2.62(ddt,J=21.6,17.5,5.1Hz,5H),2.47( dd,J=12.3,4.4Hz,1H),2.34(d,J=6.8Hz,2H),2.18(dq,J=13.6,4.1Hz,1H),1.83(t,J=14.6Hz,3H),1.23(s,8H),1.15(s,6H).

[0268] The synthesis methods of compounds 7 and 8 are as follows, and the synthesis methods of the following compounds are as follows. Table 2-1 Table 2-2 Table 2-3 Table 2-4 Table 2-5 Table 2-6

[0269] Example 27: Synthesis of Compound 27

change

[0270] Example 28: Synthesis of Compound 28 [ka] Referring to the method described in Example 8, intermediate 1e was replaced with intermediate 3e, and intermediate z2 was replaced with intermediate z7 (see Example 75 of WO2024037616 for the synthesis route) to synthesize compound 28 (0.11 g). MS(ESI,[M+H] + )m / z:774.43. 1H NMR(500MHz,DMSO)δ 10.50(s,1H),8.63(d,J=2.5Hz,1H),8.05(s,1H),7.94(dd,J=9.0,2.5Hz,1H),7.64(d,J=8.6Hz,1H),7.58(d,J=9.3Hz,1H),7.2 9(d,J=7.8Hz,1H),7.06(d,J=8.0Hz,1H),6.86(d,J=9.0Hz,1H),6.64(d,J=2.2Hz,1H),6.54(dd,J=8.6,2.2Hz,1H),4.43(d,J=13 .0Hz,2H),4.25(s,1H),4.05(d,J=9.5Hz,1H),3.91(s,3H),3.82(t,J=6.7Hz,2H),3.12(d,J=6.1Hz,2H),3.03-2.88(m,4H),2.77 (t,J=6.6Hz,2H),2.69-2.56(m,4H),2.32(d,J=6.6Hz,2H),1.85(t,J=14.8Hz,3H),1.23(s,6H),1.14(s,6H),1.13-1.05(m,2H).

[0271] Compounds 29-36 were prepared by referring to Example 3 or Compound 14, or the synthesis procedures disclosed in the prior art. [Table 3]

[0272] Test Example 1: Degradation effect of compounds on AR in cells 1.1 Measurement of the degradation activity of VCaP cells against AR Measurements were performed using the HTRF Human Androgen Receptor Detection Kit (cisbio, 64ANDRPEG). A 4x supplemented lysate buffer was prepared using the Blocking reagent stock solution (100x) and the lysate buffer stock solution (4x). A 1x supplemented lysate buffer was prepared using the 4x supplemented lysate buffer and ddH2O. Premixed antibody solutions were prepared using the detection buffer, androgen receptor Eu cryptate antibody, and androgen receptor d2 antibody.

[0273] VCaP cells in good growth condition were obtained, washed with PBS, digested with trypsin, and digestion was stopped by adding phenol-free red DMEM complete medium containing 1% CSS-FBS. The cells were collected in a centrifuge tube, and the cell density was set to 5 × 10⁶. 5The solution was adjusted to cells / mL, inoculated at 100 μL per well in a 96-well plate, and incubated overnight in a cell culture incubator. The compound was then loaded using a nanopipette, and a 5-fold gradient dilution was performed to achieve a final compound concentration of 100 nM to 0.032 nM. This was done in parallel in two wells, with a control group provided. After continuing incubation in the cell culture incubator for 24 hours, the medium was aspirated, and 40 μL of 1× Supplemented Lysis Buffer was added per well to lyse the cells. After shaking at room temperature for 40 minutes, 16 μL of the cell lysate was added to a 384-well plate, and 4 μL of Premixed antibody solutions were added per well. The mixture was allowed to stand at 25°C for 2 hours. Fluorescence values ​​at 665 nm / 620 nm were measured using an Envision microplate reader, and dose-response curves were fitted using 4-parameter logistic regression. 50 And Dmax was calculated. The results are shown in Table 1. [Table 4]

[0274] The test results indicate that the compound of this application, for example, the example compound, has degrading activity against AR in VCaP cells.

[0275] 1.2 Measurement of the degradation activity of LNCaP(T878A) cells against AR Measurements were performed using the HTRF Human Androgen Receptor Detection Kit (cisbio, 64ANDRPEG). A 4x supplemented lysate buffer was prepared using the Blocking reagent stock solution (100x) and the lysate buffer stock solution (4x). A 1x supplemented lysate buffer was prepared using the 4x supplemented lysate buffer and ddH2O. Premixed antibody solutions were prepared using the detection buffer, androgen receptor Eu cryptate antibody, and androgen receptor d2 antibody.

[0276] LNCaP cells in good growth condition were obtained, washed with PBS, digested with trypsin, and digestion was stopped by adding phenol-free red 1640 complete medium containing 2% CSS-FBS. The cells were collected in a centrifuge tube, and the cell density was set to 1 × 10⁶. 6The solution was adjusted to cells / mL, inoculated at 100 μL per well in a 96-well plate, and incubated overnight in a cell culture incubator. The compound was then loaded using a nanopipette, and a 2x gradient dilution was performed to achieve a final compound concentration of 500 nM to 0.488 nM. This was done in parallel in two wells, with a control group provided. After continuing incubation in the cell culture incubator for 24 hours, the medium was aspirated, and 40 μL of 1× Supplemented Lysis buffer was added per well to lyse the cells. After shaking at room temperature for 40 minutes, 16 μL of the cell lysate was added to a 384-well plate, and 4 μL of Premixed antibody solutions were added per well. The mixture was allowed to stand at 25°C for 2 hours. Fluorescence values ​​at 665 nm / 620 nm were measured using an Envision microplate reader, and dose-response curves were fitted using 4-parameter logistic regression. 50 And Dmax was calculated. The test results are shown in Table 2. [Table 5]

[0277] The test results indicate that the compound of this application, for example, the example compound, has degrading activity against AR in LNCaP cells.

