Compounds for methods of targeting protein degradation

Abstract

A compound of formula I or a salt, solvate or prodrug thereof: Q-L-M (I) wherein Q is a protein binding moiety of formula Q1 or formula Q2, L is a linker moiety; and M is an E3 ubiquitin ligase binding moiety. In addition, a pharmaceutical composition and combination comprising the compounds of formula I and the use of the compounds, compositions and combinations in therapy, in particular in the treatment or prevention of diseases or conditions mediated by RIPK1 kinase.

Description

[0001] introduction This invention relates to bifunctional compounds comprising a protein-binding moiety and an E3 ubiquitin ligase-binding moiety. The compounds disclosed herein can be used in methods for targeted protein degradation; in particular, the compounds disclosed herein are proteolytically targeted chimeric (PROTAC) protein degraders.

[0002] The protein-binding moiety binds to the protein of interest, while the E3 ubiquitin ligase-binding moiety recruits and binds to the E3 ubiquitin ligase. The compounds disclosed herein induce ubiquitination of the protein of interest and its subsequent degradation by the ubiquitin-proteasome system through simultaneous binding of the protein of interest and the ligase.

[0003] In one embodiment, the compounds disclosed herein target RIPK1 kinase and are therefore effective in treating or preventing diseases or conditions mediated by RIPK1 kinase. Background of the Invention Receptor-interacting protein kinase-1 (RIPK1) has emerged as a promising therapeutic target for treating a variety of human conditions, including cancer, neurodegeneration, and autoimmune disorders. 1-3 Recent studies have shown that RIPK1 plays a crucial role in determining cell death outcomes in response to various stimuli, including chemotherapy, radiation therapy, and immunotherapy. Furthermore, RIPK1 has been found to be involved in the development of cancer cell resistance to immunotherapy. 4 .

[0005] RIPK1 biology is complex because RIPK1 can positively and negatively regulate cell death and inflammation. 5,6 This depends on the environment. While controlled activation of RIPK1 contributes to tissue repair and immune surveillance, chronic dysregulated activation of RIPK1 signaling can lead to many immune diseases and autoinflammatory diseases. 7-12 Blocking RIPK1-induced cell death has been shown to rescue inflammation-driven symptoms in several disease models. 1-3 It has been found that proteins encoding negative regulators of RIPK1, such as... TBK1 , A20 (also known as) TNFAIP3 ), ABIN1 (also known as) TNIP1 ), NEMO , OTULIN and LUBAC Mutations in the genes of complex members and abnormal activation of RIPK1 trigger RIPK1-mediated autoimmune disorders and autoinflammatory conditions (in... 1(Reviewed in Chinese), the autoimmune disorders and autoinflammatory conditions mentioned include rheumatoid arthritis, psoriasis and dermatitis, as well as chronic neurodegenerative conditions such as multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer's disease. 2,13,14 Since these proteins negatively regulate RIPK1, mutational impairment or age-related decline in protein expression or function has been shown to drive chronic RIPK1 activation, which in turn leads to persistent cell death and inflammation. Consistently, targeting RIPK1 kinase activity in arthritis... 10,11 And inflammatory bowel disease (IBD) 15 In mouse models, symptoms induced by A20 deficiency were significantly suppressed. Similarly, as a result of chronic activation of RIPK1, symptoms in intestinal epithelial cells were significantly suppressed. Nemo The deficiency of RIPK1 leads to colitis. Similarly, dysregulated RIPK1 kinase-mediated cell death may be a potential mechanism leading to inflammatory diseases. 9 Therefore, RIPK1 dysregulation is a common feature in chronic inflammatory diseases, indicating RIPK1 as a promising therapeutic target.

[0006] Regarding cancer, using small molecules to target RIPK1 can overcome apoptosis resistance and trigger a more immunogenic form of cell death. 16,17 Such as necroptosis, has the potential to enhance the effectiveness of cancer therapies. Necrotosis is a form of lytic cell death that is often associated with pathogens and is therefore highly effective in evoking strong immune responses. 18,19 Furthermore, necroptosis can kill apoptotic resistant tumor cells. In addition, recent data suggest that cancer cells frequently hijack RIPK1 to promote resistance to immunotherapy by blocking immunogenic forms of cell death. 4 Importantly, the scaffold function of RIPK1 helps enhance cell survival and the production of immunosuppressive chemokine programs, ultimately leading to reduced CD8 and NK cell infiltration and significant resistance to ICB. 4 .

[0007] Although RIPK1 has become a major therapeutic target, its immunosuppressive and pro-survival activities cannot be neutralized by kinase inhibitors alone. This is because RIPK1's ability to promote cell survival and resistance to immunotherapy depends not only on its kinase function but also on its scaffold activity. Furthermore, while kinase inhibitors are highly effective in mice, they only partially inhibit RIPK1-induced cell death in humans because they do not block RIPK1-induced apoptosis in human cells. Therefore, alternative strategies that specifically target RIPK1 scaffold function, such as using PROTAC degraders, could be more effective in treating RIPK1-driven diseases.

[0008] There is a need in the art for alternative and / or improved compounds and alternative / improved methods for specifically targeting and degrading certain proteins such as RIPK1. For example, compounds with improved binding specificity to proteins such as RIPK1 and / or improved pharmacokinetic parameters such as plasma stability, bioavailability, and similar parameters are desirable in the art. Invention Overview In one aspect, the present invention provides a compound of formula I or a salt, solvate, or prodrug thereof: in Q is the formula Q 1 or Q 2 Protein-binding portion: (Q 1 ) (Q 2 ) in R 1 Choose the group consisting of the following items: C 3-11 cycloalkyl, C 3-11 cycloalkyl (C 1-3 )alkyl, 3- to 12-membered heterocyclic alkyl, 3- to 12-membered heterocyclic alkyl (C 1-3 )alkyl, 5- to 12-membered heteroaryl (C 1-6 )alkyl, C 1-10 Alkyl, C 2-10 alkenyl and C 2-10 Alkyne groups, wherein each is optionally surrounded by one or more R groups a1 replace; Each R a1 Choose independently the group consisting of: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -OC 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=O)R b1 -C(=O)NR d1 R e1 -NR d1 R e1 -NR d1 C(=O)R b1 -OR c1 -SRc1 -OC(=O)R b1 -S(=O)2R c1 and -S(=O)2NR d1 R e1 Wherein C 1-6 Alkyl, OC 1-6 Alkyl, C 3-6 cycloalkyl, -OC 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl and C 6-11 The aryl group may optionally be substituted by one or more groups selected from the following: hydroxyl, halogen, =O, -CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl, phenyl, -C(O)C 1-6 Alkyl, -C(O)N(H)C 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl group 2, -CONH2, -C(O)N(H)C 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl)2、-N(H)C 1-6 Alkyl and -N(C) 1-6 Alkyl)2; Where R b1 R c1 R d1 and R e1 Choose independently the group consisting of: hydrogen, hydroxyl, C 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 alkyl and phenyl, wherein the C 1-6 Alkyl, -OC 1-6 Alkyl, phenyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl; or R d1 and Re1 When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f1 replace; Each R f1 Choose independently the group consisting of the following items: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, phenyl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl; R 2 It is H, C 1-6 Alkyl, C 3-6 cycloalkyl or C 3-6 cycloalkyl-CH2-; B is selected from 5- to 12-membered heteroaryl groups or C 6-11 Aromatic cyclic groups; C is a heterocycle containing at least one nitrogen atom in the ring, and wherein -COOR 1 Part of it is bonded to the ring C via nitrogen atoms in the ring C; A is a cyclic group selected from 5-membered to 15-membered heteroaryl groups; V is selected from the following groups: -NH-, -C(O)N(H)-, -N(H)C(O)-, -S(O)(NH)-, -N(H)S(O)-, -S(O)N(H)-, -N(H)S(O)2- and -S(O)2N(H)-; Each R 3 and R 9 Choose independently the group consisting of: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=O)R b3 -C(=O)OR c3 -C(=O)NR d3 R e3 -NR d3 R e3 -NR d3 C(=O)Rb3 -OR c3 -SR c3 Wherein C 1-6 Alkyl, OC 1-6 Alkyl, C 3-6 Cycloalkyl, 3-7-membered heterocycloalkyl, 5-6-membered heteroaryl, and phenyl groups are optionally substituted by one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2; Where R b3 R c3 R d3 and R e3 Choose independently the group consisting of: hydrogen, hydroxyl, C 1-6 Halogenated alkyl, OC 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl and C 6-15 Aryl, wherein the C 1-6 Alkyl, -OC 1-6 Alkyl, C 6-15 Aryl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl; or R d3 and R e3 When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f3 replace; Each R f3Choose independently the group consisting of the following items: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl; Each R 4 Choose independently the group consisting of: hydroxyl, =O, halogen, -CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, C 6-11 Aryl, 5-11 heteroaryl, -C(=O)R b4 -C(=O)OR c4 -C(=O)NR d4 R e4 -NR d4 R e4 -NR d4 C(=O)R b4 -NR d4 C(=O)OR c4 -NR d4 C(=O)NR d4 R e4 -NR d4 S(=O)2R b4 -NR d4 S(=O)2NR d4 R e4 -OR c4 -SR c4 -OC(=O)R b4 -OC(=O)NR d4 R e4 -OC(=O)OR c4 -S(=O)2R c4 -S(=O)R c4 -OS(=O)R c4 -OS(=O)2R c4 -OS(=O)2OR c4 -S(=O)NR d4 R e4 -OS(=O)2NRd4 R e4 and -S(=O)2NR d4 R e4 Wherein C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl and C 6-11 The aryl group may optionally be substituted by one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl, phenyl, -NH2, -NHR' and -NR'R'', wherein R' and R'' are independently selected from C 1-6 Alkyl group, wherein the phenyl group is optionally hydroxyl, halogen, =O, -CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl and -OC 1-6 One or more alkyl groups are substituted; Where R b4 R c4 R d4 and R e4 Choose independently the group consisting of: hydrogen, hydroxyl, C 1-6 Halogenated alkyl groups, -OC 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl and C 6-15 Aryl, wherein the C 1-6 Alkyl, C 6-15 Aryl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl; or R d4 and R e4When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f4 replace; Each R f4 Choose independently the group consisting of the following items: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl; y1, y2, z1, and z2 are integers independently selected from 0, 1, 2, 3, and 4; L is the connector part; and M is the E3 ubiquitin ligase binding site.

[0010] In a second aspect, the present invention relates to a pharmaceutical composition comprising a compound according to the first aspect or a pharmaceutically acceptable salt, solvate or prodrug thereof, and one or more pharmaceutically acceptable excipients or carriers.

[0011] In another aspect, the present invention relates to a compound according to the first aspect or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to the second aspect, for use in therapy.

[0012] In another aspect, the present invention relates to a compound according to the first aspect or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to the second aspect, for the treatment or prevention of RIPK1-mediated diseases or conditions.

[0013] In another aspect, the present invention relates to a compound according to the first aspect or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to the second aspect, for the treatment or prevention of proliferative disorders, inflammatory diseases or conditions, neurodegenerative disorders or conditions, autoimmune disorders or conditions, or metabolic diseases or conditions.

[0014] In another aspect, the present invention relates to a compound according to the first aspect or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to the second aspect, for the treatment or prevention of cancer.

[0015] In another aspect, the present invention relates to a method for treating or preventing RIPK1-mediated diseases or conditions, the method comprising administering to a subject in need an effective amount of a compound according to the first aspect or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to the second aspect.

[0016] In another aspect, the present invention relates to a method for treating or preventing proliferative disorders, inflammatory diseases or conditions, neurodegenerative disorders or conditions, autoimmune disorders or conditions, or metabolic diseases or conditions, said method comprising administering to a subject in need an effective amount of a compound according to the first aspect or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition according to the second aspect.

[0017] In another aspect, the present invention relates to a method for treating or preventing cancer, the method comprising administering to a subject in need an effective amount of a compound according to the first aspect or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to the second aspect.

[0018] In another aspect, the present invention relates to a method for degrading proteins in cells, the method comprising delivering to the cells an effective amount of a compound according to a first aspect or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition according to a second aspect.

[0019] In another aspect, the present invention relates to a combination of a compound according to the first aspect or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition according to the second aspect, with one or more other therapeutic agents or treatments.

[0020] Preferred, suitable, and optional features of any particular aspect of the invention are also preferred, suitable, and optional features of any other aspect. Invention Details definition The compounds and intermediates described herein may be named according to the IUPAC (International Union for Pure and Applied Chemistry) or CAS (Chemical Abstracts Service) nomenclature systems. It should be understood that, unless explicitly stated to the contrary, the term "compound of Formula I" and the more general term "compound" refers to and includes any and all compounds described by and / or with reference to Formula I. It should also be understood that, unless otherwise specified, these terms cover all stereoisomers of such compounds in substantially pure form and all their salts, namely cis and trans isomers, as well as optical isomers, namely R and S enantiomers, and / or any mixtures of the foregoing in any ratio. This understanding extends to subformulas of Formula I and pharmaceutical compositions and therapeutic methods employing or containing one or more compounds of Formula I (alone or in combination with other agents).

[0022] The various hydrocarbon-containing portions provided in this article can be prefixed with the minimum and maximum number of carbon atoms in the specified portion, for example, "(C a-b ) or "C a -C b Use "" or "(ab)C" to describe it. For example, (C a-b Alkyl indicates an alkyl moiety having an integer number of carbon atoms from "a" to "b" (inclusive). Some moiety may also be described with or without specific reference to a particular atom or overall structure, depending on the minimum and maximum number of members. For example, the terms "a- to b-membered ring" or "having members between a and b" refer to a moiety having an integer number of atoms from "a" to "b" (inclusive).

[0023] When used in this document in conjunction with measurable values ​​such as quantities or time periods and similar values, “about” means to cover reasonable variations in that value, for example, to allow for experimental error in the measurement of said value.

[0024] When used alone or in combination with another or more terms herein, "alkyl" and "alkyl group" refer to a branched or unbranched saturated hydrocarbon chain. Unless otherwise specified, alkyl groups typically contain 1-10 carbon atoms, such as 1-6 carbon atoms, 1-4 carbon atoms, or 1-3 carbon atoms, and may be substituted or unsubstituted. Representative examples include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, isopropyl, tert-butyl, isobutyl, etc.

[0025] When used alone or in combination with another or more terms herein, "alkoxy" and "alkoxy group" refer to an O-alkyl group. Representative examples include, but are not limited to, -OMe, -OEt, -O- i Pr and O- t Bu. Unless otherwise indicated, the alkoxy group may be substituted or unsubstituted.

[0026] When used alone or in combination with another or more terms herein, "alkylene" and "alkylene group" refer to a branched or unbranched saturated hydrocarbon chain. Unless otherwise specified, alkylene groups typically contain 1-10 carbon atoms, such as 1-6 or 1-3 carbon atoms, and may be substituted or unsubstituted. Representative examples include, but are not limited to, methylene (-CH2-), ethylene isomers (-CH(CH3)- and -CH2CH2-), propylene isomers (-CH(CH3)CH2-, -CH(CH2CH3)-, -C(CH3)2- and -CH2CH2CH2-), etc.

[0027] When used alone or in combination with another or more terms herein, "alkenyl" and "alkenyl group" refer to a branched or unbranched hydrocarbon chain containing at least one double bond. Unless otherwise specified, alkenyl groups typically contain 2-10 carbon atoms, such as 2-6 or 2-4 carbon atoms, and may be substituted or unsubstituted. Representative examples include, but are not limited to, vinyl, 3-buten-1-yl, 2-vinylbutyl, and 3-hexen-1-yl.

[0028] When used alone or in combination with another or more terms herein, "alkynyl" and "alkynyl group" refer to a branched or unbranched hydrocarbon chain containing at least one triple bond. Unless otherwise specified, an alkynyl group typically contains 2-10 carbon atoms, such as 2-6 or 2-4 carbon atoms, and may be substituted or unsubstituted. Representative examples include, but are not limited to, ethynyl, 3-butyn-1-yl, propynyl, 2-butyn-1-yl, and 3-pentyn-1-yl.

[0029] As used herein, either alone or in combination with another or more terms, "heteroalkyl" refers to a stable straight or branched chain or combination thereof, comprising at least one carbon atom and at least one heteroatom (e.g., O, N, P, Si, and S), wherein the nitrogen and sulfur atoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized. The heteroatom may be located at any internal position of the heteroalkyl group or at a position where the alkyl group is attached to the remainder of the molecule. The heteroalkyl group is an uncyclic chain. Examples include, but are not limited to: -CH2-CH2-O-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -S(O)-CH3, -CH2-CH2-S(O)2-CH3, -CH=CH-O-CH3, -Si(CH3)3, -CH2-CH=N-OCH3, -CH=CH-N(CH3)-CH3, and polyvinyl chloride chains such as -(O(CH2)2). n (OCH2CH3). Up to two or three heteroatoms can be sequential, such as, for example, -CH2-NH-OCH3 and -CH2-O-Si(CH3)3. The heteroalkyl moiety may include one or more heteroatoms that may be the same or different.

[0030] Similarly, unless otherwise stated, the term "heteroalkylene" itself, or as part of another substituent, refers to a divalent group derived from a heteroalkylene group, as exemplified by -CH2-CH2-S-CH2-CH2- and -CH2-S-CH2-CH2-NH-CH2-, but is not limited thereto. For heteroalkylene groups, the heteroatom may also occupy any one or both of the chain ends (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, and similar groups).