[0278] 1.3 Measurement of the degradation activity of MDA-PCA-2B (L702H / T878A) cells against AR Measurements were performed using the HTRF Human Androgen Receptor Detection Kit (cisbio, 64ANDRPEG). A 4x supplemented lysate buffer was prepared using the Blocking reagent stock solution (100x) and the lysate buffer stock solution (4x). A 1x supplemented lysate buffer was prepared using the 4x supplemented lysate buffer and ddH2O. Premixed antibody solutions were prepared using the detection buffer, androgen receptor Eu cryptate antibody, and androgen receptor d2 antibody.

[0279] Good-growing MDA-PCA-2B cells were obtained, washed with PBS, digested with trypsin, and digestion was stopped by adding MDA-PCA-2B complete medium. The cells were collected in a centrifuge tube, and the cell density was set to 1 × 10⁻⁶. 6The mixture was adjusted to cells / mL, inoculated at 100 μL per well in a 96-well plate, and incubated overnight in a cell culture incubator. The compound was then loaded using a nanopipette, and a 5-fold gradient dilution was performed to achieve a final compound concentration of 5000 nM to 1.6 nM. This was done in parallel in two wells, with a control group provided. After continuing incubation in the cell culture incubator for 24 hours, the medium was aspirated, and 40 μL of 1× Supplemented Lysis buffer was added per well to lyse the cells. After shaking at room temperature for 40 minutes, 16 μL of the cell lysate was added to a 384-well plate, and 4 μL of Premixed antibody solutions were added per well. The mixture was allowed to stand at 25°C for 2 hours. Fluorescence values ​​at 665 nm / 620 nm were measured using an Envision microplate reader, and dose-response curves were fitted using 4-parameter logistic regression. 50 And Dmax was calculated. The results are shown in Table 3. [Table 6]

[0280] The test results indicate that the compound of this application, for example, the example compound, has degrading activity against AR in MDA-PCA-2B cells.

[0281] Test Example 2: In vitro cell proliferation inhibitory activity 2.1 Measurement of Proliferative Inhibitory Activity Against VCaP Cells VCaP cells in good growth condition were obtained, washed with PBS, digested with trypsin, and digestion was stopped by adding phenol-free red DMEM complete medium containing 5% CSS-FBS. The cells were collected in a centrifuge tube, and the cell density was set to 1 × 10⁶. 5The compound was adjusted to cells / mL and inoculated at 100 μL per well in a 96-well plate. Simultaneously, the compound was loaded using a nanopipette, and a 2x gradient dilution was performed to achieve final concentrations of 1000 nM to 0.061 nM and 5000 nM to 0.305 nM. This was performed in parallel on two wells, with a control group provided. After continuing incubation in a cell culture incubator for 168 hours, 10 μL of the measurement reagent CCK-8 (manufactured by Dojin Chemical Laboratories) was added to each well, and incubated in a cell culture incubator for 7.0 hours. Absorbance at 450 nm was measured using a PerkinElmer Envision microplate reader, and dose-response curves were fitted using 4-parameter logistic regression. IC 50 The calculation was performed. The results are shown in Table 4. [Table 7]

[0282] The test results indicate that the compound of the present invention, for example, the example compound, has proliferation inhibitory activity against VCaP cells.

[0283] 2.2 Measurement of proliferation inhibitory activity against LNCaP(T878A) cells LNCaP cells in good growth condition were obtained, washed with PBS, digested with trypsin, and digestion was stopped by adding phenol-free red 1640 complete medium containing 2% CSS-FBS. The cells were collected in a centrifuge tube, and the cell density was set to 1 × 10⁶. 5The compound was adjusted to cells / mL and inoculated at 100 μL per well in a 96-well plate. Simultaneously, the compound was loaded using a nanopipette, and a 2x gradient dilution was performed to achieve final concentrations of 1000 nM to 0.061 nM and 5000 nM to 0.305 nM. This was performed in parallel on two wells, with a control group provided. After continuing incubation in a cell culture incubator for 168 hours, 10 μL of the measurement reagent CCK-8 (manufactured by Dojin Chemical Laboratories) was added to each well, and incubated in a cell culture incubator for 2.0 hours. Absorbance at 450 nm was measured using a PerkinElmer Envision microplate reader, and dose-response curves were fitted using 4-parameter logistic regression. IC 50 The calculation was performed. The test results are shown in Table 5. [Table 8]

[0284] The test results indicate that the compound of the present invention, for example, the example compound, has proliferation inhibitory activity against LNCaP cells.

[0285] 2.3 Measurement of proliferation inhibitory activity against 22RV1(H875Y / ARV7) cells 22RV1 cells in good growth condition were obtained, washed with PBS, digested with trypsin, and digestion was stopped by adding 1640 complete medium containing 5% FBS. The cells were collected in a centrifuge tube, and the cell density was set to 5 × 10⁶. 4The compound was adjusted to cells / mL and inoculated at 100 μL per well in a 96-well plate. Simultaneously, the compound was loaded using a nanopipette, and a 3-fold gradient dilution was performed to achieve a final compound concentration of 5000 nM to 2.286 nM. This was done in parallel with two wells, and a control was also included. After continuing incubation in a cell culture incubator for 168 hours, 50 μL of the measurement reagent CellTiter-Glo (Promega) was added to each well, incubated at room temperature for 10 minutes, and then transferred to a blank plate at 100 μL per well. Luminescence values ​​were measured using a PerkinElmer Envision multimode microplate reader, and dose-response curves were fitted using 4-parameter logistic regression. IC 50 The calculation was performed. The test results are shown in Table 6. [Table 9]

[0286] The test results indicate that the compound of this application, for example, the example compound, has proliferation inhibitory activity against 22RV1 cells.