[0031] When used alone or in combination with another or more terms herein, "aromatic" refers to monocyclic and polycyclic ring systems containing 4n+2 π electrons, where n is an integer. Aromatic should be understood to refer to and include ring systems containing only carbon atoms (i.e., "aryl") and ring systems containing at least one heteroatom selected from N, O, or S (i.e., "heteroaromatic" or "heteroaryl"). Aromatic ring systems may be substituted or unsubstituted.

[0032] As used herein, either alone or in combination with another or more terms, "non-aromatic" refers to a monocyclic or polycyclic ring system having at least one double bond that is not part of an extended conjugated π system. As used herein, non-aromatic means include and encompasses ring systems containing only carbon atoms and ring systems containing at least one heteroatom selected from N, O, or S. Non-aromatic ring systems may be substituted or unsubstituted.

[0033] When used alone or in combination with another or more terms herein, "aryl" and "aryl group" refer to phenyl and 7-15 membered bicyclic or tricyclic hydrocarbon ring systems, including bridging ring systems, spirocyclic systems, and / or fused ring systems, wherein at least one ring is aromatic. The aryl group may be substituted or unsubstituted. Unless otherwise specified, an aryl group may contain 6 ring atoms (i.e., phenyl) or 9 to 15 atoms, such as 9 to 11 ring atoms, or 9 or 10 ring atoms. Representative examples include, but are not limited to, naphthyl, indenyl, 1,2,3,4-tetrahydronaphthyl, 6,7,8,9-tetrahydro-5H-benzocycloheptenyl, and 6,7,8,9-tetrahydro-5H-benzocycloheptenyl. Suitably, the aryl group is phenyl and naphthyl, suitably phenyl.

[0034] As used herein, either alone or in combination with another or more terms, "arylalkyl" and "arylalkyl group" refer to an alkyl substituent in which a hydrogen atom is replaced by an aryl group, wherein the alkyl group and aryl group are as previously defined, such as, for example, benzyl (C6H5CH2-). The arylalkyl group may be substituted or unsubstituted.

[0035] When used alone or in combination with another or more terms herein, "carbocyclic group" and "carbocycle" refer to monocyclic and polycyclic ring systems containing only carbon atoms in the ring, i.e., hydrocarbon ring systems, without regard to or reference to aromaticity or degree of unsaturation. Therefore, "carbocyclic group" should be understood to refer to and include fully saturated ring systems (such as, for example, cyclohexyl groups), aromatic ring systems (such as, for example, phenyl groups), and ring systems having fully saturated, aromatic, and / or unsaturated moieties (such as, for example, cyclohexenyl, 2,3-dihydroindenyl, and 1,2,3,4-tetrahydronaphthyl). The terms "carbocyclic" and "carbocycle" also include bridging ring systems, fused ring systems, and spirocyclic ring systems.

[0036] When used alone or in combination with another or more terms herein, "cycloalkyl" and "cycloalkyl group" refer to a non-aromatic carbocyclic system that can be monocyclic, bicyclic, or tricyclic, saturated or unsaturated, and can be bridged, spirocyclic, and / or fused. Cycloalkyl groups can be substituted or unsubstituted. Unless otherwise specified, cycloalkyl groups typically contain from 3 to 12 ring atoms. In some cases, cycloalkyl groups may contain from 4 to 10 ring atoms (e.g., 4 ring atoms, 5 ring atoms, 6 ring atoms, 7 ring atoms, etc.). Representative examples include, but are not limited to, cyclopropyl, cyclopropenyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, norbornyl, norbornenyl, bicyclo[2.2.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.1]heptene, bicyclo[3.1.1]heptane, bicyclo[3.2.1]octane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, bicyclo[3.3.1]nonane, and bicyclo[3.3.2]decane. Suitably, the cycloalkyl group is selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups.

[0037] As used herein, either alone or in combination with another or more terms, "cycloalkylalkyl" and "cycloalkylalkyl group" refer to an alkyl substituent in which a hydrogen atom is replaced by a cycloalkyl group, wherein the alkyl group and cycloalkyl group are as previously defined, such as, for example, cyclohexylmethyl (C6H4H2O). 11 CH2-). The cycloalkyl group may be substituted or unsubstituted.

[0038] As used herein, either alone or in combination with another or more terms, "haloalkyl" and "haloalkyl group" refer to an alkyl group in which one or more hydrogen atoms are replaced by halogen atoms. Haloalkyl groups include saturated alkyl groups as well as unsaturated alkenyl and alkynyl groups. Representative examples include, but are not limited to, -CF3, -CHF2, -CH2F, -CF2CF3, -CHFCF3, -CH2CF3, -CF2CH3, -CHFCH3, -CF2CF2CF3, -CF2CH2CH3, -CF=CF2, -CCl=CH2, -CBr=CH2, -CI=CH2, -C≡C-CF3, -CHFCH2CH3, and -CHFCH2CF3. Haloalkyl groups may be substituted or unsubstituted. Suitably, the haloalkyl group is selected from CHF2 and CF3, preferably CF3.

[0039] When used alone or in combination with another or more terms herein, "haloalkoxy" and "haloalkoxy group" refer to an alkoxy group (i.e., an O-alkyl group) in which one or more hydrogen atoms are replaced by halogen atoms. Haloalkoxy groups include saturated alkoxy groups as well as unsaturated alkenyl and alkynyl groups. Representative examples include, but are not limited to, -OCF3, -OCHF2, -OCH2F, -OCF2CF3, -OCHFCF3, -OCH2CF3, -OCF2CH3, -OCHFCH3, -OCF2CF2CF3, -OCF2CH2CH3, -OCF=CF2, -OCCl=CH2, -OCBr=CH2, -OCHFCH2CH3, and -OCHFCH2CF3. The haloalkoxy group may be substituted or unsubstituted. Suitably, the haloalkoxy group is selected from -OCHF2 and -OCF3, suitably -OCF3.

[0040] When used alone or in combination with another or more terms herein, “halo” and “halogen” include fluorine, chlorine, bromine and iodine atoms and substituents.

[0041] As used herein, either alone or in combination with another or more terms, "heteroaryl" and "heteroaryl group" refer to (a) a 5- or 6-membered monocyclic aromatic ring containing at least one heteroatom, such as nitrogen, oxygen, or sulfur, in addition to a carbon atom, and (b) a 7- to 15-membered bicyclic and tricyclic ring containing at least one heteroatom, such as nitrogen, oxygen, or sulfur, in addition to a carbon atom, and wherein at least one ring is aromatic. In some cases, a heteroaryl group may contain two or more heteroatoms, which may be the same or different. A heteroaryl group may be substituted or unsubstituted, and may be bridged, spiro, and / or fused. In some cases, a heteroaryl group may contain 5, 6, or 8 to 15 ring atoms. In other cases, a heteroaryl group may contain 5 to 10 ring atoms, such as 5, 6, 9, or 10 ring atoms. Representative examples include, but are not limited to, 2,3-dihydrobenzofuranyl, 1,2-dihydroquinolinyl, 3,4-dihydroisoquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, benzoxazinyl, benzothiazinyl, chromanyl, furanyl, 2-furanyl, 3-furanyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, oxazolyl, pyridinyl, 2-pyridinyl, 3-pyridinyl or 4-pyridinyl, pyrimidinyl, 2-pyrimidinyl, 4-pyrimidinyl or 5-pyrimidinyl, pyrazolyl, pyrroleyl, 2-pyrroleyl or 3-pyrroleyl, pyrazinyl, pyridazinyl, 3-pyridazinyl or 4-pyridazinyl, 2-pyrazinyl, thiophenyl, 2-thiophenyl, 3-thiophenyl, tetrazolyl, thiazolyl, thiadiazolyl, triazinyl. Triazolyl, pyridin-2-yl, pyridin-4-yl, pyrimidin-2-yl, pyridazin-4-yl, pyrazin-2-yl, naphridinyl, pteridinyl, phthalazinyl, purinyl, alloxazinyl, benzimidazolyl, benzofuranyl, benzofuranyl, 2H-1-benzopyranyl, benzothiadiazine, benzothiazinyl, benzothiazolyl, benzothiopheneyl, benzoxazolyl, zolinyl, furanopyridinyl, dihydroindolyl, indazinyl, indolyl, or 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl or 7-indolyl, 3H-indolyl, quinazolinyl, quinoxolinyl, isoindolyl, isoquinolinyl, 10-aza-tricyclic [6.3.1.0] 2,7 [6.3.1.0] Dodecane-2(7),3,5-trienyl, 12-oxa-10-aza-tricyclic [6.3.1.0] 2,7 [Dodecane-2(7),3,5-trienyl, 12-aza-tricyclo[7.2.1.0]] 2,7 [Dodecane-2(7),3,5-trienyl,10-aza-tricyclo[6.3.2.0]] 2,7[Tridecane-2(7),3,5-trienyl, 2,3,4,5-tetrahydro-1H-benzo[d]azapyryl, 1,3,4,5-tetrahydro-benzo[d]azapyr-2-one, 1,3,4,5-tetrahydro-benzo[b]azapyr-2-one, 2,3,4,5-tetrahydro-benzo[c]azapyr-1-one, 1,2,3,4-tetrahydro-benzo[e][1,4]diazapyr-5-one, 2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazapyryl, 5,6,8,9-tetrahydro-7-oxa-benzocycloheptenyl, 2, 3,4,5-Tetrahydro-1H-benzo[b]azapyridine, 1,2,4,5-tetrahydro-benzo[e][1,3]diazapyridine-3-one, 3,4-dihydro-2H-benzo[b][1,4]dioxacycloheptenyl, 3,4-dihydro-2H-benzo[f][1,4]oxazapyridine-5-one, 6,7,8,9-tetrahydro-5-thia-8-aza-benzocycloheptenyl, 5,5-dioxo-6,7,8,9-tetrahydro-5-thia-8-aza-benzocycloheptenyl, and 2,3,4,5-tetrahydro-benzo[f][1,4]oxazapyridine. Suitably, the heteroaryl group is a 5- or 6-membered heteroaryl ring containing one, two, or three heteroatoms selected from N, O, or S.

[0042] As used herein, either alone or in combination with another or more terms, "heteroarylalkyl" and "heteroarylalkyl group" refer to an alkyl substituent in which a hydrogen atom is replaced by a heteroaryl group, wherein the alkyl group and the heteroaryl group are as previously defined. The heteroarylalkyl group may be substituted or unsubstituted. Where the number of carbon atoms is provided, for example, heteroaryl (C... n-m Alkyl, in this range, refers to an alkyl group. Suitablely, the constituent alkyl group has 1-6 carbons, suitablely 1-3 carbons.

[0043] When used alone or in combination with another or more terms herein, "heterocyclic group" and "heterocycle" refer to monocyclic and polycyclic ring systems containing a carbon atom and at least one heteroatom selected from nitrogen, oxygen, sulfur, or phosphorus, without regard to or reference to aromaticity or degree of unsaturation. Thus, a heterocyclic group should be understood to refer to and include fully saturated ring systems (such as, for example, piperidinyl groups), aromatic ring systems (such as, for example, pyridinyl groups), and ring systems having fully saturated, aromatic, and / or unsaturated moieties (such as, for example, 1,2,3,6-tetrahydropyridinyl and 2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-1-yl). The terms heterocyclic and heterocycle also include bridging ring systems, fused ring systems, and spirocyclic ring systems.

[0044] As used herein, either alone or in combination with another or more terms, "heterocyclic alkyl" and "heterocyclic alkyl group" refer to a non-aromatic ring system of 3 to 15 members, including monocyclic, bicyclic, and tricyclic rings, containing at least one heteroatom in addition to a carbon atom, such as nitrogen, oxygen, sulfur, or phosphorus. Heterocyclic alkyl groups can be fully saturated or contain unsaturated portions, and can be bridged ring systems, spirocyclic systems, and / or fused ring systems. In some cases, heterocyclic alkyl groups may contain at least two or more heteroatoms, which may be the same or different. Heterocyclic alkyl groups may be substituted or unsubstituted. In some cases, heterocyclic alkyl groups may contain from 3 to 10 ring atoms, or from 3 to 7 ring atoms, or from 5 to 7 ring atoms, such as 5, 6, or 7 ring atoms.Representative examples include, but are not limited to, tetrahydrofuranyl, pyrrolylyl, pyrrolinyl, imidazoylyl, imidazolinyl, pyrazoleyl, pyrazolelinyl, piperidinyl, piperazine, dihydroindolyl, isodihydroindolyl, morpholinyl, thiomorpholinyl, homomorpholinyl, homopiperidinyl, homopiperazine, thiomorpholinyl-5-oxide, thiomorpholinyl-S,S-dioxide, pyrrolylyl, tetrahydropyranyl, piperidinyl, tetrahydrothiophenyl, homopiperidinyl, homothiomorpholinyl-S,S-dioxide, oxazolidinone, dihydropyrazole, dihydropyrrolyl, dihydropyrazine, dihydropyridine Pyridyl, dihydropyrimidinyl, dihydrofuranyl, dihydropyranyl, tetrahydrothiophene-5-oxide, tetrahydrothiophene-S,S-dioxide, high-thiomorpholinyl-5-oxide, quininecycloyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, 8-oxa-3-azabicyclo[3.2.1]octyl, 3,8-diazabicyclo[3.2.1]octyl, 2,5-diazabicyclo[2.2.1]heptyl, 3,8-diazabicyclo[3.2.1]octyl, 3,9-diazabicyclo[4.2.1] [3.2.2]Nonyl, [1,4]oxaphosphinanyl-4-oxide, [1,4]oxaphosphinanyl-4-oxide, [1,2]oxaphospholanyl-2-oxide, phosphacyclohexyl-1-oxide, [1,3]oxaphosphinanyl-3-oxide, [1,3]oxaphosphinanyl-3-oxide Alkyl-3-oxides, 7-oxabicyclo[2.2.1]heptyl, 6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl, 6,8-dihydro-5H-imidazo[1,5-a]pyrazin-7-yl, 6,8-dihydro-5H-imidazo[1,2-a]pyrazin-7-yl, 5,6,8,9-tetrahydro-[1,2,4]triazolo[4,3-d][1,4]diazazo-7-yl, and 6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl. Suitably, a heterocyclic alkyl group as defined herein is a monocyclic heterocyclic group, a bicyclic heterocyclic group, or a spirocyclic group containing one, two, or three heteroatoms selected from N, O, or S.

[0045] As used herein, either alone or in combination with another or more terms, "heterocyclic alkyl alkyl" and "heterocyclic alkyl group" refer to an alkyl substituent in which a hydrogen atom is replaced by a heterocyclic alkyl group, wherein the alkyl group and heterocyclic alkyl group are as previously defined, such as, for example, pyrrolidinylmethyl (C4H8NCH2-). The heterocyclic alkyl group may be substituted or unsubstituted. Where the number of carbon atoms is provided, for example, heterocyclic alkyl (C4H8NCH2-)n-m Alkyl, in this range, refers to an alkyl group. Suitablely, the constituent alkyl group has 1-6 carbons, suitablely 1-3 carbons.

[0046] As used in this article, "oxo" refers to the double bond with oxygen, i.e., =O.

[0047] As used alone or in combination with another or more terms herein, “pharmaceutical acceptable” means a material that is generally chemically and / or physically compatible with other components (such as, for example, the reference formulation) and / or generally physiologically compatible with its recipients (such as, for example, the subject).

[0048] As used herein, either alone or in combination with another or more terms, "pharmaceutical composition" means a composition that can be used to treat a disease, condition or disorder in a subject (including humans).

[0049] As used herein, either alone or in combination with another or more terms, "stable" and "chemically stable" mean a compound that is robust enough to be separated from the reaction mixture with useful purity. This application relates only to the preparation of stable compounds. When a list of alternative substituents includes members that cannot be used to substitute a particular group due to valence requirements, chemical stability, or other reasons, the list is intended to be interpreted, in context, to include those list members suitable for substituting the particular group. For example, when considering the degree of optional substitution of a particular moiety, it should be understood that the number of substituents does not exceed the valence suitable for that moiety.

[0050] When used alone or in combination with another or more terms in this document, “subject” and “patient” appropriately refer to mammals, particularly humans.

[0051] When used alone or in combination with another or more terms herein, “substituted” indicates that a hydrogen atom on a molecule has been replaced by a different atom or group of atoms, and the atom or group of atoms that replaces the hydrogen atom is a “substituent”. It should be understood that the terms “substituent,” “substituents,” “moiety,” “moieties,” “group,” or “groups” refer to substituents.

[0052] When used alone or in combination with another or more terms herein, “therapeutic” and “therapeuticly effective amount” refer to an amount of a compound, composition, or drug that (a) inhibits or causes improvement of a particular disease, condition, or disorder; or (b) alleviates, improves, or eliminates one or more symptoms of a particular disease, condition, or disorder. It should be understood that the terms “therapeutic” and “therapeuticly effective” cover any of the effects (a)-(b) mentioned above, alone or in combination with any of the other effects (a)-(b). It should be understood that, in, for example, humans or other mammals, a therapeutically effective amount can be determined experimentally in a laboratory or clinical setting, or a therapeutically effective amount can be the amount required by the guidance of the U.S. Food and Drug Administration (FDA) or an equivalent foreign regulatory agency for the specific disease being treated and the subject. It should be understood that the determination of the appropriate dosage form, dosage, and route of administration is within the level of a person of ordinary skill in the pharmaceutical and medical fields.