[0287] 2.4 Measurement of proliferation inhibitory activity against MDA-PCA-2B (L702H / T878A) cells Good-growing MDA-PCA-2B cells were obtained, washed with PBS, digested with trypsin, and digestion was stopped by adding MDA-PCA-2B complete medium. The cells were collected in a centrifuge tube, and the cell density was set to 1 × 10⁻⁶. 5The compound was adjusted to cells / mL and inoculated at 100 μL per well in a 96-well plate. Simultaneously, the compound was loaded using a nanopipette, and a 3-fold gradient dilution was performed to achieve a final compound concentration of 5000 nM to 2.286 nM. This was carried out in parallel on two wells, with a control group provided. After continuing incubation in a cell culture incubator for 168 hours, 10 μL of the measurement reagent CCK-8 (manufactured by Dojin Chemical Laboratories) was added to each well, and incubated in a cell culture incubator for 5.0 hours. Absorbance at 450 nm was measured using a PerkinElmer Envision microplate reader, and dose-response curves were fitted using 4-parameter logistic regression. IC 50 The calculation was performed. The test results are shown in Table 7. [Table 10]

[0288] The test results indicate that the compound of the present invention, for example, the compound used in the example, has proliferation inhibitory activity against MDA-PCA-2B cells.

[0289] Test Example 3: In vitro stability in liver microsomes Liver microsome incubation samples were prepared by mixing PBS buffer (pH 7.4), liver microsome solution (0.5 mg / mL), the test compound, and NADPH+MgCl2 solution, and incubating at 37°C and 300 rpm for 1 hour. A 0-hour sample was prepared by mixing PBS buffer (pH 7.4), liver microsome solution (0.5 mg / mL), and the test compound. Acetonitrile solution containing an internal standard was added to the sample to precipitate the protein and prepare the supernatant, which was then diluted with a 1:1 (v:v) acetonitrile-water mixture in preparation for LC / MS / MS measurement. The results are shown in Tables 8 and 9. [Table 11] [Table 12]

[0290] The test results demonstrate that the compound in question is stable in vitro in liver microsomes (human, dog, rat, or mouse).

[0291] Test Example 4: Pharmacokinetics in Mice ICR mice weighing 18-22g were adapted for 3-5 days, then randomly divided into groups of 9 mice each. The intragastric administration group received the test compound solution at a dose of 10 mg / kg (20 mg / kg or 30 mg / kg), while the intravenous administration group received the test compound solution at a dose of 1 mg / kg.

[0292] In the intragastric administration group, blood samples were collected at 15 minutes, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 24 hours, and 48 hours after administration. In the intravenous injection group, blood samples were collected at 0.083 minutes, 15 minutes, 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 24 hours, and 48 hours after administration. Blood was collected from the orbit to prepare the test plasma samples.

[0293] 30 μL of test plasma and criterion samples were aspirated, and acetonitrile solution containing an internal standard was added to precipitate proteins and obtain the supernatant. For LC / MS / MS analysis, the samples were diluted with a 1:1 (v:v) acetonitrile-water mixture. A non-compartment model was used for fitting. The test results are shown in Table 10. [Table 13]

[0294] The test results showed that the compound in question exhibited good in vivo pharmacokinetic properties, such as AUC and C1. max , t 1 / 2 This indicates that it has parameters such as F. For example, in the case of intragastric administration of 10 mpk, the AUC is greater than 15000 ng·h / mL, and C max It is greater than 600 ng / mL, t 1 / 2 It was longer than 8 hours.

[0295] Study Example 5: Pharmacodynamic evaluation of DPTC-AR in a VCap human prostate cancer B-NDG mouse subcutaneous transplant tumor model. 5 × 10¹⁶ VCap human prostate cancer cells were implanted in the right axilla of male SPF-modified B-NDG mice (provided by Baiaosaitu (Beijing) Biotechnology Co., Ltd.) per mouse. 6 Individual subcutaneous injections were administered (1:1 mixed injection with Matrigel). The average tumor volume was approximately 250 mm². 3 The animals were divided into groups when they reached a certain stage of development. The day of group division was designated as day 0. From day 0, the drug was administered intragastricly once daily (1-10 mpk), while the control group was simultaneously administered a solvent (DMSO + PEG40). Tumor volume was measured 2-3 times per week, and the body weight of the mice was weighed and the data recorded. The general behavior of the mice was observed and recorded daily. After the experiment was completed, the tumors were excised, weighed, and photographed.

[0296] The measurement indicators and calculation formulas were as follows. Tumor volume is TV(mm 3 ) = 1 / 2 × (a × b 2 ) where a is the longest diameter of the tumor and b is the shortest diameter of the tumor.

[0297] Relative tumor volume is RTV = TV t / TV0 is the tumor volume on day 0, and TV t This represents the tumor volume at each measurement.

[0298] The relative tumor growth rate is T / C (%) = T RTV / C RTV It is ×100%. Here, T RTV This is the RTV of the treatment group, C RTV This is the solvent control group RTV.

[0299] The tumor growth inhibition rate is calculated as TGI (%) = (1 - TW / TW0) × 100%, where TW is the tumor weight in the treatment group and TW0 is the tumor weight in the solvent control group.

[0300] The percentage change in weight is WCR(%) = (Wtt The formula is -Wt0) / Wt0 × 100%. Here, Wt0 is the body weight of the mouse on day 0, and Wt t This represents the weight of the mouse at the time of each measurement.

[0301] The test results indicate that the compounds of the present invention exhibit good in vivo tumor inhibitory activity, possessing parameters such as TV, RTV, T / C (%), TGI (%), and WCR (%). For example, at a dose of 3 mpk, the relative tumor growth rate (T / C) was less than 40% and the tumor growth inhibition rate (TGI) was greater than 66% on day 23.

Claims

1. Compounds of formula I, their stereoisomers, or pharmaceutically acceptable salts thereof. 【Chemistry 1】 (In the formula, ring A does not exist, or C ５～１５ Selected from a cycloalkenyl group, a 5-15 member heterocycloalkenyl group, a phenyl group, or a 5-6 member heteroaryl group; Ring B is selected from a phenyl group or a 5-6 membered heteroaryl group; Ring C is selected from 5-6 membered heteroaryl groups; Each R １ is independently selected from halogen, -OH, -NH ２ , -CN, C １～１０ alkyl group, C １～１０ alkoxy group, or halo C １～１０ alkyl group, and the -OH, -NH ２ , C １～１０ alkyl group, C １～１０ alkoxy group, or halo C １～１０ alkyl group is optionally substituted by one or more substituents; n is selected from 0, 1, 2, or 3; L is selected from the linking groups; X ５ C(R) ｆ ) or selected from N, R ｆ C is substituted with H, halogen, deuterium, or one or more substituents of any choice. １～６ Selected from alkyl groups; X ６ is -O-, -NH-, or -N(C １～６ Selected from alkyl) and the aforementioned -NH- or -N(C １～６ The alkyl group is optionally substituted with one or more substituents; Each R ２ , each R ３ and each R ４ These are halogen, -OH, and -NH, respectively. ２ ,-CN,C １～１０ alkyl group, C １～１０ Alkoxy group, or halo C １～１０ Selected independently of alkyl groups, the -OH, -NH ２ , C １～１０ alkyl group, C １～１０ Alkoxy group, or halo C １～１０ The alkyl group is optionally substituted with one or more substituents; m, p, and q are each independently selected from 0, 1, 2, 3, 4, 5, or 6; Ring G is C ６～１０ Selected from aryl groups or 5- to 10-membered heteroaryl groups; Ring E is C ３～１０ Selected from cycloalkyl groups or 3- to 10-membered heterocycloalkyl groups; Ring F is C ６～１０ Selected from aryl groups or 5- to 10-membered heteroaryl groups; R ｔ is hydrogen, -OH, C １～６ alkyl group, C ３～１０ Selected from cycloalkyl groups or 3- to 10-membered heterocycloalkyl groups, the C １～６ alkyl group, C ３～１０ The cycloalkyl group or the 3- to 10-membered heterocycloalkyl group may be optionally substituted with one or more substituents.

2. Ring A does not exist, or C ５～１０ Selected from a cycloalkenyl group, a 5-10 membered heterocycloalkenyl group, a phenyl group, or a 5-6 membered heteroaryl group; Alternatively, ring A does not exist, or C ５～９ Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, a phenyl group, or a 5- to 6-membered heteroaryl group; Alternatively, ring A does not exist, or C ５～７ Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, a phenyl group, or a 5- to 6-membered heteroaryl group; Alternatively, ring A does not exist, or C ５～６ Selected from a cycloalkenyl group, a 5-10 membered heterocycloalkenyl group, a phenyl group, or a 5-6 membered heteroaryl group; Alternatively, ring A does not exist, or C ５～６ Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, a phenyl group, or a 5- to 6-membered heteroaryl group; Alternatively, ring A does not exist, or C ５～６ Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, a phenyl group, or a 5-membered heteroaryl group; Alternatively, ring A does not exist, or C ５～６ Selected from a cycloalkenyl group, a 5- to 9-membered heterocycloalkenyl group, a phenyl group, a pyrrolyl group, a pyrazolyl group, a furyl group, or an oxazolyl group; Alternatively, ring A does not exist, or C ５ Cycloalkenyl group, C ６ Selected from a cycloalkenyl group, a 5-membered heterocycloalkenyl group, a 6-membered heterocycloalkenyl group, a 7-membered heterocycloalkenyl group, an 8-membered heterocycloalkenyl group, a 9-membered heterocycloalkenyl group, a phenyl group, a pyrrolyl group, a pyrazolyl group, a furyl group, or an oxazolyl group; Alternatively, ring A is absent, or is selected from a cyclopentenyl group, a monocyclohexenyl group, a bicyclohexenyl group, a dihydropyrrolyl group, a tetrahydropyridinyl group, a tetrahydroazepinyl group, an azaspirooctenyl group, an azaspirononenyl group, a phenyl group, a pyrrolyl group, a pyrazolyl group, a furyl group, an oxazolyl group, or a dihydrooxazinyl group, and / or Ring B is selected from a phenyl group or a six-membered heteroaryl group. Alternatively, ring B is selected from phenyl groups; and / or, Ring C is selected from a 5-membered heteroaryl group. Alternatively, the compound according to claim 1, its stereoisomer, or a pharmaceutically acceptable salt thereof, wherein ring C is selected from an isoxazolyl group or a furyl group.

3. The following structural fragments 【Chemistry 2】 teeth, 【Transformation 3】 or 【Chemistry 4】 Selected from; or the following structural fragments 【Transformation 5】 teeth, 【Transformation 6】 or 【Transformation 7】 Selected from; or the following structural fragments 【Transformation 8】 teeth, 【Chemistry 9】 or 【Chemistry 10】 Selected from; or the following structural fragments 【Chemistry 11】 teeth, 【Chemistry 12】 or 【Chemistry 13】 Selected from; or the following structural fragments 【Chemistry 14】 teeth, 【Chemistry 15】 or 【Chemistry 16】 Selected from; or the following structural fragments 【Chemistry 17】 teeth, 【Chemistry 18】 or 【Chemistry 19】 A compound according to claim 1 or 2, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, selected from among.

4. Each R １ Halogen, -OH, -NH ２ ,-CN,C １～６ alkyl group, C １～６ Alkoxy group, or halo C １～６ Selected independently of alkyl groups, the -OH, -NH ２ , C １～６ alkyl group, C １～６ Alkoxy group, or halo C １～６ The alkyl group is optionally substituted with one or more substituents; Alternatively, each R １ Halogen, -OH, -NH ２ ,-CN,C １～４ alkyl group, C １～４ Alkoxy group, or halo C １～４ Selected independently of alkyl groups; Alternatively, each R １ Halogen, -OH, -NH ２ ,-CN,C １～３ alkyl group, C １～３ Alkoxy group, or halo C １～３ Selected independently of alkyl groups; Alternatively, each R １ Fluorine, chlorine, bromine, -OH, -NH ２ Alternatively, selected independently of CN; Alternatively, each R １ is independently selected from fluorine, chlorine, or bromine; Alternatively, each R １ is selected independently of fluorine; and / or, n is selected from 0, 1, or 2; Alternatively, n is selected from 0 or 1, and is a compound according to any one of claims 1 to 3, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