[0053] As used herein, whether alone or in combination with another or more terms, “treating,” “treated,” and “treatment” refer to and include improving, palliative, and curative uses and outcomes. In some embodiments, the terms “treating,” “treated,” and “treatment” refer to curative uses and outcomes as well as uses and outcomes that reduce or lessen the severity of a particular condition, feature, symptom, disorder, or disease described herein. For example, treatment may include reducing certain symptoms of a condition or disorder or completely eradicating said condition or disorder.

[0054] As used herein, the terms “prevent,” “preventative,” or “prevention” mean reducing the likelihood or delaying the onset of one or more symptoms of a particular disease, condition, or disorder described herein. It should be understood that the terms “prevent,” “preventative,” or “prevention” are not necessarily used in an absolute sense, but rather refer to the use and result of the application of the compound or composition therein reducing the likelihood or severity of the condition, symptoms, or disease state and / or delaying the onset of the condition, symptoms, or disease state for a period of time.

[0055] As used herein, “therapeutic agent” or “therapeutic active agent,” whether used alone or in combination with another or more terms, means any compound that has been found to be effective in treating a disease, disorder, or condition and is not described by Formula I, i.e., a drug. It should be understood that therapeutic agents may or may not be approved by the FDA or an equivalent foreign regulatory agency.

[0056] "Effective amount" means the amount of a compound that is sufficient to achieve such treatment of a disease when administered to a subject or patient for the purpose of treating the disease. The "effective amount" will vary depending on the compound, the disease and its severity, and the age, weight, etc., of the subject or patient to be treated.

[0057] by" "or" "A terminated bond represents that the bond is attached to another atom not shown in the structure. Unless otherwise defined, a bond that terminates inside the ring structure rather than at an atom in the ring structure represents that the bond may be variably attached to an atom in the ring structure as permitted by its valence."

[0058] As used herein, the term "part" refers to a portion or functional group of a molecule. A chemical part is generally considered to be a chemical entity embedded in or attached to a molecule.

[0059] In one aspect, the present invention relates to a compound of formula I or a salt, solvate, or prodrug thereof: in Q is the formula Q 1 or Q 2 Protein-binding portion: (Q 1 ) (Q 2 ) in R 1 Choose the group consisting of the following items: C 3-11 cycloalkyl, C 3-11 cycloalkyl (C 1-3 )alkyl, 3- to 12-membered heterocyclic alkyl, 3- to 12-membered heterocyclic alkyl (C 1-3 )alkyl, 5- to 12-membered heteroaryl (C 1-6 )alkyl, C 1-10 Alkyl, C 2-10 alkenyl and C 2-10 Alkyne groups, wherein each is optionally surrounded by one or more R groups a1 replace; Each R a1 Choose independently the group consisting of: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6cycloalkyl, -OC 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=O)R b1 -C(=O)NR d1 R e1 -NR d1 R e1 -NR d1 C(=O)R b1 -OR c1 -SR c1 -OC(=O)R b1 -S(=O)2R c1 and -S(=O)2NR d1 R e1 Wherein C 1-6 Alkyl, OC 1-6 Alkyl, C 3-6 cycloalkyl, -OC 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl and C 6-11 The aryl group may optionally be substituted by one or more groups selected from the following: hydroxyl, halogen, =O, -CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl, phenyl, -C(O)C 1-6 Alkyl, -C(O)N(H)C 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl group 2, -CONH2, -C(O)N(H)C 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl)2、-N(H)C 1-6 Alkyl and -N(C) 1-6 Alkyl)2; Where R b1 R c1 R d1 and R e1 Choose independently the group consisting of: hydrogen, hydroxyl, C 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 alkyl and phenyl, wherein the C 1-6 Alkyl, -OC 1-6 Alkyl, phenyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl; or R d1 and R e1 When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f1 replace; Each R f1 Choose independently the group consisting of the following items: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, phenyl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl; R 2 It is H, C 1-6 Alkyl, C 3-6 cycloalkyl or C 3-6 cycloalkyl-CH2-; B is selected from 5- to 12-membered heteroaryl groups or C 6-11 Aromatic cyclic groups; C is a heterocycle containing at least one nitrogen atom in the ring, and wherein -COOR 1 Part of it is bonded to the ring C via nitrogen atoms in the ring C; A is a cyclic group selected from 5-membered to 15-membered heteroaryl groups; V is selected from the following groups: -NH-, -C(O)N(H)-, -N(H)C(O)-, -S(O)(NH)-, -N(H)S(O)-, -S(O)N(H)-, -N(H)S(O)2- and -S(O)2N(H)-; R 3 and R 9 Choose independently the group consisting of: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=O)R b3 -C(=O)OR c3 -C(=O)NR d3 R e3 -NR d3 R e3 -NR d3 C(=O)R b3 -OR c3 -SR c3 Wherein C 1-6 Alkyl, OC 1-6 Alkyl, C 3-6 Cycloalkyl, 3-7-membered heterocycloalkyl, 5-6-membered heteroaryl, and phenyl groups are optionally substituted by one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2; Where R b3 R c3 R d3 and R e3 Choose independently the group consisting of: hydrogen, hydroxyl, C 1-6 Halogenated alkyl, OC 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl and C 6-15 Aryl, wherein the C 1-6 Alkyl, -OC 1-6 Alkyl, C 6-15 Aryl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC1-6 Alkyl; or R d3 and R e3 When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f3 replace; Each R f3 Choose independently the group consisting of the following items: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl; R 4 Choose from the group consisting of: hydroxyl, =O, halogen, -CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, C 6-11 Aryl, 5-11 heteroaryl, -C(=O)R b4 -C(=O)OR c4 -C(=O)NR d4 R e4 -NR d4 R e4 -NR d4 C(=O)R b4 -NR d4 C(=O)OR c4 -NR d4 C(=O)NR d4 R e4 -NR d4 S(=O)2R b4 -NR d4 S(=O)2NR d4 R e4 -OR c4 -SR c4 -OC(=O)R b4 -OC(=O)NR d4 R e4 -OC(=O)ORc4 -S(=O)2R c4 -S(=O)R c4 -OS(=O)R c4 -OS(=O)2R c4 -OS(=O)2OR c4 -S(=O)NR d4 R e4 -OS(=O)2NR d4 R e4 and -S(=O)2NR d4 R e4 Wherein C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl and C 6-11 The aryl group may optionally be substituted by one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl, phenyl, -NH2, -NHR' and -NR'R'', wherein R' and R'' are independently selected from C 1-6 Alkyl group, wherein the phenyl group is optionally hydroxyl, halogen, =O, -CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl and -OC 1-6 One or more alkyl groups are substituted; Where R b4 R c4 R d4 and R e4 Choose independently the group consisting of: hydrogen, hydroxyl, C 1-6 Halogenated alkyl groups, -OC 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl and C 6-15 Aryl, wherein the C 1-6 Alkyl, C 6-15 Aryl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C)1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl; or R d4 and R e4 When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f4 replace; Each R f4 Choose independently the group consisting of the following items: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl; y1, y2, z1, and z2 are integers independently selected from 0, 1, 2, 3, and 4; L is the connector part; and M is the E3 ubiquitin ligase binding site.

[0060] Protein-binding part Q Q is the protein-binding portion and is used to provide the compound of Formula I with specific binding specificity to the target protein prior to subsequent ubiquitination and degradation of the target protein.

[0061] In one embodiment, Q is the RIPK1 kinase binding moiety. Therefore, compounds of formula I can be used as RIPK1 kinase degraders and thus find utility in treating or preventing diseases or conditions mediated by RIPK1 kinase.

[0062] In one implementation, Q is the formula Q 1 Protein-binding portion: (Q 1 ).

[0063] In one implementation, R 1 Choose the group consisting of the following items: C 3-11 cycloalkyl, C 3-11 cycloalkyl (C 1-3 )alkyl, 3- to 12-membered heterocyclic alkyl, 3- to 12-membered heterocyclic alkyl (C1-3 )alkyl, C 1-10 Alkyl, C 2-10 alkenyl and C 2-10 Alkyne groups, wherein each is optionally surrounded by one or more R groups a1 replace.

[0064] In another implementation, R 1 Choose the group consisting of the following items: C 3-11 Cycloalkyl, 3- to 12-membered heterocycloalkyl, C 1-10 Alkyl, C 2-10 alkenyl and C 2-10 Alkyne groups, wherein each is optionally surrounded by one or more R groups a1 replace.

[0065] In another implementation, R 1 Choose the group consisting of the following items: C 3-7 cycloalkyl, C 3-7 cycloalkyl (C 1-3 )alkyl, 3- to 7-membered heterocyclic alkyl, 3- to 7-membered heterocyclic alkyl (C 1-3 )alkyl, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne groups, wherein each is optionally surrounded by one or more R groups a1 replace.

[0066] In another implementation, R 1 Choose the group consisting of the following items: C 3-7 Cycloalkyl, 3- to 7-membered heterocycloalkyl, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne groups, wherein each is optionally surrounded by one or more R groups a1 replace.

[0067] In another implementation, R 1 Choose the group consisting of the following items: C 3-7 Cycloalkyl, 3- to 7-membered heterocycloalkyl and C 1-6 Alkyl groups, wherein each is optionally surrounded by one or more R groups a1 replace.

[0068] In another implementation, R 1 Selected from the following groups, each optionally bound by one or more R groups a1 replace: .

[0069] In another implementation, R1 Selected from the following groups, each optionally bound by one or more R groups a1 replace: .

[0070] In another implementation, R 1 Selected from the following groups, each optionally bound by one or more R groups a1 replace: .

[0071] In another implementation, R 1 It is a cyclohexyl group or an isopropyl group.

[0072] In one implementation scheme, each R a1 Choose independently the group consisting of: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -OC 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=O)R b1 -NR d1 R e1 -OR c1 Wherein C 1-6 Alkyl, OC 1-6 Alkyl, C 3-6 cycloalkyl, -OC 3-6 Cycloalkyl, 3-7-membered heterocycloalkyl, 5-6-membered heteroaryl, and phenyl groups are optionally substituted by one or more groups selected from the following: hydroxyl, halogen, =O, -CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl, phenyl, -C(O)C 1-6 Alkyl, -C(O)N(H)C 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl group 2, -CONH2, -C(O)N(H)C 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl)2、-N(H)C 1-6 Alkyl and -N(C) 1-6Alkyl)2.

[0073] In another implementation, each R a1 Choose independently the group consisting of: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 3-6 cycloalkyl, -OC 3-6 Cycloalkyl, -C(=O)R b1 -NR d1 R e1 -OR c1 Wherein C 1-6 Alkyl, OC 1-6 Alkyl, C 3-6 cycloalkyl and -OC 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, -CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl, phenyl, -C(O)C 1-6 Alkyl group, -C(O)N(H)C 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl group 2, -CONH2, -C(O)N(H)C 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl)2、-N(H)C 1-6 Alkyl and -N(C) 1-6 Alkyl)2.

[0074] In another implementation, each R a1 Choose independently the group consisting of: hydroxyl, =O, halogen, CN, CF3, OCF3, C 1-6 Alkyl, OC 1-6 Alkyl, -C(=O)R b1 -NR d1 R e1 and -OR c1 .

[0075] In another implementation, each R a1 Choose independently the group consisting of: hydroxyl, =O, halogen, CN, CF3, OCF3, C 1-6 Alkyl, OC 1-6 Alkyl, -C(=O)Me, -NH2, -N(H)C 1-3Alkyl and -N(C) 1-3 Alkyl)2.

[0076] In one implementation scheme, each R b1 Independently selected from hydrogen and C 3-6 cycloalkyl or C 1-6 Alkyl group. In another embodiment, each R b1 Selected independently from C 3-6 cycloalkyl or C 1-4 alkyl.

[0077] In one implementation scheme, each R c1 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 alkyl and phenyl, wherein the C 1-6 Alkyl, phenyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0078] In another implementation, each R c1 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, C 3-6 cycloalkyl and C 1-6 Alkyl, wherein the C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl group. In another embodiment, each R c1 Independently selected from hydrogen or C 1-6 alkyl.

[0079] In one implementation scheme, each Rd1 Independently selectable hydrogen and C 3-6 cycloalkyl and C 1-6 The group consisting of alkyl groups, wherein the C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl group. In another embodiment, each R d1 Independently selected from hydrogen or C 1-6 alkyl.

[0080] In one implementation scheme, each R e1 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 alkyl and phenyl, wherein the C 1-6 Alkyl, phenyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0081] In another implementation, each R e1 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, C 3-6 cycloalkyl and C 1-6 Alkyl, wherein the C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl group. In another embodiment, each R e1 Independently selected from hydrogen or C 1-6 alkyl.

[0082] In one implementation, R d1 and R e1 When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f1 replace.

[0083] In another implementation, R d1 and R e1 When attached to the same atom, they form a 5-7 membered ring together with the atom to which they are attached, the 5-7 membered ring optionally containing one or more heteroatoms selected from O, N, and S, and wherein the ring is optionally surrounded by one or more R atoms. f1 replace.

[0084] In one implementation, R f1 Choose from the following groups: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 1-6 Alkyl and -OC 1-6 Alkyl group. In another embodiment, R f1 Selected from hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-4 Alkyl, -N(C) 1-4 Alkyl)2, C 1-4 Haloalkyl, C 1-4 Alkyl and -OC 1-4 alkyl.

[0085] In one implementation, R 2 Choose free hydrogen, C 1-6 Alkyl, C 3-6 The group consisting of cycloalkyl groups. In another embodiment, R 2 Is it hydrogen or C? 1-6 Alkyl group. In another embodiment, R 2 Is it hydrogen or C? 1-3 Alkyl group. In another embodiment, R 2 It is hydrogen, methyl, or ethyl. In another embodiment, R 2It is either hydrogen or methyl.

[0086] In one embodiment, B is selected from 5-membered to 12-membered heteroaryl groups and C. 6-11 A cyclic aryl group. In another embodiment, B is a cyclic group selected from 5- to 6-membered heteroaryl groups and phenyl groups.

[0087] In one embodiment, B is a 6-membered heteroaryl ring or a phenyl group containing one or more nitrogen atoms. In another embodiment, B is a pyridine ring or a phenyl group.

[0088] In another embodiment, B is a group of formula B1: (B1) Where X 9 and X 10 Independently selected from N and CR 3 Or CH.

[0089] In one implementation, X 9 It is N. In another implementation, X 9 It is N and X 10 It is CR 3 Or CH.

[0090] In one implementation, X 9 It is N and X 10 It is CH, and R 2 It is a methyl group.

[0091] In another embodiment, B is a group of formula B2: (B2)

[0092] In another implementation, ring B is .

[0093] In one embodiment, the wavy line in ring B, B1, or B2 in the example above indicates the attachment point with the adjacent ring A. In another embodiment, the dashed line in B, B1, or B2 indicates the attachment point with the adjacent ring A.

[0094] In one implementation, R 3 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cycloalkyl, -C(=O)R b3-C(=O)OR c3 -C(=O)NR d3 R e3 -NR d3 R e3 -NR d3 C(=O)R b3 -OR c3 -SR c3 Wherein C 1-6 Alkyl, OC 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0095] In another implementation, R 3 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -NR d3 R e3 -OR c3 -SR c3 Wherein C 1-6 Alkyl, OC 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0096] In another implementation, R 3 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -NR d3 R e3 Wherein C 1-6 Alkyl and OC 1-6 The alkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0097] In another implementation, R 3 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0098] In another implementation, R 3 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 1-4 Alkyl, OC 1-4 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0099] In another implementation, R 3 Choose from the group consisting of: hydroxyl, =O, Cl, Br, CN, CF3, OCF3, methyl, ethyl, and OMe.

[0100] In one implementation scheme, each R b3 Independently selected from hydrogen and C 3-6 cycloalkyl or C 1-6 Alkyl group. In another embodiment, each R b3 Selected independently from C 3-6 cycloalkyl or C 1-4alkyl.

[0101] In one implementation scheme, each R c3 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 alkyl and phenyl, wherein the C 1-6 Alkyl, phenyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0102] In another implementation, each R c3 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, C 3-6 cycloalkyl and C 1-6 Alkyl, wherein the C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl group. In another embodiment, each R c3 Independently selected from hydrogen or C 1-6 alkyl.

[0103] In one implementation scheme, each R d3 Independently selectable hydrogen and C 3-6 cycloalkyl and C 1-6 The group consisting of alkyl groups, wherein the C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl group. In another embodiment, each R d3 Independently selected from hydrogen or C 1-6 alkyl.

[0104] In one implementation scheme, each R e3 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 alkyl and phenyl, wherein the C 1-6 Alkyl, phenyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0105] In another implementation, each R e3 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, C 3-6 cycloalkyl and C 1-6 Alkyl, wherein the C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl group. In another embodiment, each R e3 Independently selected from hydrogen or C 1-6 alkyl.

[0106] In one implementation, R d3 and R e3When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f3 replace.

[0107] In another implementation, R d3 and R e3 When attached to the same atom, they form a 5-7 membered ring together with the atom to which they are attached, the 5-7 membered ring optionally containing one or more heteroatoms selected from O, N, and S, and wherein the ring is optionally surrounded by one or more R atoms. f3 replace.