5. L is a C which is optionally substituted with one or more substituents. １～５０ Alkylene group, C ２～５０ Alkenylene group or C ２～５０ Selected from the alkynylene group, the C １～５０ Alkylene group, C ２～５０ Alkenylene group or C ２～５０ One or more -CH groups in the alkynylene group ２ - is optionally -O-, C ３～１５ Cycloalkyl groups, 3-15 member heterocycloalkyl groups, 4-15 member heterocycloalkenyl groups, C ６～１５ Aryl group, 5-15 membered heteroaryl group, -NH-, -N(C) １～６ Replaced by alkyl)- or -S-; Alternatively, L may be optionally substituted with one or more substituents. １～３０ Alkylene group, C ２～３０ Alkenylene group or C ２～３０ Selected from the alkynylene group, the C １～３０ Alkylene group, C ２～３０ Alkenylene group or C ２～３０ One or more -CH groups in the alkynylene group ２ - is optionally -O-, C ３～１２ Cycloalkyl groups, 3-12 member heterocycloalkyl groups, 4-12 member heterocycloalkenyl groups, C ６～１２ Aryl group, 5-12 membered heteroaryl group, -NH-, -N(C) １～６ Replaced by alkyl)- or -S-; Alternatively, L is optionally a C alkylene group, C alkenylene group or C alkynylene group substituted by one or more substituents, and one or more -CH- in the C alkylene group, C alkenylene group or C alkynylene group are optionally replaced by -O-, C cycloalkyl group, 3-11 member heterocycloalkyl group, 4-10 member heterocycloalkenyl group, C aryl group, 5-10 member heteroaryl group, -NH-, -N(C alkyl)- or -S-; １～２０ alkylene group, C ２～２０ alkenylene group or C ２～２０ alkynylene group selected from, and the C １～２０ alkylene group, C ２～２０ alkenylene group or C ２～２０ alkynylene group in one or more -CH ２ - is optionally replaced by -O-, C ３～１０ cycloalkyl group, 3-11 member heterocycloalkyl group, 4-10 member heterocycloalkenyl group, C ６～１０ aryl group, 5-10 member heteroaryl group, -NH-, -N(C １～６ alkyl)- or -S-; Alternatively, L may be optionally substituted with one or more substituents. １～１５ Alkylene group, C ２～１５ Alkenylene group or C ２～１５ Selected from the alkynylene group, the C １～１５ Alkylene group, C ２～１５ Alkenylene group or C ２～１５ One or more -CH groups in the alkynylene group ２ - is optionally -O-, C ３～９ Cycloalkyl groups, 3-11 member heterocycloalkyl groups, 4-8 member heterocycloalkenyl groups, C ６～８ Aryl group, 5-8 membered heteroaryl group, -NH-, -N(C) １～４ Replaced by alkyl)- or -S-; Alternatively, L may be optionally substituted with one or more substituents. １～１０ Alkylene group, C ２～１０ Alkenylene group or C ２～１０ Selected from the alkynylene group, the C １～１０ Alkylene group, C ２～１０ Alkenylene group or C ２～１０ One or more -CH groups in the alkynylene group ２ - is optionally -O-, C ３～９ Cycloalkyl groups, 3-11 member heterocycloalkyl groups, 4-6 member heterocycloalkenyl groups, C ６ Aryl group, 5-6 membered heteroaryl group, -NH-, -N(C) １～３ Replaced by alkyl)- or -S-; Alternatively, L may be optionally substituted with one or more substituents. １～６ Alkylene group, C ２～６ Alkenylene group or C ２～６ Selected from the alkynylene group, the C １～６ Alkylene group, C ２～６ Alkenylene group or C ２～６ One or more -CH groups in the alkynylene group ２ - is optionally -O-, C ３～９ Cycloalkyl groups, 3-11 member heterocycloalkyl groups, 4-6 member heterocycloalkenyl groups, C ６ Aryl group, 5-6 membered heteroaryl group, -NH-, -N(C) １～３ Replaced by alkyl)- or -S-; Alternatively, L may be optionally substituted with one or more substituents. １～４ Alkylene group, C ２～４ Alkenylene group or C ２～４ Selected from the alkynylene group, the C １～４ Alkylene group, C ２～４ Alkenylene group or C ２～４ One or more -CH groups in the alkynylene group, for example, one or two, one or three, etc. ２ - is optionally -O-, C ４～６ Cycloalkyl groups, 4-6 member heterocycloalkyl groups, 4-6 member heterocycloalkenyl groups, C ６ Aryl group, 5-6 membered heteroaryl group, -NH-, -N(C) １～３ Replaced by alkyl) or -S-; or L is C １～６ Selected alkylene group, the C １～６ One or more -CH groups in the alkylene group ２ - is optionally -O-, C ３～１０ Cycloalkyl groups, 4-11 member heterocycloalkyl groups, 4-10 member heterocycloalkenyl groups, -NH-, -N(C) １～３ Replaced by alkyl) or -S-, and the C １～６ The alkylene group may be optionally substituted with one or more substituents; Alternatively, L is C １～６ Selected alkylene group, the C １～６ One or more -CH groups in the alkylene group ２ - is optionally -O-, C ３～１０ Cycloalkyl groups, 4-11 member heterocycloalkyl groups, 5-6 member heterocycloalkenyl groups, -NH-, -N(C) １～３ Replaced by alkyl) or -S-, and the C １～６ The compound according to any one of claims 1 to 4, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the alkylene group is optionally substituted with one or more substituents.

6. L is -LNK １ -Cy １ -LNK-Cy ２ -LNK ２ -Cy ３ - Selected from, here, Cy １ Cy ２ or Cy ３ Each of these is a combination, or one or more Rs of any choice. ａ C is replaced by ３～１２ Independently selected from cycloalkyl groups, 4-12 member heterocycloalkyl groups, or 4-12 member heterocycloalkenyl groups; LNK, LNK １ and LNK ２ Each of these is a bond, NH, O, S, or optionally one or more R ｂ C is replaced by １～１２ Alkylene group, C ２～１２ Alkenylene group, C ２～１２ Alkynylene group or C １～１２ Independently selected from heteroalkylene groups; Each R ａ and each R ｂ These are halogen, =O, -OH, and -NH, respectively. ２ ,-CN,C １～６ alkyl group, C １～６ Alkoxy group, Halo C １～６ alkyl group, C １～６ Alkylamino group, diC １～６ Alkylamino group, C ３～１２ A compound according to any one of claims 1 to 4, independently selected from a cycloalkyl group or a 4- to 12-membered heterocycloalkyl group, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

7. LNK, LNK １ and LNK ２ Each of these is a bond, NH, O, S, or one or more Rs, respectively. ｂ C is replaced by １～１０ Alkylene group, C ２～１０ Alkenylene group, C ２～１０ Alkynylene group or C １～１０ Independently selected from heteroalkylene groups; Or, LNK, LNK １ and LNK ２ Each of these is a bond, NH, O, S, or one or more Rs, respectively. ｂ C is replaced by １～６ Alkylene group, C ２～６ Alkenylene group, C ２～６ Alkynylene group or C １～６ Independently selected from heteroalkylene groups; Or, LNK, LNK １ and LNK ２ Each of these is a bond, NH, O, S, or one or more Rs, respectively. ｂ C is replaced by １～４ Alkylene group, C ２～４ Alkenylene group, C ２～４ Alkynylene group or C １～４ Independently selected from heteroalkylene groups; Or, LNK, LNK １ and LNK ２ Each of these is a bond, NH, O, S, or one or more Rs, respectively. ｂ C is replaced by １～６ Alkylene group or C １～６ Independently selected from heteroalkylene groups; Or, LNK, LNK １ and LNK ２ Each of these is a bond, NH, O, S, or one or more Rs, respectively. ｂ C is replaced by １～４ Alkylene group or C １～４ Independently selected from heteroalkylene groups; Or, LNK, LNK １ and LNK ２ Each of these is a bond, NH, O, or optionally one or more R ｂ C is replaced by １～３ Alkylene group or C １～３ Independently selected from heteroalkylene groups; Or, LNK, LNK １ and LNK ２ Each of these is a bond, NH, O, or optionally one or more R ｂ C is replaced by １～２ Alkylene group or C １～２ Independently selected from heteroalkylene groups; Or, LNK, LNK １ and LNK ２ These are, respectively, bond, NH, O, and -NHCH. ２ -ien-CH ２ NHCH ２ -ien-CH ２ -ien-CH ２ CH ２ -, -C(O)- or -C(O)CH ２ - Selected independently of; and / or Cy １ Cy ２ Or Cy ３ Each of these can be combined, or one or more Rs can be selected arbitrarily. ａ C is replaced by ３～１１ Independently selected from cycloalkyl groups, 4-12 membered heterocycloalkyl groups, or 4-11 membered heterocycloalkenyl groups; Or, Cy １ Cy ２ Or Cy ３ Each of these can be combined, or one or more Rs can be selected arbitrarily. ａ C is replaced by ４～１０ Independently selected from cycloalkyl groups, 4-11 member heterocycloalkyl groups, or 5-6 member heterocycloalkenyl groups; Or, Cy １ Cy ２ Or Cy ３ Each of these can be combined, or one or more Rs can be selected arbitrarily. ａ C is replaced by ４～９ Independently selected from cycloalkyl groups, 4-11 member heterocycloalkyl groups, or 5-6 member heterocycloalkenyl groups; Or, Cy １ Cy ２ Or Cy ３ Each of these can be combined, or one or more Rs can be selected arbitrarily. ａ C is replaced by ４～６ Cycloalkyl groups, C ９ Independently selected from cycloalkyl groups, 4- to 11-membered heterocycloalkyl groups, or 6-membered heterocycloalkenyl groups; Or, Cy １ Cy ２ Or Cy ３ Each of these can be combined, or one or more Rs can be selected arbitrarily. ａ A compound according to claim 6, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, independently selected from a cyclobutyl group, cyclopentyl group, cyclohexyl group, spirononanyl group, azetidinyl group, pyrrolidinyl group, piperidinyl group, tetrahydropyridinyl group, piperazinyl group, monoazaspiroheptyl group, monoazaspironanyl group, diazaspirononanyl group, monoazaspirodecyl group, diazaspirodecyl group, monoazaspirowndecanyl group, diazaspironodecanyl group, octahydrocyclopentapyrrolyl group, diazabicyclooctyl group, or monoazabicyclononanyl group substituted by the above.

8. Each R ａ and each R ｂ These are halogen, =O, -OH, and -NH, respectively. ２ ,-CN,C １～６ alkyl group, C １～６ Alkoxy group, Halo C １～６ alkyl group, C １～６ Alkylamino group, diC １～６ Alkylamino group, C ３～１０ Independently selected from cycloalkyl groups or 4- to 10-membered heterocycloalkyl groups; Alternatively, each R ａ and each R ｂ These are halogen, =O, OH, and NH, respectively. ２ , CN, C １～６ alkyl group, C １～６ Alkoxy group, Halo C １～６ alkyl group, C １～６ Alkylamino group or diC １～６ Selected independently from alkylamino groups; Alternatively, each R ａ and each R ｂ These are halogen, =O, -OH, and -NH, respectively. ２ ,-CN,C １～４ alkyl group, C １～４ Alkoxy group, Halo C １～４ alkyl group, C １～４ Alkylamino group, or diC １～４ Selected independently from alkylamino groups; Alternatively, each R ａ and each R ｂ These are halogen, =O, -OH, and -NH, respectively. ２ , -CN or C １～３ Selected independently of alkyl groups; Alternatively, each R ａ and each R ｂ These are halogen, =O, -OH, and -NH, respectively. ２ Alternatively, selected independently of CN; Alternatively, each R ａ and each R ｂ Each of these is independently selected from =O, and is a compound according to claim 6 or 7, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