[0108] In one implementation, R f3 Choose from the following groups: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 1-6 Alkyl and -OC 1-6 Alkyl group. In another embodiment, R f3 Selected from hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-4 Alkyl, -N(C) 1-4 Alkyl)2, C 1-4 Haloalkyl, C 1-4 Alkyl and -OC 1-4 alkyl.

[0109] In one implementation, y1 is an integer selected from 0, 1, and 2. In another implementation, y1 is 1. In yet another implementation, y1 is 0.

[0110] In one embodiment, A is a cyclic group selected from 5- to 12-membered heteroaryl groups. In another embodiment, A is an 8- to 10-membered fused bicyclic heteroaryl group; in yet another embodiment, A is a 9- or 10-membered fused bicyclic heteroaryl group; and in yet another embodiment, A is a 9- or 10-membered fused bicyclic heteroaryl group suitably containing at least one nitrogen atom.

[0111] In another embodiment, A is a cyclic group selected from benzothiazolyl, aza-benzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridyl, imidazopyrazinyl, imidazopyrazinyl, triazolopyridyl, pyrazolopyridyl, benzofurazanyl, benzothiadiazinyl, benzothiazinyl, benzooxazolyl, aza-benzooxazolyl, aza-indolyl, cenolinyl, furan-pyridyl, quinazolinyl, quinoxolinyl, and isoquinolinyl.

[0112] In another embodiment, A is a cyclic group selected from benzothiazolyl, azido-benzothiazolyl, benzimidazolyl, azido-benzimidazolyl, imidazopyridyl, benzofurazanyl, benzothiadiazinyl, benzothiazinyl, benzooxazolyl, azido-benzooxazolyl, azido-indolyl, zolinyl, furan-pyridyl, quinazolinyl, quinoxolinyl, and isoquinolinyl.

[0113] In another embodiment, A is a cyclic group selected from benzothiazolyl, aza-benzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridyl, benzoxazolyl, aza-benzoxazolyl, aza-indolyl, cenolinyl, quinazolinyl, quinoxolinyl, and isoquinolinyl.

[0114] In another embodiment, A is a cyclic group selected from benzothiazolyl, aza-benzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridyl, benzoxazolyl, aza-benzoxazolyl, and aza-indolyl.

[0115] In another embodiment, A is a cyclic group selected from benzothiazolyl, aza-benzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridyl, benzoxazolyl, aza-benzoxazolyl, and aza-indolyl.

[0116] In another embodiment, A is a cyclic group selected from benzothiazolyl, aza-benzothiazolyl, and imidazopyridyl.

[0117] In another embodiment, A is a cyclic group of formula A1. (A1) Where X 1 X 2 X 3 and X 4 Independently selected from C, N, CH or CR 4 The condition is X 1 X 2 X 3 and X 4 Only one of them is C and forms an attachment point with ring B; X 5 and X 6 Independently selected from N or C; X 7 and X 8 Independently selected from O, S, N, CH, CR 4 and NR 4 ; The condition is X 1 X 2 X 3X 4 X 5 X 6 X 7 and X 8 At least one of them must be N.

[0118] In one implementation, X 8 It is N.

[0119] In one implementation, X 7 It is S or CH.

[0120] In one implementation, X 1 X 2 X 3 and X 4 Each of them is C, CH or CR 4 The condition is X 1 X 2 X 3 and X 4 Only one of them is C and forms an attachment point with ring B.

[0121] In one implementation, X 2 It is C and forms an attachment point with ring B, and X 1 X 3 and X 4 Independently selected from N, CH or CR 4 Appropriately, X 1 X 3 and X 4 Independently selected from CH or CR 4 .

[0122] In another embodiment, A is a cyclic group of formula A2. (A2) Where X 1 X 2 X 3 and X 4 Independently selected from C, N, CH or CR 4 The condition is X 1 X 2 X 3 and X 4 Only one of them is C and forms an attachment point with ring B.

[0123] In one implementation of A2, X 1 X 2 X 3 and X 4 Only one of them is N. In another implementation, X... 1 X2 X 3 and X 4 Each of them is independently selected from C, CH or CR. 4 The condition is X 1 X 2 X 3 and X 4 Only one of them is C and forms an attachment point with ring B.

[0124] In one implementation, X 2 It is C and forms an attachment point with ring B, and X 1 X 3 and X 4 Independently selected from N, CH or CR 4 Appropriately, X 1 X 3 and X 4 Independently selected from CH or CR 4 .

[0125] In another embodiment, A is a cyclic group of formula A3. (A3) Where X 11 X 12 X 13 and X 4 Independently selected from C, N, CH or CR 4 The condition is X 11 X 12 X 13 and X 4 Only one of them is C and forms an attachment point with ring B.

[0126] In one implementation, X 13 It is C and forms an attachment point with ring B, and X 11 X 12 and X 14 Independently selected from N, CH or CR 4 In one such implementation, X 11 X 12 and X 14 Independently selected from CH or CR 4 In another implementation, X 12 It is N or CH, and X 11 and X 14 Independently selected from CH or CR 4 .

[0127] In another such implementation, X 12 It is N, and X 11 and X14 Independently selected from CH or CR 4 .

[0128] In one embodiment, A is a cyclic group selected from the following: , Each of them can be optionally controlled by one or more Rs 4 replace.

[0129] In another embodiment, A is a cyclic group selected from the following: , Each of them can be optionally controlled by one or more Rs 4 replace.

[0130] In another embodiment, A is a cyclic group selected from the following: , Each of them can be optionally controlled by one or more Rs 4 replace.

[0131] In one embodiment, the wavy line in the examples of ring A above or in formulas A1 to A3 indicates the attachment point with the adjacent group V. In another embodiment, the wavy line in the examples of ring A above or in formulas A1 to A3 indicates the attachment point with the adjacent ring B.

[0132] In one implementation, R 4 Selected from hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=O)R b3 -C(=O)OR c4 -C(=O)NR d4 R e4 -NR d4 R e4 -NR d4 C(=O)R b4 -OR c4 -SR c4 Wherein C 1-6 Alkyl, OC 1-6 Alkyl, C 3-6Cycloalkyl, 3-7-membered heterocycloalkyl, 5-6-membered heteroaryl, and phenyl groups are optionally substituted by one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0133] In one implementation, R 4 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cycloalkyl, -C(=O)R b4 -C(=O)OR c4 -C(=O)NR d4 R e4 -NR d4 R e4 -NR d4 C(=O)R b4 -OR c4 -SR c4 Wherein C 1-6 Alkyl, OC 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0134] In another implementation, R 4 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C3-6 cycloalkyl, -NR d4 R e4 -OR c4 -SR c4 Wherein C 1-6 Alkyl, OC 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0135] In another implementation, R 4 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -NR d4 R e4 Wherein C 1-6 Alkyl and OC 1-6 The alkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0136] In another implementation, R 4 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0137] In another implementation, R 4 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 1-4 Alkyl, OC 1-4 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0138] In another implementation, R 4 Choose from the group consisting of: hydroxyl, =O, Cl, Br, CN, CF3, OCF3, methyl, ethyl, and OMe.

[0139] In one implementation scheme, each R b4 Independently selected from hydrogen and C 3-6 cycloalkyl or C 1-6 Alkyl group. In another embodiment, each R b4 Selected independently from C 3-6 cycloalkyl or C 1-4 alkyl.

[0140] In one implementation scheme, each R c4 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 alkyl and phenyl, wherein the C 1-6 Alkyl, phenyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0141] In another implementation, each R c4 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, C 3-6 cycloalkyl and C 1-6 Alkyl, wherein the C 1-6 Alkyl and C 3-6The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl group. In another embodiment, each R c4 Independently selected from hydrogen or C 1-6 alkyl.

[0142] In one implementation scheme, each R d4 Independently selectable hydrogen and C 3-6 cycloalkyl and C 1-6 The group consisting of alkyl groups, wherein the C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl group. In another embodiment, each R d4 Independently selected from hydrogen or C 1-6 alkyl.

[0143] In one implementation scheme, each R e4 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 alkyl and phenyl, wherein the C 1-6 Alkyl, phenyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0144] In another implementation, each R e4 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, C 3-6 cycloalkyl and C 1-6 Alkyl, wherein the C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl group. In another embodiment, each R e4 Independently selected from hydrogen or C 1-6 alkyl.

[0145] In one implementation, R d4 and R e4 When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f4 replace.

[0146] In another implementation, R d4 and R e4 When attached to the same atom, they form a 5-7 membered ring together with the atom to which they are attached, the 5-7 membered ring optionally containing one or more heteroatoms selected from O, N, and S, and wherein the ring is optionally surrounded by one or more R atoms. f4 replace.

[0147] In one implementation, R f4 Choose from the following groups: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 1-6 Alkyl and -OC 1-6 Alkyl group. In another embodiment, R f3 Selected from hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-4 Alkyl, -N(C) 1-4 Alkyl)2, C1-4 Haloalkyl, C 1-4 Alkyl and -OC 1-4 alkyl.

[0148] In one implementation, z1 is an integer selected from 0, 1, and 2. In another implementation, z1 is 1. In yet another implementation, z1 is 0.

[0149] In one embodiment, V comprises one or more functional groups that facilitate covalent bonding with the linker portion L. Examples of suitable functional groups include, for example, amino, amide, carbonyl, sulfonyl, and sulfonylamino.

[0150] In one embodiment, V is selected from the group consisting of: -NH-, -C(O)-, -S(O)2-, -C(O)N(H)-, -N(H)C(O)-, -S(O)(NH)-, -N(H)S(O)-, -S(O)N(H)-, -N(H)S(O)2- and -S(O)2N(H)-.

[0151] In another implementation, V is selected from the group consisting of: -NH-, -C(O)-, -C(O)N(H)- and -N(H)C(O)-.

[0152] In another implementation, V is selected from the group consisting of: -NH-, -C(O)N(H)- and -N(H)C(O)-.

[0153] In another implementation, V is -NH-.

[0154] In one implementation, Q 1 With sub-Q 1a : (Q 1a ) in R 2a It is hydrogen or methyl; X 1 X 3 and X 4 Independently selected from N, CH or CR 4 ; X 6 Selected from N or C; X 7 Selected from O, S, N, CH, CR 4 and NR 4 ; X 9 and X 10 Independently selected from N and CR 3 Or CH; and Where R 1 R 3 and R 4 It is as defined in any of the implementation schemes mentioned above.

[0155] In one implementation, X 6 It is N and X 7 It is CH. In another implementation, X 6 It is N, X 7 It is CH and X 9 It is N. In another implementation, X 6 It is N, X 7 It is CH, X 9 It is N and X 10 Is it CH or CR? 3 , where R 3 It is as defined in any of the implementation schemes mentioned above.

[0156] In another implementation, X 6 It is C and X 7 It is S. In another implementation, X 6 It is C, X 7 It is S and X 9 It is N. In another implementation, X 6 It is C, X 7 It is S, X 9 It is N and X 10 Is it CH or CR? 3 , where R 3 It is as defined in any of the implementation schemes mentioned above.

[0157] In another implementation, R 2a It is hydrogen.

[0158] In one implementation, X 10 Is it CH or CR? 3 .

[0159] In one implementation, R 2a It is methyl, and X 10 It is CH.

[0160] In another implementation, R 2a It is H and X 10 It is CR 3 Appropriately R 3 It is methyl or ethyl.

[0161] In one implementation, Q 1 With sub-Q 1b : (Q1b ) Where R 1 R 2a and R 3 Defined independently based on any of the implementation schemes mentioned above.

[0162] In one implementation, R 2a It is hydrogen. In one implementation, R 3 It is methyl. In another embodiment, R 2a It is hydrogen and R 3 It is a methyl group.

[0163] In one implementation, Q 1 With sub-Q 1c : (Q 1c ) in X 3 X 10 R 1 R 2a and R 3 Defined independently based on any of the implementation schemes mentioned above.

[0164] In one implementation, X 3 It is N.

[0165] In another implementation, X 3 It is CH.

[0166] In one implementation, X 10 Is it CH or CR? 3 .

[0167] In one implementation, R 2a It is methyl, and X 10 It is CH.

[0168] In another implementation, R 2a It is H and X 10 It is CR 3 Appropriately R 3 It is methyl or ethyl.

[0169] In one implementation, Q 1 With sub-Q 1d : (Q 1d ) in X 9 and X 10 Independently selected from N and CR 3 Or CH; X 7a It is CH or N; X 1 Selected from N, CH or CR 4 ;and R 1 R 2a R 3 and R 4 Defined independently based on any of the implementation schemes mentioned above.

[0170] In one implementation, X 9 It is CH or N.

[0171] In one implementation, X 10 Is it CH or CR? 3 .

[0172] In one implementation, X 7a It is CH.

[0173] In one implementation, X 1 Selected from N or CH.

[0174] In one implementation, X 7a It is CH and X 1 It is N. In another implementation, X 7a It is N and X 1 It is CH. In another implementation, X 7a It is CH and X 1 It is CH.

[0175] In one implementation, R 2a It is methyl, and X 10 It is CH.

[0176] In another implementation, R 2a It is H and X 10 It is CR 3 Appropriately R 3 It is methyl or ethyl.

[0177] In one implementation, Q 1d It has the following formula: ;or .

[0178] In one implementation, Q is the formula Q 2 Protein-binding portion: (Q 2 ).

[0179] In one implementation, R 1 A, R 4 And V according to Q 1 Each of the above-mentioned implementation schemes is defined independently.

[0180] In one embodiment, C is a 5- to 12-membered heterocycle containing at least one nitrogen atom in the ring, and wherein -COOR 1 Part of it is bonded to the ring C via nitrogen atoms in the ring C. Therefore, the bonded nitrogen in the ring C and -COOR 1 Partially combined to obtain the carbamate moiety.

[0181] In another embodiment, C is an 8- to 12-membered heterocycle containing at least one nitrogen atom in the ring, and wherein -COOR 1 Partially via a nitrogen atom in ring C bonded to ring C. In another embodiment, C is a 9- or 10-membered heterocycle containing at least one nitrogen atom in the ring, and wherein -COOR 1 Part of it is bonded to the ring C via nitrogen atoms in the ring C.

[0182] In one embodiment, C is an 8- to 11-membered fused bicyclic heterocycle containing at least one nitrogen atom in the ring, and wherein -COOR 1 Partially via nitrogen atoms in ring C bonded to ring C. In another embodiment, C is a 9- or 10-membered fused bicyclic heterocycle containing at least one nitrogen atom in the ring, and wherein -COOR 1 Part of it is bonded to the ring C via nitrogen atoms in the ring C.

[0183] In one implementation, C has the formula C1: (C1) in Dashed line indicates -COOR 1 Attachment point; X 12 X 13 and X 14 Independently selected from N and CR 9 Or CH; X 15 It is CH2, CHR 9 C(R) 9 2. NH, NR 9 S, S(O), S(O)2 or O; and n C It is an integer selected from 0, 1, or 2.

[0184] In one implementation, X 15 Is it O, CH2, or NMe? In one implementation, X 14 It is N.

[0185] In one implementation, X 12 and X 13 It is CH. In another implementation, X 12 and X 13 It is CH and X 14 It is N.

[0186] In one implementation, n C It is an integer selected from 0 or 1.

[0187] In one implementation, n C It is 1 and X 15 It is O, CH2, or NMe. In another implementation, n C It is 1 and X 15 It is O, CH2 or NMe and X 14 It is N. In another implementation, n C It is 1 and X 15 Is it O, CH2, or NMe, X 12 and X 13 It is CH and X 14 It is N.

[0188] In one implementation, n C It is 0 and X 15 It is CH2. In another implementation, n C It is 0 and X 15 It is CH2, and X 14 It is N. In another implementation, n C It is 0 and X 15 It is CH2, X 12 and X 13 It is CH and X 14 It is N.

[0189] In one implementation, C is selected from: Each of them can be arbitrarily assigned to R 9 replace.

[0190] In another implementation, C is selected from: Each of them can be arbitrarily assigned to R 9 replace.

[0191] In another implementation, C is selected from: , Each of them can be arbitrarily assigned to R 9 replace.

[0192] In another implementation, C is selected from: , Each of them can be arbitrarily assigned to R 9 replace.

[0193] In one implementation, R 9 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cycloalkyl, -C(=O)R b3 -C(=O)OR c3 -C(=O)NR d3 R e3 -NR d3 R e3 -NR d3 C(=O)R b3 -OR c3 -SR c3 Wherein C 1-6 Alkyl, OC 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0194] In another implementation, R 9 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -NR d3 R e3 -OR c3 -SR c3 Wherein C 1-6Alkyl, OC 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0195] In another implementation, R 9 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -NR d3 R e3 Wherein C 1-6 Alkyl and OC 1-6 The alkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0196] In another implementation, R 9 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0197] In another implementation, R 9 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 1-4Alkyl, OC 1-4 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0198] In another implementation, R 9 Choose from the group consisting of: hydroxyl, =O, Cl, Br, CN, CF3, OCF3, methyl, ethyl, and OMe.

[0199] In another implementation, R 9 Choose from the group consisting of: hydroxyl, =O, methyl, ethyl, and OMe.

[0200] In one implementation, y2 is an integer selected from 0, 1, and 2. In another implementation, y2 is 1. In yet another implementation, y2 is 0.

[0201] In one implementation, z2 is an integer selected from 0, 1, and 2. In another implementation, z2 is 1. In yet another implementation, z2 is 0.

[0202] In one implementation, Q 2 With sub-Q 2a : (Q 2a ) in X 1 X 3 and X 4 Independently selected from N, CH or CR 4 ; X 6 Selected from N or C; X 7 Selected from O, S, N, CH, CR 4 and NR 4 ; X 15 Selected from CH2, CHR 9 C(R) 9 2. NH, NR 9 S, S(O), S(O)2 or O; and Where R 1 R 9 and R 4 It is as defined in any of the implementation schemes mentioned above.

[0203] In one implementation, X 6 It is N and X 7 It is CH. In another implementation, X 6 It is N, X7 It is CH and X 15 It is O, NMe, or CH.

[0204] In another implementation, X 6 It is C and X 7 It is S. In another implementation, X 6 It is C, X 7 It is S and X 15 It is O, NMe, or CH.

[0205] In another implementation, X 1 X 3 and X 4 Is it CH or CR? 4 , where R 4 It is as defined in any of the implementation schemes mentioned above.

[0206] In another implementation, X 15 Selected from O, NMe, or CH.

[0207] In one implementation, Q 2 With sub-Q 2b : (Q 2b ) in X 1 X 3 and X 4 Independently selected from N, CH or CR 4 ; X 6 Selected from N or C; X 7 Selected from O, S, N, CH, CR 4 and NR 4 ;and Where R 1 and R 4 It is as defined in any of the implementation schemes mentioned above.

[0208] In one implementation, X 6 It is N and X 7 It is CH.

[0209] In another implementation, X 1 X 3 and X 4 Is it CH or CR? 4 .

[0210] In another implementation, X 6 It is C and X 7 It is S.

[0211] In another implementation, Q 2 With sub-Q 2c : (Q 2c ) Where X 15 Selected from CH2, CHR 9 C(R) 9 2. NH, NR 9 S, S(O), S(O)2 or O; and Where R 1 It is as defined in any of the implementation schemes mentioned above.

[0212] In one implementation, X 15 Selected from O, NMe, or CH.

[0213] In one implementation, Q 2 With sub-Q 2d : (Q 2d ) Where R 1 It is as defined in any of the implementation schemes mentioned above.

[0214] In another implementation, Q 2 With sub-Q 2e : (Q 2e ) Where X 15 Selected from CH2, CHR 9 C(R) 9 2. NH, NR 9 S, S(O), S(O)2 or O; X 7b Selected from CH or N; and X 1 Selected from N, CH or CR 4 ; R 4 and R 1 It is as defined in any of the implementation schemes mentioned above.

[0215] In one implementation, X 15 Selected from O, NMe, or CH.

[0216] In one implementation, X 1 Selected from N or CH.

[0217] In one implementation, X7b Selected from CH.

[0218] In one implementation, Q 2 With sub-Q 2f : (Q 2f ) Where X 1 Selected from N, CH or CR 4 And X 7b Selected from CH or N.

[0219] R 4 and R 1 It is as defined in any of the implementation schemes mentioned above.

[0220] In one implementation, X 1 Selected from N, CH or CR 4 And X 7b It is CH.

[0221] In one implementation, X 1 Selected from N or CH, and X 7b It is CH.

[0222] In one implementation, X 7b It is CH and X 1 It is N. In another implementation, X 7b It is N and X 1 It is CH. In another implementation, X 7b It is CH and X 1 It is CH.

[0223] Connector part L The linker is used to link the protein targeting region Q to the E3 ubiquitin ligase binding region M.

[0224] In one embodiment, L comprises one or more atoms that covalently link the protein-targeting portion Q to the E3 ubiquitin-ligase-binding portion M. In one embodiment, L is a linear portion. In another embodiment, L is a branched portion.

[0225] In one embodiment, L comprises one or more functional groups, particularly at the end of the portion that can facilitate covalent bonding with the protein-targeting portion Q and / or the E3 ubiquitin ligase-binding portion M. Examples of suitable functional groups include, for example, amino, amide, carbonyl, ether, ester, thioether, sulfonyl, and sulfonamide.

[0226] In one embodiment, the group at either end of the linker is derived from a group that can react with the protein-targeting portion Q and / or the E3 ubiquitin-binding portion M to form a bond. The reactive group may be selected from, but is not limited to, groups that will directly react with other reactive groups on the protein-targeting portion Q and / or the E3 ubiquitin-binding portion M. The reaction of this reactive group with a reactive group on the precursor of the protein-targeting portion Q and / or the E3 ubiquitin-binding portion M can generate a functional group in the linker adjacent to the protein-targeting portion Q and / or the E3 ubiquitin-binding portion M, which may be referred to herein as a “bonding moiety”.

[0227] Suitablely, the linker portion comprises two or more bonded portions and one or more spacer portions. The spacer portions can be varied to control the separation between the protein-targeting portion Q and / or the E3 ubiquitin-binding portion M. The spacer portions can contain aliphatic or polymeric chains, such as polyethylene glycol (PEG) chains, or cyclic groups or components thereof. Functional groups may also be present within the spacer portions, for example, to influence the physical properties of the entire compound, such as solubility, permeability, and pharmacokinetic properties.

[0228] The length of the ligand can be varied to avoid spatial interactions between the protein-targeting portion Q and / or the E3 ubiquitin ligase-binding portion M, and to allow the protein-targeting portion to interact effectively with its protein target.

[0229] The linker is suitably designed to maintain the connection between the protein-targeting portion Q and / or the E3 ubiquitin-binding portion M for an appropriate duration under physiological conditions. However, the linker group can be cleavable, for example, under non-physiological conditions.

[0230] Technicians will understand that the constituent groups of the connecting parts, such as L a L b1 L b2 L c L d1 and L d2 It bonds to two or more other atoms or groups. Suitablely, the linking portion is divalent.

[0231] In one implementation, L is the connecting part of formula L1: L appears each time a Independently selected from -S-, -S(=O)-, -S(=O)2-, -O-, -C(=O-), -C(=O)O-, -OC(=O-), -CR 5 R 6 -、-CR 5 =CR6 -、-C≡C-、-NR 5 -、-NR 5 C(=O)-、-C(=O)NR 5 -、-OC(=O)NR 5 -、-NR 5 C(=O)NR 6 -、-NR 5 C(=O)O-、-NR 5 S(O)NR 6 -、-OC(R 5 (R) 6 )C(R 5 (R) 6 )-、-S(=O)2NR 5 -、-NR 5 S(=O)2-、C3-C 13 cycloalkyl, C6-C 11 aryl, 5- to 11-membered heteroaryl and 3- to 11-membered heterocycloalkyl, wherein the C3-C 13 cycloalkyl, C6-C 11 aryl, 5- to 11-membered heteroaryl and 3- to 11-membered heterocyclic alkyl groups are optionally separated by one or more R groups. 7 replace; n1 is a value from 1 to 50; and R 5 R 6 and R 7 Each time it appears, independently select the group consisting of the following items: hydrogen, hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups, phenyl groups, 5-6-membered heteroaryl groups, 3- to 7-membered heterocyclic alkyl groups, and C 3-6 Cycloalkyl groups, each of which may optionally be substituted with one or more groups selected from the following: C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, phenyl, and hydroxyl.

[0232] In one implementation, n1 is a value from 1 to 40, or from 1 to 30, or from 1 to 20, or from 1 to 15, or from 1 to 10.

[0233] In another implementation, n1 is a value of 3 to 40, or 3 to 30, or 3 to 20, or 3 to 15, or 3 to 10.

[0234] In another implementation, n1 is a value of 5 to 40, or 5 to 30, or 5 to 20, or 5 to 15, or 5 to 10.

[0235] In one implementation, each L a Independently selected from -S-, -S(=O)-, -S(=O)2-, -O-, -C(=O)-, -CR 5 R 6 -、-NR 5 -、-NR 5 C(=O)-、-C(=O)NR 5 -、-OC(R 5 (R) 6 )C(R 5 (R) 6 )-、-S(=O)2NR 5 -、-NR 5 S(=O)2-、C3-C 13 cycloalkyl, C6-C 11 aryl, 5- to 11-membered heteroaryl and 3- to 11-membered heterocycloalkyl, wherein the C3-C 13 cycloalkyl, C6-C 11 aryl, 5- to 11-membered heteroaryl and 3- to 11-membered heterocyclic alkyl groups are optionally separated by one or more R groups. 7 replace.

[0236] In another implementation, each L a Independently selected from -O-, -C(=O)-, -CR 5 R 6 -、-NR 5 -、-NR 5 C(=O)-、-C(=O)NR 5 -、-OC(R 5 (R) 6 )C(R 5 (R) 6 )-、C3-C 13 cycloalkyl, C6-C 11 aryl, 5- to 11-membered heteroaryl and 3- to 11-membered heterocycloalkyl, wherein the C3-C 13 cycloalkyl, C6-C 11 aryl, 5- to 11-membered heteroaryl and 3- to 11-membered heterocyclic alkyl groups are optionally separated by one or more R groups. 7 replace.

[0237] In another implementation, each L a Independently selected from -O-, -C(=O)-, -CR 5 R 6 -、-NR 5 -、-NR 5 C(=O)-、-C(=O)NR5 -、-OC(R 5 (R) 6 )C(R 5 (R) 6 )-、C3-C 13 Cycloalkyl, 5- to 11-membered heteroaryl and 3- to 11-membered heterocycloalkyl, wherein the C3-C 13 cycloalkyl, C6-C 11 aryl, 5- to 11-membered heteroaryl and 3- to 11-membered heterocyclic alkyl groups are optionally separated by one or more R groups. 7 replace.

[0238] In another implementation, each L a Yes -CR 5 R 6 -, appropriately, -CH2-. In another implementation, each L a Yes -CR 5 R 6 -, appropriately, -CH2-, and n1 is a value of 1, 2, 3, 4, 5, 6, 7 or 8.

[0239] In one implementation, L is the connecting part of formula L2: in L b1 and L b2 Independently does not exist or is freely chosen -C(=O)-, -NR 5 C(=O)- and -C(=O)NR 5 -A group; L d1 and L d2 Independently does not exist or is chosen freely from C3-C 13 The group consisting of cycloalkyl, phenyl, 5- to 6-membered heteroaryl and 3- to 10-membered heterocycloalkyl, wherein the C3-C 13 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl and 3- to 10-membered heterocycloalkyl are optionally separated by one or more R 7 replace.

[0240] Each L c Independently select from the following groups: -CR 5 R 6 -、-O-、-OC(R 5 (R) 6 )C(R 5 (R) 6 -, -C(=O)-, -NR 5 -、-NR 5 C(=O)-、-C(=O)NR5 - 5-6-membered heteroaryl and 5-6-membered heterocyclic alkyl, wherein the 5-6-membered heteroaryl and 5-6-membered heterocyclic alkyl are optionally represented by one or more R 7 replace; n2 is a value between 0 and 20; and R 5 R 6 and R 7 Each time it appears, independently select the group consisting of the following items: hydrogen, hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups, phenyl groups, 5-6-membered heteroaryl groups, 3- to 7-membered heterocyclic alkyl groups, and C 3-6 Cycloalkyl groups, each of which may optionally be substituted with one or more groups selected from the following: C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, phenyl, and hydroxyl.

[0241] In one implementation, L b1 It is the binding portion to the protein-binding site Q. In another embodiment, L b1 It is the binding part of M, which is the binding site of E3 ubiquitin ligase.

[0242] In one implementation, L b1 and L b2 It either does not exist independently or is -C (=O)-. In another implementation, L b1 It does not exist and L b2 It is -C(=O)-. In another implementation, L b1 It is -C(=O)- and L b2 It does not exist. In another implementation, L b1 and L b2 Both are -C(=O)-.

[0243] In one implementation, L d1 and L d2 Independently does not exist or is selected freely from C5-C 10 The group consisting of cycloalkyl, phenyl, 5- to 6-membered heteroaryl and 5- to 10-membered heterocycloalkyl, wherein the C5-C 10 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl and 5- to 10-membered heterocycloalkyl are optionally separated by one or more R 7 replace.

[0244] In one implementation, L d1 and L d2Independently absent or selected from the group consisting of C5-C8 cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 5- to 8-membered heterocycloalkyl, wherein the C5-C8 cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 5- to 8-membered heterocycloalkyl are optionally represented by one or more R 7 replace.

[0245] In one implementation, L d1 The group consisting of C5-C8 cycloalkyl, phenyl, and 5- to 8-membered heterocyclic alkyl groups is absent or selected from the group consisting of C5-C8 cycloalkyl, phenylene, and 5- to 8-membered heterocyclic alkyl groups, wherein the C5-C8 cycloalkyl, phenylene, and 5- to 8-membered heterocyclic alkyl groups are optionally represented by one or more R groups. 7 replace.

[0246] In one implementation, L d2 The group consisting of C5-C8 cycloalkyl, 5- to 6-membered heteroaryl, and 5- to 8-membered heterocycloalkyl is absent or selected from the group consisting of C5-C8 cycloalkyl, 5- to 6-membered heteroaryl, and 5- to 8-membered heterocycloalkyl, wherein the C5- to 8-membered cycloalkyl, 5- to 6-membered heteroaryl, and 5- to 8-membered heterocycloalkyl are optionally represented by one or more R 7 replace.

[0247] In one implementation, L d1 It does not exist and L d2 Selected from the group consisting of C5-C8 cycloalkyl, phenylene, 5- to 6-membered heteroaryl, and 5- to 8-membered heterocycloalkyl, wherein the C5- to C8 cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 5- to 8-membered heterocycloalkyl are optionally separated by one or more R 7 replace.

[0248] In another implementation, L d1 Selected from the group consisting of phenylene and 5- to 8-membered heterocyclic alkyl groups, wherein the phenylene and the 5- to 8-membered heterocyclic alkyl groups are optionally separated by one or more R groups. 7 Replace; and L d2 It does not exist.

[0249] In another implementation, L d1 It does not exist and L d2 It is optional to be controlled by one or more R 7 Replaced 5- to 6-membered heteroaryl groups.

[0250] In one implementation, L d1 and L d2 Independently selected from the group consisting of C5-C8 cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 5- to 8-membered heterocycloalkyl, wherein the C5- to C8 cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 5- to 8-membered heterocycloalkyl are optionally represented by one or more R 7 replace.

[0251] In one implementation, Ld1 and L d2 Neither of them exists.

[0252] In one implementation, each L c Independently select from the following groups: -CR 5 R 6 -、-O-、-OC(R 5 (R) 6 )C(R 5 (R) 6 -, -C(=O)-, -NR 5 -、-NR 5 C(=O)-、-C(=O)NR 5 - and 5-6 membered heterocyclic alkyl groups, wherein the 5-6 membered heterocyclic alkyl group is optionally composed of one or more R groups. 7 replace.

[0253] In another implementation, each L c Independently select from the following groups: -CR 5 R 6 -、-O-、-OC(R 5 (R) 6 )C(R 5 (R) 6 -, -C(=O)-, -NR 5 - and 5-6 membered heterocyclic alkyl groups, wherein the 5-6 membered heterocyclic alkyl group is optionally composed of one or more R groups. 7 replace.

[0254] In another implementation, each L c Independent choice of freedom - CR 5 R 6 -、-O-、-OC(R 5 (R) 6 )C(R 5 (R) 6 The group consisting of 5- and 6-membered heterocyclic alkyl groups, wherein the 5- and 6-membered heterocyclic alkyl groups are optionally separated by one or more R groups. 7 replace.

[0255] In another implementation, each L c Independently selected from the group consisting of -CH2-, -O-, -OCH2CH2- and 5-6-membered heterocyclic alkyl groups, wherein the 5-6-membered heterocyclic alkyl group is optionally separated by one or more R groups. 7 replace.

[0256] In another implementation, each L c Choose independently the group consisting of -CH2-, -O-, and -OCH2CH2-.

[0257] In one embodiment, n2 is a value from 1 to 20. In another embodiment, n2 is a value from 2 to 20. In another embodiment, n2 is a value from 3 to 20. In another embodiment, n2 is a value from 4 to 20. In another embodiment, n2 is a value from 3 to 20. In another embodiment, n2 is a value from 5 to 20.

[0258] In one embodiment, n2 is a value from 0 to 15. In another embodiment, n2 is a value from 0 to 12. In another embodiment, n2 is a value from 0 to 11. In yet another embodiment, n2 is a value from 0 to 10.

[0259] In one embodiment, n2 is a value from 1 to 15. In another embodiment, n2 is a value from 1 to 12. In yet another embodiment, n2 is a value from 1 to 11. In still another embodiment, n2 is a value from 1 to 10.

[0260] In one embodiment, n2 is a value from 2 to 15. In another embodiment, n2 is a value from 2 to 12. In yet another embodiment, n2 is a value from 2 to 11. In still another embodiment, n2 is a value from 2 to 10.

[0261] In one embodiment, n2 is a value from 4 to 15. In another embodiment, n2 is a value from 4 to 12. In yet another embodiment, n2 is a value from 4 to 11. In still another embodiment, n2 is a value from 4 to 10.