9. L is a bond, -NHCH ２ -ien-CH ２ NHCH ２ -ien-CH ２ -, -C(O)CH ２ - 【Chemistry 20-1】 【Chemistry 20-2】 or 【Chemistry 21】 A compound selected from any one of claims 1 to 8, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

10. R ｆ C is substituted with H, fluorine, chlorine, bromine, deuterium, or one or more substituents as optional. １～３ Selected from alkyl groups; Or, R ｆ is H, fluorine, chlorine, bromine, deuterium, or C １～３ Selected from alkyl groups, the C １～３ Alkyl groups can optionally consist of one or more halogens, -OH, and -NH. ２ Alternatively, it may be replaced by -CN; Or, R ｆ is H, fluorine, chlorine, bromine, deuterium, or C １～３ Selected from alkyl groups; Or, R ｆ is selected from H, fluorine, deuterium or methyl group, and / or X ５ is selected from CH or N; and / or X ６ is -O-, -NH-, or -N(C １～３ Selected from alkyl; or X ６ is -O- or -N(CH ３ ) - selected from; or X ６ is a compound selected from -O-, according to any one of claims 1 to 9, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

11. Each R ２ , each R ３ and each R ４ These are halogen, -OH, and -NH, respectively. ２ ,-CN,C １～６ alkyl group, C １～６ Alkoxy group, or halo C １～６ Selected independently of alkyl groups, the -OH, -NH ２ ,-CN,C １～６ alkyl group, C １～６ Alkoxy group, or halo C １～６ The alkyl group is optionally substituted with one or more substituents; Alternatively, each R ２ , each R ３ and each R ４ These are halogen, -OH, and -NH, respectively. ２ ,-CN,C １～４ alkyl group, C １～４ Alkoxy group, or halo C １～４ Selected independently of alkyl groups; Alternatively, each R ２ Halogen, -OH, -NH ２ ,-CN,C １～３ alkyl group, C １～３ Alkoxy group, or halo C １～３ Selected independently of alkyl groups; Alternatively, each R ２ Halogen, -OH, -NH ２ ,-CN,C １～３ Alkyl or C １～３ Selected independently of the alkoxy group; Alternatively, each R ２ Fluorine, chlorine, bromine, -OH, -NH ２ , independently selected from -CN, a methyl group or a methoxy group; Alternatively, each R ２ is independently selected from fluorine, chlorine, bromine, -CN, or methoxy groups; Alternatively, each R ２ is independently selected from -CN or methoxy groups; and / or Each R ３ These are halogen, -OH, and -NH, respectively. ２ ,-CN,C １～３ alkyl group, C １～３ Alkoxy group, or halo C １～３ Selected independently of alkyl groups; Alternatively, each R ３ These are halogen, -OH, and -NH, respectively. ２ , -CN or C １～３ Selected independently of alkyl groups; Alternatively, each R ３ These are C １～３ Selected independently of alkyl groups; Alternatively, each R ３ Each is independently selected from the methyl group; and / or Each R ４ These are halogen, -OH, and -NH, respectively. ２ ,-CN,C １～３ alkyl group, C １～３ Alkoxy group, or halo C １～３ Selected independently of alkyl groups; Alternatively, each R ４ These are halogen, -OH, and -NH, respectively. ２ , -CN or C １～３ Selected independently of alkyl groups; Alternatively, each R ４ These are fluorine, chlorine, bromine, -OH, and -NH, respectively. ２ Alternatively, a compound according to any one of claims 1 to 10, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, independently selected from -CN.

12. m is selected from 0, 1, 2 or 3; or m is selected from 1, 2 or 3; or m is selected from 2; and / or p is selected from 1, 2, 3 or 4; or p is selected from 3 or 4; or p is selected from 4; and / or A compound, stereoisomer thereof, or pharmaceutically acceptable salt thereof according to any one of claims 1 to 11, wherein q is selected from 0, 1, 2, or 3; or q is selected from 0 or 1; or q is selected from 0.

13. The compound according to any one of claims 1 to 12, its stereoisomer or a pharmaceutically acceptable salt thereof, wherein ring G is selected from a phenyl group or a 5- to 6-membered heteroaryl group; or ring G is a phenyl group.

14. Ring E is C ３～９ Selected from cycloalkyl groups or 3- to 9-membered heterocycloalkyl groups; or, ring E is C ４～９ Selected from cycloalkyl groups or 4- to 9-membered heterocycloalkyl groups; or, ring E is C ４～７ Selected from cycloalkyl groups or 4- to 7-membered heterocycloalkyl groups; or, ring E is C ４～７ Selected from cycloalkyl groups; Alternatively, ring E is selected from a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group; Alternatively, ring E is a cyclobutyl group; or, ring E is one of the following: 【Chemistry 22】 Alternatively, ring E is as follows: 【Chemistry 23】 A compound according to any one of claims 1 to 13, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

15. Ring F is C ６～１０ Ring F is selected from an aryl group or a 5- to 7-membered heteroaryl group; or Ring F is selected from a phenyl group or a 5- to 6-membered heteroaryl group; or Ring F is selected from a phenyl group or a 6-membered heteroaryl group; or Ring F is selected from a phenyl group, a pyridinyl group, a pyridadinyl group, a pyrimidinyl group or a pyrazinyl group; or Ring F is selected from a phenyl group; or Ring F is 【Chemistry 24】 or 【Chemistry 25】 A compound, stereoisomer thereof, or pharmaceutically acceptable salt thereof, selected from any one of claims 1 to 14.

16. R ｔ is hydrogen, -OH, C １～４ alkyl group, C ３～６ Selected from cycloalkyl groups or 3-6 member heterocycloalkyl groups, the C １～４ alkyl group, C ３～６ A cycloalkyl group or a 3- to 6-membered heterocycloalkyl group may be optionally substituted; or R ｔ is hydrogen, -OH, C １～３ alkyl group, C ３～４ Selected from cycloalkyl groups or 3-4 member heterocycloalkyl groups, the C １～３ alkyl group, C ３～４ A cycloalkyl group or a 3-4 member heterocycloalkyl group may be optionally substituted; or R ｔ is hydrogen or C １～３ Alkyl groups, for example, selected from methyl, ethyl, and propyl groups; or R ｔ is a compound according to any one of claims 1 to 15, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, selected from hydrogen.