[0262] In one implementation, R 5 Each time it appears, it is either hydrogen or a group selected from the following: hydrogen, C 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl, phenyl and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0263] In one implementation, R 5 Each time it appears, it is independently either hydrogen or C. 1-4 Alkyl group. Suitablely, R 5 It is hydrogen or methyl. Appropriately, R 5 It is hydrogen.

[0264] In one implementation, R 6 Each time it appears, it is either hydrogen or a group selected from the following: hydrogen, C 1-4Alkyl, C 1-4 alkenyl, C 2-4 alkynyl, phenyl and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0265] In one implementation, R 6 Each time it appears, it is independently either hydrogen or C. 1-4 Alkyl group. Suitablely, R 6 It is hydrogen or methyl. Appropriately, R 6 It is hydrogen.

[0266] In one implementation, R 7 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0267] In another implementation, R 7 Each time it appears, it is independently selected from hydroxyl, =O, and C. 1-4 A group composed of alkyl groups.

[0268] In one implementation, L is the connecting part of formula L3: (L3), Where n4 is an integer value from 0 to 20.

[0269] In one implementation, n4 is a value from 2 to 20, and appropriately a value from 3 to 20.

[0270] In one implementation, n4 is a value from 1 to 15, preferably from 1 to 12, preferably from 1 to 10, preferably from 3 to 10.

[0271] In one implementation, n4 is 4, 5, 6, 7, 8, 9, or 10.

[0272] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0273] In one implementation, L is the connecting part of formula L4: (L4), Where n4a is an integer value from 0 to 20.

[0274] In one implementation, n4a is a value from 2 to 20, and suitably from 3 to 20.

[0275] In one implementation, n4a is a value from 1 to 15, preferably from 1 to 12, preferably from 1 to 10, preferably from 3 to 10.

[0276] In one implementation, n4a is 4, 5, 6, 7, 8, 9, or 10.

[0277] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0278] In one implementation, L is the connecting part of formula L5: (L5), Where n3 is a value from 1 to 10, and each n5 is an independent integer value from 0 to 5.

[0279] In one embodiment, n3 is a value from 2 to 8, preferably 3 to 8, preferably 4 to 8. In another embodiment, n3 is a value from 3 to 6, preferably 3 to 5, preferably 4 or 5.

[0280] In one implementation, n5 is a value from 0 to 3, preferably from 0 to 2, preferably 0 or 1. In another implementation, n5 is a value of 1, 2 or 3, preferably 1 or 2.

[0281] In another implementation, n3 is a value from 3 to 6, and each n5 is independently 0, 1, or 2.

[0282] In one embodiment, L is the connecting portion of formula L5, and the connecting portion is selected from: ; ;and .

[0283] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0284] In one implementation, L is the connecting portion of formula L6: (L6), Where n3 is a value from 1 to 10, and each n5 is an independent integer value from 0 to 5.

[0285] In one implementation, n3 and n5 are according to any of the implementations mentioned above.

[0286] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0287] In one implementation, L is the connecting portion of formula L7: (L7), Where n12 is a value from 2 to 10; In one implementation, n12 is a value of 2 to 8, preferably 2 to 5, preferably 2, 3 or 4.

[0288] In one embodiment, L is the connecting portion of formula L7, and the connecting portion is selected from: ; .

[0289] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0290] In one implementation, L is the connecting portion of formula L8: (L8), Where n6 is an integer value from 0 to 10, n7 is a value from 1 to 12; n19 is an integer value of 0 or 1; and the ring D is optionally bounded by one or more R... 7 Substituted phenyl or 6-membered heteroaryl ring.

[0291] In one implementation, L is the connecting portion of formula L8a: (L8a) Where n6 is an integer value from 0 to 10, n7 is a value from 1 to 12; n19 is an integer value of 0 or 1; and the ring D is optionally bounded by one or more R... 7 Substituted phenyl or 6-membered heteroaryl ring.

[0292] In one implementation, L is the connecting portion of formula L8b: (L8b) Where n6 is an integer value from 0 to 10, n7 is a value from 1 to 12; n19 is an integer value of 0 or 1; and the ring D is optionally bounded by one or more R... 7 Substituted phenyl or 6-membered heteroaryl ring.

[0293] In one implementation, n6 is an integer value from 0 to 5, preferably 0 and 3, preferably 0, 1, or 2.

[0294] In one implementation, n7 is a value from 1 to 12, preferably from 1 to 8, preferably from 1 to 6.

[0295] In one implementation, n7 is 4, 5, or 6 and n6 is 0. In another implementation, n7 is 1 and n6 is 2 or 3.

[0296] In one embodiment, D is phenyl or pyridyl.

[0297] In one embodiment, D is phenyl, n7 is 1, and n6 is 2 or 3. In another embodiment, D is pyridyl, n7 is 4, 5, or 6, and n6 is 0.

[0298] In one embodiment, L is the connecting portion of formula L8, and the connecting portion is selected from: ; ; ; ; ; ; ;or .

[0299] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0300] In one implementation, R 7 It is as defined in any of the implementation schemes mentioned above.

[0301] In one implementation, L is the connecting portion of formula L9: (L9), Where n8 is a value from 1 to 12.

[0302] In one implementation, n8 is a value of 3 to 10, preferably 4 to 6.

[0303] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0304] In one implementation, L is the connecting portion of formula L10: (L10), Where n11 is an integer value from 0 to 12, and the ring E is optionally bounded by one or more R... 7 Substituted phenyl or 6-membered heteroaryl ring.

[0305] In one implementation, L is the connecting portion of formula L10a: (L10a), Where n11 is an integer value from 0 to 12, and the ring E is optionally bounded by one or more R... 7 Substituted phenyl or 6-membered heteroaryl ring.

[0306] In another embodiment, L is the connecting portion of formula L10b: (L10b), Where n11 is an integer value from 0 to 12, and the ring E is optionally bounded by one or more R... 7 Substituted phenyl or 6-membered heteroaryl ring.

[0307] In one implementation, n11 is a value from 1 to 12, preferably from 3 to 12, preferably from 3 to 10, preferably from 3 to 8.

[0308] In one embodiment, ring E is phenyl, pyridyl, or pyridone.

[0309] In one embodiment, E is pyridone and n11 is 5, 6 or 7.

[0310] In one embodiment, L is the connecting portion of formula L10, and the connecting portion is selected from: ; .

[0311] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0312] In one implementation, L is the connecting portion of formula L11: (L11) Each of n12 and n13 is an independent integer value from 0 to 5, and the ring F is optionally bounded by one or more R... 7 Substituted 5- or 6-membered heterocyclic alkyl rings.

[0313] In one implementation, each n12 is independently a value from 1 to 5, preferably from 1 to 3, preferably 1 or 2.

[0314] In one implementation, each n12 is an independent integer value from 0 to 3, preferably 0, 1, or 2.

[0315] In one embodiment, ring F is a 6-membered heterocyclic alkyl ring, suitably selected from piperazine or piperidinyl.

[0316] In one embodiment, the connecting portion has formula L11a: (L11a); Where ring K1 can be arbitrarily divided by one or more R... 24 Substituted 5- to 10-membered heterocyclic alkyl rings; n40 is an integer value from 0 to 8; n41 is an integer value from 0 to 8; R 24 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0317] In one implementation, ring K1 is optionally bounded by one or more R... 24 The substituted 5- to 9-membered heterocyclic alkyl ring suitably contains one or two nitrogen atoms. In one embodiment, ring K1 is optionally separated by one or more R atoms. 24 The substituted 5- or 6-membered heterocyclic alkyl ring suitably contains one or two nitrogen atoms. Suitably, K1 is optionally surrounded by one or more R atoms. 24 Substituted piperidinyl ring or piperazine ring.

[0318] In one embodiment, n40 is a value from 1 to 8, preferably from 1 to 6. In another embodiment, n40 is a value of 1, 2, or 3, preferably 1 or 2, preferably 1.

[0319] In one embodiment, n41 is a value from 1 to 8, preferably from 1 to 6. In another embodiment, n41 is a value of 1, 2, or 3, preferably 1 or 2, preferably 1.

[0320] In one implementation, R 24 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0321] In another implementation, R 24 Each time it appears, it is independently selected from hydroxyl, =O, and C. 1-4 A group composed of alkyl groups.

[0322] In one embodiment, the connecting portion of formula L11 or formula L11a is: .

[0323] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0324] In one embodiment, the connecting portion has formula L11b: (L11b); Where ring K2 can be arbitrarily divided by one or more R... 25 Substituted 5- to 10-membered heterocyclic alkyl rings; n42 is an integer value from 0 to 8; n43 is an integer value from 0 to 8; n44 and n45 are independently selected from integer values ​​0 to 5; and R 25 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0325] In one implementation, ring K2 is optionally bounded by one or more R... 25 The substituted 5- to 9-membered heterocyclic alkyl ring suitably contains one or two nitrogen atoms. In one embodiment, ring K2 is optionally separated by one or more R atoms. 25 The substituted 5- or 6-membered heterocyclic alkyl ring suitably contains one or two nitrogen atoms. Suitably, K2 is optionally surrounded by one or more R atoms. 25 Substituted piperidinyl ring or piperazine ring.

[0326] In one embodiment, n42 is a value from 1 to 8, preferably from 1 to 6. In another embodiment, n42 is a value of 1, 2, or 3, preferably 1 or 2, preferably 1.

[0327] In one embodiment, n43 is a value from 1 to 8, preferably from 1 to 6. In another embodiment, n43 is a value of 1, 2, or 3, preferably 1 or 2, preferably 1.

[0328] In another implementation, n42 is an integer value from 0 to 5, preferably from 0 to 3. In yet another implementation, n42 is an integer value of 0, 1, or 2, preferably 0 or 1.

[0329] In another embodiment, n43 is an integer value from 0 to 5, preferably from 0 to 3. In another embodiment, n43 is an integer value of 0, 1, or 2, preferably 0 or 1.

[0330] In one implementation, n44 and n45 are independently selected from the values ​​1, 2, or 3, preferably 1 or 2, preferably 1.

[0331] In one implementation, R 25 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0332] In another implementation, R 25 Each time it appears, it is independently selected from hydroxyl, =O, and C. 1-4 A group composed of alkyl groups.

[0333] In one embodiment, the connection portion of formula L11b is selected from the following: ; ; ; .

[0334] In one embodiment, the connecting portion has formula L11c: (L11c); Where ring K3 can be arbitrarily divided by one or more R... 27 Substituted 4- to 10-membered heterocyclic alkyl rings; n47 is an integer value from 0 to 3; n48 is selected from integer values ​​0 to 5; n49 is an integer value of 0 or 1; R 12 and R 13 Independently selected from H, halogen, C 1-4 Alkyl, C 3-6 cycloalkyl; or R 12 and R 13 Together with the carbon atoms to which they are attached, they form C 3-6 cycloalkyl groups; and R 27 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0335] In one implementation, ring K3 is optionally bounded by one or more R... 27 The substituted 4- to 9-membered heterocyclic alkyl rings suitably contain one or two nitrogen atoms. In one embodiment, ring K3 is optionally separated by one or more R atoms. 27 The substituted 4- or 6-membered heterocyclic alkyl ring suitably contains one or two nitrogen atoms. Suitably, K3 is optionally surrounded by one or more R atoms. 27 Substituted piperidinyl ring or piperazine ring.

[0336] In one implementation, n48 is selected from integer values ​​0 to 3; suitably 0, 1, or 2. In one implementation, both n47 and n48 are 1.

[0337] In one embodiment, n49 is 1, and n47 and n48 are independently selected from integer values ​​0 to 2. In another embodiment, n49 is 1, and n47 and n48 are independently selected from the value 1 or 2.

[0338] In one implementation, R 12 and R 13 Independently selected from H and C 1-4 Alkyl group. In another embodiment, R 12 and R 13 It is independently selected from H and methyl.

[0339] In one implementation, R 12 and R 13 One of them is H and the other is methyl. In another embodiment, R 12 and R 13 Both are H.

[0340] In one implementation, R 27 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0341] In another implementation, R 27 Each time it appears, it is independently selected from hydroxyl, =O, and C. 1-4 A group composed of alkyl groups.

[0342] In one embodiment, the connection portion of formula L11c is selected from the following: ; ; ; ; ; ; ; ; ; ; ; ; ; .

[0343] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0344] In one implementation, L is the connecting portion of formula L12: (L12) Each n14 and n15 is independently an integer value from 0 to 5, and ring G and ring H are independently selected from the group consisting of: 5- to 7-membered heterocyclic alkyl, 5- or 6-membered heteroaryl, and C3-C. 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 7 replace.

[0345] In one implementation, n14 and n15 are independently integer values ​​of 0, 1, 2, or 3. In one implementation, n14 is 0 and n15 is 0 or 1. In another implementation, n14 is 2 and n15 is 2.

[0346] In one embodiment, cycloG is selected from the group consisting of: 5- to 7-membered heterocyclic alkyl groups and C3-C4 groups. 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 7 replace.

[0347] In one implementation, the ring H can optionally be composed of one or more Rs. 7 Replaced 5- to 6-membered heteroaryl groups.

[0348] In one embodiment, the connection portion of formula L12 is selected from the following: ; ; .

[0349] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0350] In one implementation, L is a connection portion selected from the following: ; ; ; ; ; ;or .

[0351] In one implementation, L is the connecting portion of formula L13: (L13); Where n16 is an integer value of 0 or 1, and n17 is a value from 1 to 12.

[0352] In one implementation, n17 is a value from 1 to 10, preferably from 1 to 7, preferably from 3 to 5.

[0353] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0354] In one implementation, L is the connecting portion of formula L14a: (L14a); Where n18 is a number from 1 to 5, and ring G1 and ring H1 are independently selected from the group consisting of: 5- to 7-membered heterocyclic alkyl, 5- or 6-membered heteroaryl, and C3-C 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 7 replace.

[0355] In one implementation, n18 is a value of 1, 2, or 3.

[0356] In one embodiment, cycloG1 is selected from the group consisting of: 5- to 7-membered heterocyclic alkyl groups and C3-C4 groups. 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 7 replace.

[0357] In one implementation, ring H1 can optionally be divided by one or more R... 7 Replacement of 5- or 6-membered heteroaryl groups.

[0358] In one embodiment, the connection portion of formula L14a is selected from the following: ; ; ; ; .

[0359] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0360] In one implementation, L is the connecting portion of formula L14b: (L14b); Where n20 is a value from 1 to 5; Where n21 and n27 are independent integer values ​​0 or 1; The ring G2 and ring H2 are independently selected from the group consisting of: 4- to 10-membered heterocyclic alkyl groups, 5- or 6-membered heteroaryl groups, and C3-C. 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 8 replace; R 8 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; and R 10 and R 11 Independently selected from H and C 1-4 Alkyl, C 3-6 cycloalkyl; or R 10 and R 11 Together with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups.

[0361] In one embodiment, ring G2 and ring H2 are independently selected from the group consisting of: 5- to 10-membered heterocyclic alkyl groups, 5- or 6-membered heteroaryl groups, and C3-C4 groups. 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 8 replace.

[0362] In one implementation, n27 is 1. In another implementation, n27 is 0.

[0363] In another embodiment, ring G2 and ring H2 are independently selected from the group consisting of: 5- to 10-membered heterocycloalkyl, 5- or 6-membered heteroaryl, and C3-C.10 Cycloalkyl groups, each optionally consisting of one or more R groups. 8 Replace; and n27 is 1.

[0364] In one implementation, ring H2 can optionally be divided by one or more R... 8 Replacement of 5- or 6-membered heteroaryl groups.

[0365] In one implementation, ring H2 can optionally be divided by one or more R... 8 Substituted pyridinyl ring, pyrimidinyl ring, pyridazinyl ring or pyrazinyl ring.

[0366] In one implementation, L is the connecting portion of formula L14b1: (L14b1); In one embodiment, cycloG2 is selected from the group consisting of: 5-membered to 10-membered heterocyclic alkyl groups and C3-C4 groups. 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 8 Replacement. In another embodiment, ring G2 is optionally replaced by one or more R... 8 The substituted 5- to 9-membered heterocyclic alkyl group. In another embodiment, ring G2 is optionally replaced by one or more R groups. 8 The substituted alkyl group is a 5- to 9-membered heterocyclic alkyl group containing one or two nitrogen atoms. In another embodiment, ring G2 is optionally replaced by one or more R atoms. 8 Substituted 5- to 8-membered heterocyclic alkyl groups containing one or two nitrogen atoms.

[0367] In one embodiment, ring G2 is selected from piperazinyl ring, piperidinyl ring, 2,6-diazaspiro[3.3]heptyl ring, octahydropyrrolo[3,4-c]pyrrole ring, 3,6-diazabicyclo[3.1.1]heptane ring, or 2,5-diazabicyclo[2.2.1]heptane ring, each of which may optionally be surrounded by one or more R 8 replace.

[0368] In one implementation, ring G2 is optionally divided by one or more R... 8 Substituted piperazine group.

[0369] In one implementation, n27 is 1.

[0370] In one implementation, L is the connecting portion of formula L14b2: (L14b2); In one implementation, n20 is a value of 1, 2, or 3.

[0371] In one implementation, n21 is 1.

[0372] In one implementation, n27 is 1.

[0373] In another implementation, n21 is 1, n20 is 1 and n27 is 0.

[0374] In one implementation, R 8 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0375] In another implementation, R 8 Each time it appears, it is independently selected from hydroxyl, =O, and C. 1-4 A group composed of alkyl groups.

[0376] In one implementation, R 10 and R 11 Independently selected from H or C 1-3 Alkyl; or R 10 and R 11 Together with the carbon atoms to which they are attached, they form cyclopropyl groups.

[0377] In one implementation, R 10 and R 11 It is independently selected from H or methyl.

[0378] In one embodiment, the connection portion of formula L14b is selected from the following: ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; .

[0379] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0380] In one implementation, L is the connecting portion of formula L14c: (L14c); Where n23 is an integer value of 0 or 1; n24 is an integer value from 0 to 3; The ring G3 and ring H3 are independently selected from the group consisting of: 4- to 10-membered heterocyclic alkyl groups, 5- or 6-membered heteroaryl groups, and C3-C. 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 8c replace; R 8c Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; and R 12c and R 13c Independently selected from H, halogen, C 1-4 Alkyl, C 3-6 cycloalkyl; or R 12c and R 13cTogether with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups.

[0381] In one implementation, ring H3 can optionally be composed of one or more R... 8c Replacement of 5- or 6-membered heteroaryl groups.

[0382] In one implementation, ring H3 can optionally be composed of one or more R... 8c Substituted pyridinyl ring, pyrimidinyl ring, pyridazinyl ring or pyrazinyl ring.

[0383] In one embodiment, cycloG3 is selected from the group consisting of: 4- to 10-membered heterocyclic alkyl groups and C3-C4 groups. 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 8c Replacement. In another embodiment, ring G3 is optionally replaced by one or more R... 8c Substituted 4- to 9-membered heterocyclic alkyl groups. In another embodiment, ring G3 is optionally replaced by one or more R groups. 8c The substituted heterocyclic alkyl group comprises one or two nitrogen atoms and consists of four to nine members. In another embodiment, ring G3 is optionally replaced by one or more R atoms. 8c Substituted 4- to 8-membered heterocyclic alkyl groups containing one or two nitrogen atoms.

[0384] In one implementation, R 12c and R 13c Independently selected from H and C 1-4 Alkyl group. In another embodiment, R 12c and R 13c It is independently selected from H and methyl.

[0385] In one implementation, R 12c and R 13c One of them is H and the other is methyl. In another embodiment, R 12c and R 13c Both are H.

[0386] In one implementation, n23 is 1.

[0387] In one implementation, n24 is 1.

[0388] In another implementation, n23 is 0 and n24 is 2.

[0389] In one implementation, R 8c Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0390] In another implementation, R 8c Each time it appears, it is independently selected from hydroxyl, =O, and C. 1-4 A group composed of alkyl groups.

[0391] In one embodiment, the connection portion of formula L14c is selected from the following: ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0392] In one implementation, L is the connecting portion of formula L14d: (L14d); Where n26 is an integer value of 0 or 1; n28 is an integer value of 0, 1, or 2; Z does not exist or is selected from NH, N(C) 1-3 Alkyl), O, or S groups; The ring G4 and ring H4 are independently selected from the group consisting of: 4- to 10-membered heterocyclic alkyl groups, 5- or 6-membered heteroaryl groups, and C3-C4 groups. 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 8d replace; R 8d Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; R 10d and R 11d Independently selected from H and C 1-4 Alkyl, C 3-6 cycloalkyl; or R 10d and R 11d Together with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups; R 12d and R 13d Independently selected from H, halogen, C 1-4 Alkyl, C 3-6 cycloalkyl; or R 12d and R 13d Together with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups.

[0393] In one implementation, Z is absent or selected from NH, N(C) 1-3 Alkyl) or O groups. In another embodiment, Z is absent or is a group selected from NH or NMe.

[0394] In one implementation, ring H4 can optionally be composed of one or more R... 8d Replacement of 5- or 6-membered heteroaryl groups.

[0395] In one implementation, ring H4 can optionally be composed of one or more R... 8d Substituted pyridinyl ring, pyrimidinyl ring, pyridazinyl ring or pyrazinyl ring.

[0396] In one embodiment, cycloG4 is selected from the group consisting of: 4- to 10-membered heterocyclic alkyl groups and C3-C4 groups. 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 8dReplacement. In another embodiment, ring G4 is optionally replaced by one or more R... 8d Substituted 4- to 9-membered heterocyclic alkyl groups. In another embodiment, ring G4 is optionally replaced by one or more R groups. 8d The substituted heterocyclic alkyl group comprises one or two nitrogen atoms and consists of four to nine members. In another embodiment, ring G4 is optionally replaced by one or more R atoms. 8d Substituted 4- to 8-membered heterocyclic alkyl groups containing one or two nitrogen atoms.

[0397] In one implementation, R 12d and R 13d Independently selected from H and C 1-4 Alkyl group. In another embodiment, R 12d and R 13d It is independently selected from H and methyl.

[0398] In one implementation, R 12d and R 13d One of them is H and the other is methyl. In another embodiment, R 12d and R 13d Both are H.

[0399] In one implementation, n26 is 1.

[0400] In one implementation, n28 is 1. In another implementation, Z does not exist, n26 is 0 and n28 is 2.

[0401] In one implementation, R 8d Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0402] In another implementation, R 8d Each time it appears, it is independently selected from hydroxyl, =O, and C. 1-4 A group composed of alkyl groups.

[0403] In one implementation, R 10d and R 11d Independently selected from H or C 1-3 Alkyl; or R 10d and R 11dTogether with the carbon atoms to which they are attached, they form cyclopropyl groups.

[0404] In one implementation, R 10d and R 11d It is independently selected from H or methyl.

[0405] In one embodiment, the connection portion of formula L14d is selected from the following: ; ; .

[0406] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0407] In one implementation, L is the connecting portion of formula L14e: (L14e); Where n50 and n51 are independent integer values ​​0 or 1; n52 and n53 are independent integer values ​​of 0, 1 or 2; Cycle G5, cycle H5, and cycle D5 are independently selected from the group consisting of: 4- to 10-membered heterocyclic alkyl groups, 5- or 6-membered heteroaryl groups, and C3-C... 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 8e replace; R 8e Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; and R 10e and R 11e Independently selected from H and C 1-4 Alkyl, C 3-6 cycloalkyl; or R 10e and R 11e Together with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups; R 12e and R 13e Independently selected from H, halogen, C1-4 Alkyl, C 3-6 cycloalkyl; or R 12e and R 13e Together with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups.

[0408] In one implementation, ring H5 can optionally be composed of one or more R... 8e Replacement of 5- or 6-membered heteroaryl groups.

[0409] In one implementation, ring H5 can optionally be composed of one or more R... 8e Substituted pyridinyl ring, pyrimidinyl ring, pyridazinyl ring or pyrazinyl ring.

[0410] In one implementation, ring D5 can optionally be divided by one or more R... 8e The 5- or 6-membered heteroaryl group is replaced. In another embodiment, ring D5 may optionally be replaced by one or more R groups. 8e Substituted 5-membered heteroaryl group.

[0411] In one implementation, ring D5 can optionally be divided by one or more R... 8e Substituted oxazole ring, isoxazole ring, pyrazole ring, imidazole ring, triazole ring, thiazole ring or isothiazole ring.

[0412] In another implementation, ring D5 can optionally be composed of one or more R... 8e The substituted oxazole ring, isoxazole ring, or pyrazole ring. In another embodiment, ring D5 may optionally be replaced by one or more R... 8e Substituted isoxazole ring.

[0413] In one embodiment, cycloG5 is selected from the group consisting of: 4- to 10-membered heterocyclic alkyl groups and C3-C4 groups. 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 8e Replacement. In another embodiment, ring G5 is optionally replaced by one or more R... 8e The substituted 4- to 9-membered heterocyclic alkyl group. In another embodiment, ring G5 is optionally replaced by one or more R groups. 8e The substituted alkyl group is a 4- to 9-membered heterocyclic alkyl group containing one or two nitrogen atoms. In another embodiment, ring G5 is optionally replaced by one or more R atoms. 8e Substituted 4- to 8-membered heterocyclic alkyl groups containing one or two nitrogen atoms.

[0414] In one implementation, R 12e and R 13e Independently selected from H and C 1-4Alkyl group. In another embodiment, R 12e and R 13e It is independently selected from H and methyl.

[0415] In one implementation, R 12e and R 13e One of them is H and the other is methyl. In another embodiment, R 12e and R 13e Both are H.

[0416] In one embodiment, n50 is 1. In another embodiment, n51 is 1. In yet another embodiment, both n50 and n51 are 1. In still another embodiment, n51 is 0.

[0417] In one embodiment, n52 is 1. In another embodiment, n53 is 1. In yet another embodiment, both n52 and n53 are 1. In yet another embodiment, n51 is 0.

[0418] In one embodiment, n53 is 0 and n51 is 1. In another embodiment, n50 is 1 and n52 is 1. In yet another embodiment, n50, n51, n52, and n53 are each 1.

[0419] In one implementation, R 8e Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0420] In another implementation, R 8e Each time it appears, it is independently selected from hydroxyl, =O, and C. 1-4 A group composed of alkyl groups.

[0421] In one implementation, R 10e and R 11e Independently selected from H or C 1-3 Alkyl; or R 10e and R 11e Together with the carbon atoms to which they are attached, they form cyclopropyl groups.

[0422] In one implementation, R 10e and R11e It is independently selected from H or methyl.

[0423] In one embodiment, the connection portion of formula L14e is selected from the following: ; ; ; .

[0424] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0425] In one implementation, L is the connecting portion of formula L15: (L15), Wherein ring D1 is a 5- or 6-membered heteroaryl ring or a phenyl ring, each of which may optionally be surrounded by one or more R groups. 20 replace; n30 is an integer value from 0 to 5; n31 is a value from 1 to 12; and n32 is an integer value of 0 or 1; and R 20 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0426] In one implementation, ring D1 is optionally bounded by one or more R... 20 A substituted 5- or 6-membered heteroaryl ring. Suitablely, D1 is a pyridyl ring, a pyrazolyl ring, or an isoxazolyl ring.

[0427] In one embodiment, n31 is a value from 1 to 8, preferably from 1 to 6. In another embodiment, n31 is a value from 3 to 12, preferably from 3 to 8, preferably about 5.

[0428] In one embodiment, n31 is a value from 3 to 8 and n32 is 1. In another embodiment, n31 is a value of 4, 5, or 6, n32 is 1, and n30 is 1.

[0429] In one implementation, n30 is 0 or 1.

[0430] In one implementation, R 20 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0431] In another implementation, R 20 Each time it appears, it is independently selected from hydroxyl, =O, and C. 1-4 A group composed of alkyl groups.

[0432] In one embodiment, the connection portion of formula L15 is selected from the following: ; ; ; ; .

[0433] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0434] In one implementation, L is the connecting portion of formula L16: (L16); Where ring J can be arbitrarily divided by one or more R. 23 Substituted 5- to 10-membered heterocyclic alkyl rings; n33 is an integer value from 0 to 5; n34 is a value from 1 to 12; and n35 is an integer value of 0 or 1; and R 23 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0435] In one implementation, ring J is optionally bounded by one or more R 23 The substituted 5- to 9-membered heterocyclic alkyl ring suitably contains one or two nitrogen atoms. In one embodiment, ring J is optionally surrounded by one or more R atoms. 23 The substituted 5- or 6-membered heterocyclic alkyl ring suitably contains one or two nitrogen atoms. Suitably, J is optionally replaced by one or more R atoms. 23 Substituted piperidinyl ring or piperazine ring.

[0436] In one embodiment, n34 is a value from 1 to 8, preferably from 1 to 6. In another embodiment, n34 is a value of 1, 2, or 3, preferably 1 or 2, preferably 1.

[0437] In one implementation, n35 is 0.

[0438] In one implementation, n33 is 0, 1, or 2, preferably 0 or 1, preferably 1.

[0439] In one embodiment, n34 is the value 1 and n33 is 1. In one embodiment, n34 is the value 1 and n35 is 0. In another embodiment, n33 is 1, n34 is 1 and n35 is 0.

[0440] In one implementation, R 23 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0441] In another implementation, R 23 Each time it appears, it is independently selected from hydroxyl, =O, and C. 1-4 A group composed of alkyl groups.

[0442] In one embodiment, the connection portion of formula L16 is selected from the following: ; ; ; ; ; .

[0443] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0444] In one implementation, L is the connecting portion of formula L16a: (L16a); Where ring J1 can be arbitrarily divided by one or more Rs 26 Substituted 4- to 10-membered heterocyclic alkyl rings; Z 1 It does not exist or is selected from NH, N(C) 1-3 Alkyl), O, or S groups; n37 and n38 are independently selected from integer values ​​0 to 5; and n36 and n39 are independently selected from integer values ​​0 or 1; and R 26 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0445] In one implementation, ring J1 is optionally bounded by one or more R... 26 The substituted 4- to 9-membered heterocyclic alkyl rings suitably contain one or two nitrogen atoms. In one embodiment, ring J1 is optionally separated by one or more R atoms. 26 The substituted 5- or 6-membered heterocyclic alkyl ring suitably contains one or two nitrogen atoms. Suitably, J1 is optionally surrounded by one or more R atoms. 26 Substituted piperidinyl ring or piperazine ring.

[0446] In one implementation scheme, Z 1 It does not exist or is selected from NH, N(C) 1-3 An alkyl group or an O group. In another embodiment, Z 1 It does not exist or is selected from O, NH or NMe groups.

[0447] In one embodiment, n39 is 0. In another embodiment, n36 is 0. In yet another embodiment, both n39 and n36 are 0. In yet another embodiment, n36 is 1 and n39 is 0.

[0448] In one embodiment, n37 and n38 are independently selected from 0, 1, 2, or 3. In another embodiment, both n37 and n38 are 1.

[0449] In one implementation, n36 is 1 and n37 is 1. In another implementation, n36 is 1, n37 is 1, and n38 is an integer selected from 0, 1, 2, or 3.

[0450] In one implementation, R 26 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0451] In another implementation, R 26 Each time it appears, it is independently selected from hydroxyl, =O, and C. 1-4 A group composed of alkyl groups.

[0452] In one embodiment, the connection portion of formula L16a is selected from the following: ; ; ; ; ; ; ; ; ; ; ; ; ; ; .

[0453] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0454] In one implementation, L is the connecting portion of formula L16b: (L16b); Where ring J2 can be arbitrarily divided by one or more Rs 26b Substituted 4- to 10-membered heterocyclic alkyl rings; Z 2 It does not exist or is selected from NH, N(C) 1-3 Alkyl), O, or S groups; n57 and n58 are independently selected from integer values ​​0 to 5; and n56 and n59 are independently selected from integer values ​​0 or 1; and R 26b Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0455] In one implementation, ring J2 is optionally bounded by one or more R... 26b The substituted 4- to 9-membered heterocyclic alkyl rings suitably contain one or two nitrogen atoms. In one embodiment, ring J2 is optionally separated by one or more R atoms. 26b The substituted 5- or 6-membered heterocyclic alkyl ring suitably contains one or two nitrogen atoms. Suitably, J2 is optionally surrounded by one or more R atoms. 26b Substituted piperidinyl ring or piperazine ring.

[0456] In one implementation scheme, Z 2 It does not exist or is selected from NH, N(C) 1-3 An alkyl group or an O group. In another embodiment, Z 2 It does not exist or is selected from O, NH or NMe groups.

[0457] In one embodiment, n59 is 0. In another embodiment, n56 is 0. In yet another embodiment, both n59 and n56 are 0. In yet another embodiment, n56 is 1 and n59 is 0.

[0458] In one embodiment, n57 and n58 are independently selected from 0, 1, 2, or 3. In another embodiment, both n57 and n58 are 1.

[0459] In one implementation, n56 is 1 and n57 is 1. In another implementation, n56 is 1, n57 is 1, and n58 is an integer selected from 0, 1, 2, or 3.

[0460] In one implementation, R 26b Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0461] In another implementation, R 26b Each time it appears, it is independently selected from hydroxyl, =O, and C. 1-4 A group composed of alkyl groups.

[0462] In one embodiment, the wavy line indicates the attachment point to the protein-binding portion Q. In another embodiment, the wavy line indicates the attachment point to the E3 ubiquitin ligase-binding portion M.

[0463] In one embodiment, the compound of formula I is a compound of sub-formula IA: (IA) Where R 1 R 2a X 1 X 3 X 4 X 6 X 7 X 9 X 10 and n4 are as in any of the implementation schemes mentioned above (in particular, formula Q). 1a-c As defined in the implementation of formula L3; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0464] In one implementation, R 2a It is H.

[0465] In one embodiment, the compound of formula I is a compound of sub-formula IAi: Where R 1 R 2a X 1 X 3 X 4 X 6 X 7 X 9 X 10 and n4a are implementations as mentioned above (in particular, formula Q). 1a-c As defined in the implementation of formula L4; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0466] In one implementation, R 2a It is H.

[0467] In another embodiment, the compound of formula I is a compound of sub-formula IB: (IB) Where R 1 R 2a X 1 X 3 X 4 X 6 X 7 X 9 X 10 n3 and n5 are implementation schemes as mentioned above (in particular, formula Q). 1a-c As defined in the implementation scheme of formula L5; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0468] In one implementation, R 2a It is H.