17. The following structural fragments 【Chemistry 26】 teeth, 【Chemistry 27】 Selected from; or the following structural fragments 【Chemistry 28】 teeth, 【Chemistry 29】 Selected from; or the following structural fragments 【Transformation 30】 teeth, 【Chemistry 31】 Selected from; or the following structural fragments 【Chemistry 32】 teeth, 【Transformation 33】 Selected from; or the following structural fragments 【Transformation 34】 teeth, 【Chemistry 35】 Selected from; or the following structural fragments 【Transformation 36】 teeth, 【Chemistry 37】 Selected from; or the following structural fragments 【Chemistry 38】 teeth, 【Chemistry 39】 or 【Chemistry 40】 A compound according to any one of claims 1 to 16, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, selected from among.

18. The aforementioned compound, its stereoisomer, or pharmaceutically acceptable salt thereof is a compound of formula I-1 or formula I-1A, a compound of formula I-2, formula I-2A, formula I-3, or formula I-3A, its stereoisomer, or a pharmaceutically acceptable salt thereof. 【Chemistry 41】 or 【Chemistry 42】 X is selected from CH or N, and is a compound according to any one of claims 1 to 17, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

19. Ring A is C ５～１０ A cycloalkenyl group, or a 5-15 membered heterocycloalkenyl group containing 1-2 heteroatoms selected from N or O; ring B is a phenyl group; ring C is a 5-6 membered heteroaryl group containing 1-2 heteroatoms selected from N or O; n is 0; X ５ C(R) ｆ ) selected from R ｆ is H, deuterium, or C １～６ Selected from alkyl groups; L is C １～１０ It is an alkylene group, and the C １～１０ One or more -CH groups in the alkylene group ２ - is C, which is optional. ５～８ Replaced by a cycloalkyl group, or a 5-8 membered heterocycloalkyl group containing 1-3 or 1-2 N or O atoms, Each R ２ These are independently -OH and -NH ２ ,-CN,C １～１０ alkyl group, C １～１０ Alkoxy group, or halo C １～１０ It is an alkyl group; each R ３ These are independently halogen, C １～１０ Alkyl alkyl group, or halo C １～１０ It is an alkyl group; q is 0, m is 0, 1, 2 or 3, and p is 0, 1, 2, 3 or 4; X ６ is -O- or -NH-; ring G is a phenyl group or a six-membered heteroaryl group containing one or two N or O atoms; ring E is C ３～６ It is a cycloalkyl group; ring F is a phenyl group, or a six-membered heteroaryl group containing one to three or one to two N or O atoms; R ｔ is hydrogen, -OH, or C １～６ A compound according to any one of claims 1 to 18, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is an alkyl group.

20. Compounds, moieties, stereoisomers, derivatives, or pharmaceutically acceptable salts thereof of formula I' or formula I''. 【Chemistry 43】 (In the formula, ring A does not exist, or C ５～１０ Selected from a cycloalkenyl group, a 5-10 membered heterocycloalkenyl group, a phenyl group, or a 5-6 membered heteroaryl group; Ring B is selected from phenyl groups; Ring C is selected from an isoxazolyl group or a furyl group; L is selected from the linking group.

21. Compounds, moieties, stereoisomers, derivatives, or pharmaceutically acceptable salts thereof of formula I'-a or formula I''-a. 【Chemistry 44】 (In the formula, ring A does not exist, or C ５～１０ Selected from a cycloalkenyl group, a 5-10 membered heterocycloalkenyl group, a phenyl group, or a 5-6 membered heteroaryl group; Ring B is selected from phenyl groups; Ring C is selected from an isoxazolyl group or a furyl group; Each R １ａ Halogen, -OH, -NH ２ , -CN,=O, -CHO,C １～４ alkyl group, C １～４ Alkoxy group, C １～６ Alkyl OC(O)-, C ３～１２ A cycloalkyl group is independently selected from cycloalkyl groups or 4- to 12-membered heterocycloalkyl groups, and the C １～４ alkyl group, C １～４ Alkoxy group, C ３～１２ The cycloalkyl group or 4- to 12-membered heterocycloalkyl group can optionally contain one or more halogens, =O, -OH, -NH ２ , -CN, CHO, COOH, -C １～４ Alkyl-OH, C １～６ Alkyl OC(O)-, or optionally C １～６ Substituted by a 4- to 10-membered heterocycloalkyl group substituted with alkyl COC(O)-; n is selected from 0, 1, 2, or 3.

22. The aforementioned compound, 【Chemistry 45-1】 【Chemistry 45-2】 【Chemistry 45-3】 【Chemistry 45-4】 【Chemistry 45-5】 【Chemistry 45-6】 【Chemistry 45-7】 【Chemistry 45-8】 【Chemistry 45-9】 or 【Chemistry 46】 The compound according to any one of claims 1 to 19, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

23. A pharmaceutical composition comprising a compound according to any one of claims 1 to 19 and 22, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a compound, a portion thereof, a stereoisomer thereof, a derivative thereof, or a pharmaceutically acceptable salt thereof, according to claim 20 or 21.

24. Use of a compound according to any one of claims 1 to 19 and 22, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a compound according to claim 20 or 21, a portion thereof, a stereoisomer thereof, a derivative thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 23, in the manufacture of a drug for preventing or treating a disease condition treated by degrading a target protein bound to a targeted ligand.

25. The use of a compound according to any one of claims 1 to 19 and 22, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a compound according to claim 20 or 21, a portion thereof, a stereoisomer thereof, a derivative thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 23, in the manufacture of a drug for preventing or treating a medical condition treated by binding to cereblon protein in vivo.

26. The use according to claim 24 or 25, wherein the disease or condition is selected from cancer.

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