[0469] In another embodiment, the compound of formula I is a compound of sub-formula IC: (IC) Where R 1 R 2a X 1 X 3 X4 X 6 X 7 X 9 X 10 D, n6, and n7 are implementation schemes as mentioned above (in particular, formula Q). 1a-c As defined in the implementation of formula L8; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0470] In one implementation, R 2a It is H.

[0471] In one embodiment, the compound of formula I is a compound of sub-formula ID: (ID) Where R 1 X 1 X 3 X 4 X 6 X 7 X 15 and n4 are as in any of the implementation schemes mentioned above (in particular, formula Q). 2a-d As defined in the implementation of formula L3; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0472] In another embodiment, the compound of formula I is a compound of sub-formula IDi: (IDi) Where R 1 X 1 X 3 X 4 X 6 X 7 X 15 and n4a are implementations as mentioned above (in particular, formula Q). 2a-d As defined in the implementation of formula L4; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0473] In another embodiment, the compound of formula I is a compound of sub-formula IE: (IE) Where R 1 X 1 X 3X 4 X 6 X 7 X 15 n3 and n5 are implementation schemes as mentioned above (in particular, formula Q). 2a-d As defined in the implementation scheme of formula L5; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0474] In another embodiment, the compound of formula I is a compound of formula IF: (IF) Where R 1 X 1 X 3 X 4 X 6 X 7 X 15 D, n6, and n7 are implementation schemes as mentioned above (in particular, formula Q). 2a-d As defined in the implementation of formula L8; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0475] In one embodiment, the compound of formula I is a compound of formula ITi: Where R 1 R 2a X 1 X 3 X 4 X 6 X 7 X 9 X 10 and n20, n21, n27, G2, H2, R 10 and R 11 This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 1a-c As defined in the implementation of formula L14b; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0476] In one embodiment, the compound of formula I is a compound of sub-formula IGii: Where R 1 R 2a X1 X 3 X 4 X 6 X 7 X 9 X 10 and n20, n21, n27, G2, R 10 and R 11 This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 1a-c As defined in the implementation of formula L14b1; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0477] In one embodiment, the compound of formula I is a compound of sub-formula IGiii: Where R 1 R 2a X 1 X 3 X 4 X 6 X 7 X 9 X 10 and n20, n21, n27, R 10 and R 11 This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 1a-c As defined in the implementation of formula L14b2; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0478] In one embodiment, the compound of formula I is a compound of sub-formula IHi: (IHi) Where R 1 R 2a X 1 X 3 X 4 X 6 X 7 X 9 X 10 and n23, n24, R 12c R 13c G3 and H3 are implementation schemes as mentioned above (in particular, formula Q). 1a-c As defined in the implementation of formula L14c; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0479] In one embodiment, the compound of formula I is a compound of sub-formula IHii: Where R 1 R 2a X 1 X 3 X 4 X 6 X 7 X 9 X 10 and n26, n28, R 12d R 13d Z, G4, H4, R 10d and R 11d This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 1a-c As defined in the implementation of formula L14d; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0480] In one embodiment, the compound of formula I is a compound of sub-formula IHiii: Where R 1 R 2a X 1 X 3 X 4 X 6 X 7 X 9 X 10 and n50, n51, n52, n53, R 12e R 13e D5, G5, H5, R 10e and R 11e This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 1a-c As defined in the implementation of formula L14e; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0481] In one embodiment, the compound of formula I is a compound of sub-formula IJ: (IJ) Where R 1 R2a X 1 X 3 X 4 X 6 X 7 X 9 X 10 and n36, n37, n38, n39, J1 and Z 1 This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 1a-c As defined in the implementation of formula L16a; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0482] In one embodiment of a compound of formula IA, IAi, IB, IC, IGe, IGii, IGiii, IHi, IHii, IHiii, or IJ, X 6 It is N and X 7 It is CH. In another implementation, X 6 It is N, X 7 It is CH and X 9 It is N. In another implementation, X 6 It is N, X 7 It is CH, X 9 It is N and X 10 Is it CH or CR? 3 , where R 3 It is as defined in any of the implementation schemes mentioned above.

[0483] In one embodiment of a compound of formula IA, IAi, IB, IC, IGe, IGii, IGiii, IHi, IHii, IHiii, or IJ, X 6 It is N, X 3 It is N and X 7 It is CH. In another implementation, X 6 It is N, X 3 It is N, X 7 It is CH and X 9 It is N. In another implementation, X 6 It is N, X 3 It is N, X 7 It is CH, X 9 It is N and X 10 Is it CH or CR? 3 , where R 3 It is as defined in any of the implementation schemes mentioned above.

[0484] In one embodiment of a compound of formula IA, IAi, IB, IC, IGe, IGii, IGiii, IHi, IHii, IHiii, or IJ, X 6 It is N, X 3 It is N, X 4 It is CH and X 7 It is CH. In another implementation, X 6 It is N, X 3 It is N, X 4 It is CH, X 7 It is CH and X 9 It is N. In another implementation, X 6 It is N, X 3 It is N, X 4 It is CH, X 7 It is CH, X 9 It is N and X 10 Is it CH or CR? 3 , where R 3 It is as defined in any of the implementation schemes mentioned above.

[0485] In one embodiment of a compound of formula IA, IAi, IB, IC, IGe, IGii, IGiii, IHi, IHii, IHiii, or IJ, X 6 It is N, X 1 It is CH, X 3 It is N, X 4 It is CH and X 7 It is CH. In another implementation, X 6 It is N, X 1 It is CH, X 3 It is N, X 4 It is CH, X 7 It is CH and X 9 It is N. In another implementation, X 6 It is N, X 1 It is CH, X 3 It is N, X 4 It is CH, X 7 It is CH, X 9 It is N and X 10 Is it CH or CR? 3 , where R 3 It is as defined in any of the implementation schemes mentioned above.

[0486] In another implementation, X 6 It is C and X 7 It is S. In another implementation, X 6 It is C, X7 It is S and X 9 It is N. In another implementation, X 6 It is C, X 7 It is S, X 9 It is N and X 10 Is it CH or CR? 3 , where R 3 It is as defined in any of the implementation schemes mentioned above.

[0487] In another implementation, X 6 It is C, X 1 X 3 and X 4 It is CH and X 7 It is S. In another implementation, X 6 It is C, X 1 X 3 and X 4 It is CH, X 7 It is S and X 9 It is N. In another implementation, X 6 It is C, X 1 X 3 and X 4 It is CH, X 7 It is S, X 9 It is N and X 10 Is it CH or CR? 3 , where R 3 It is as defined in any of the implementation schemes mentioned above.

[0488] In one implementation, R 2a It is hydrogen. In one implementation, X 10 Is it CH or CR? 3 In one implementation, R 2a It is methyl, and X 10 It is CH. In another implementation, R 2a It is H and X 10 It is CR 3 Appropriately R 3 It is methyl or ethyl.

[0489] In one embodiment, the compound of formula I is a compound of sub-formula IKi: Where R 1 X 1 X 3 X 4 X 6 X 7 X 15and n20, n21, G2, H2, R 10 and R 11 This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 2a-d As defined in the implementation of formula L14b; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0490] In one embodiment, the compound of formula I is a compound of sub-formula IKii: (IKii) Where R 1 X 1 X 3 X 4 X 6 X 7 X 15 and n20, n21, n27, G2, R 10 and R 11 This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 2a-d As defined in the implementation of formula L14b1; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0491] In one embodiment, the compound of formula I is a compound of sub-formula IKiii: Where R 1 X 1 X 3 X 4 X 6 X 7 X 15 and n20, n21, n27, R 10 and R 11 This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 2a-d As defined in the implementation of formula L14b2; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0492] In one embodiment, the compound of formula I is a compound of sub-formula ILi: (ILi) Where R 1 X 1 X3 X 4 X 6 X 7 X 15 and n23, n24, R 12c R 13c G3 and H3 are implementation schemes as mentioned above (in particular, formula Q). 2a-d As defined in the implementation of formula L14c; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0493] In one embodiment, the compound of formula I is a compound of sub-formula ILii: Where R 1 X 1 X 3 X 4 X 6 X 7 X 15 and n26, n28, R 12d R 13d Z, G4, H4, R 10d and R 11d This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 2a-d As defined in the implementation of formula L14d; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0494] In one embodiment, the compound of formula I is a compound of sub-formula ILiii: Where R 1 X 1 X 3 X 4 X 6 X 7 X 15 and n50, n51, n52, n53, R 12e R 13e D5, G5, H5, R 10e and R 11e This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 2a-d As defined in the implementation of formula L14e; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0495] In one embodiment, the compound of formula I is a compound of sub-formula IM: (IM) Where R 1 X 1 X 3 X 4 X 6 X 7 X 15 and n36, n37, n38, n39, J1 and Z 1 This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 2a-d As defined in the implementation of formula L16a; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0496] In one embodiment of a compound of formulas ID, IDi, IE, IF, IKi, IKii, IKiii, Ili, ILii, ILiii, and IM, X 6 It is N and X 7 It is CH. In another implementation, X 6 It is N, X 7 It is CH and X 15 It is O, NMe, or CH.

[0497] In one embodiment of a compound of formulas ID, IDi, IE, IF, IKi, IKii, IKiii, Ili, ILii, ILiii, and IM, X 6 It is N, X 3 It is N and X 7 It is CH. In another implementation, X 6 It is N, X 3 It is N, X 7 It is CH and X 15 It is O, NMe, or CH.

[0498] In one embodiment of a compound of formulas ID, IDi, IE, IF, IKi, IKii, IKiii, Ili, ILii, ILiii, and IM, X 6 It is N, X 3 It is N, X 4 It is CH and X 7It is CH. In another implementation, X 6 It is N, X 3 It is N, X 4 It is CH, X 7 It is CH and X 15 It is O, NMe, or CH.

[0499] In one embodiment of a compound of formulas ID, IDi, IE, IF, IKi, IKii, IKiii, Ili, ILii, ILiii, and IM, X 6 It is N, X 1 It is CH, X 3 It is N, X 4 It is CH and X 7 It is CH. In another implementation, X 6 It is N, X 1 It is CH, X 3 It is N, X 4 It is CH, X 7 It is CH and X 15 It is O, NMe, or CH.

[0500] In another implementation, X 6 It is C and X 7 It is S. In another implementation, X 6 It is C, X 7 It is S and X 15 It is O, NMe, or CH.

[0501] In another implementation, X 6 It is C, X 1 X 3 and X 4 It is CH and X 7 It is S. In another implementation, X 6 It is C, X 1 X 3 and X 4 It is CH, X 7 It is S and X 15 It is O, NMe, or CH.

[0502] In one implementation, R 2a It is hydrogen. In one implementation, X 10 Is it CH or CR? 3 In one implementation, R 2a It is methyl, and X 10 It is CH. In another implementation, R 2a It is H and X 10 It is CR 3 Appropriately R3 It is a methyl group.

[0503] In one embodiment, the compound of formula I is a compound of sub-formula INi: (INi) Where R 1 R 2a X 1 X 7a X 9 X 10 and n4 are as in any of the implementation schemes mentioned above (in particular, formula Q). 1d As defined in the implementation of formula L3; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0504] In one embodiment, the compound of formula I is a compound of sub-formula INii: (INii) Where R 1 R 2a X 1 X 7a X 9 X 10 and n4a are implementations as mentioned above (in particular, formula Q). 1d As defined in the implementation of formula L4; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0505] In one embodiment, the compound of formula I is a compound of sub-formula INiii: Where R 1 R 2a X 1 X 7a X 9 X 10 and n20, n21, n27, G2, H2, R 10 and R 11 This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 1d As defined in the implementation of formula L14b; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0506] In one embodiment, the compound of formula I is a compound of sub-formula INiv: Where R 1 R 2a X 1 X 7a X 9 X 10 and n20, n21, n27, G2, R 10 and R 11 This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 1d As defined in the implementation of formula L14b1; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0507] In one embodiment, the compound of formula I is a compound of sub-formula INv: Where R 1 R 2a X 1 X 7a X 9 X 10 and n20, n21, n27, R 10 and R 11 This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 1d As defined in the implementation of formula L14b2; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0508] In one embodiment, the compound of formula I is a compound of sub-formula INvi: (INvi) Where R 1 R 2a X 1 X 7a X 9 X 10 and n23, n24, R 12c R 13c G3 and H3 are implementation schemes as mentioned above (in particular, formula Q). 1d As defined in the implementation of formula L14c; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0509] In one embodiment, the compound of formula I is a compound of sub-formula INvii: Where R 1 R 2a X 1 X 7a X 9 X 10 and n26, n28, R 12d R 13d Z, G4, H4, R 10d and R 11d This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 1d As defined in the implementation of formula L14d; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0510] In one embodiment, the compound of formula I is a compound of sub-formula INviii: (INviii) Where R 1 R 2a X 1 X 7a X 9 X 10 and n36, n37, n38, n39, J1 and Z 1 This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 1d As defined in the implementation of formula L16a; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0511] In one embodiment of a compound of formula INi, INii, INiii, INiv, INv, INvi, INvii, or INviii, X 1 It is N and X 7a It is CH. In another implementation, X 1 It is N, X 7a It is CH and X 9 It is N. In another implementation, X 1 It is N, X 7a It is CH, X 9 It is N and X 10 Is it CH or CR? 3 , where R3 It is as defined in any of the implementation schemes mentioned above.

[0512] In another embodiment of a compound of formula INi, INii, INiii, INiv, INv, INvi, INvii, or INviii, X 1 It is CH and X 7a It is N. In another implementation, X 1 It is CH, X 7a It is N and X 9 It is N. In another implementation, X 1 It is CN, X 7a It is N, X 9 It is N and X 10 Is it CH or CR? 3 , where R 3 It is as defined in any of the implementation schemes mentioned above.

[0513] In another embodiment of a compound of formula INi, INii, INiii, INiv, INv, INvi, INvii, or INviii, X 1 It is CH and X 7a It is CH. In another implementation, X 1 It is CH, X 7a It is CH and X 9 It is N. In another implementation, X 1 It is CH, X 7a It is CH, X 9 It is N and X 10 Is it CH or CR? 3 , where R 3 It is as defined in any of the implementation schemes mentioned above.

[0514] In one embodiment, the compound of formula I is a compound of the sub-formula IPi: (IPi) Where R 1 X 1 X 7b X 15 and n4 are as in any of the implementation schemes mentioned above (in particular, formula Q). 2e As defined in the implementation of formula L3; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0515] In another embodiment, the compound of formula I is a compound of sub-formula IPii: (IPii) Where R 1 X 1 X 7b X 15 and n4a are implementations as mentioned above (in particular, formula Q). 2e As defined in the implementation of formula L4; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0516] In one embodiment, the compound of formula I is a compound of sub-formula IPiii: Where R 1 X 1 X 7b X 15 and n20, n21, G2, H2, R 10 and R 11 This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 2e As defined in the implementation of formula L14b; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0517] In one embodiment, the compound of formula I is a compound of sub-formula IPiv: (IPiv) Where R 1 X 1 X 7b X 15 and n20, n21, n27, G2, R 10 and R 11 This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 2e As defined in the implementation of formula L14b1; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0518] In one embodiment, the compound of formula I is a compound of sub-formula IPv: (IPv) Where R 1 X 1 X 7b X 15and n20, n21, n27, R 10 and R 11 This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 2e As defined in the implementation of formula L14b2; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0519] In one embodiment, the compound of formula I is a compound of sub-formula IPvi: (IPvi) Where R 1 X 1 X 7b X 15 and n23, n24, R 12c R 13c G3 and H3 are implementation schemes as mentioned above (in particular, formula Q). 2e As defined in the implementation of formula L14c; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0520] In one embodiment, the compound of formula I is a compound of sub-formula IPvii: (IPvii) Where R 1 X 1 X 7b X 15 and n26, n28, R 12d R 13d Z, G4, H4, R 10d and R 11d This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 2e As defined in the implementation of formula L14d; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0521] In one embodiment, the compound of formula I is a compound of sub-formula IPviii: (IPviii) Where R 1 X 1 X 7b X 15 and n36, n37, n38, n39, J1 and Z1 This is as described in any of the implementation schemes mentioned above (in particular, scheme Q). 2e As defined in the implementation of formula L16a; and M is the E3 ubiquitin ligase-binding moiety, suitably selected from the E3 ubiquitin ligase-binding moiety of any of the embodiments mentioned below.

[0522] In one embodiment of a compound of formula IPi, IPii, IPiii, IPiv, IPv, IPvi, IPvii, or IPviii, X 1 It is N and X 7b It is CH. In another implementation, X 1 It is N, X 7b It is CH and X 15 It is O, NMe, or CH.

[0523] In one embodiment of a compound of formula IPi, IPii, IPiii, IPiv, IPv, IPvi, IPvii, or IPviii, X 1 It is CH and X 7b It is N. In another implementation, X 1 It is CH, X 7b It is N and X 15 It is O, NMe, or CH.

[0524] In one embodiment of a compound of formula IPi, IPii, IPiii, IPiv, IPv, IPvi, IPvii, or IPviii, X 1 It is CH and X 7b It is CH. In another implementation, X 1 It is CH, X 7b It is CH and X 15 It is O, NMe, or CH.

[0525] E3 ubiquitin ligase binding site M The E3 ubiquitin ligase-binding moiety M is capable of binding to an E3 ubiquitin ligase. In one embodiment, M is an E3 ubiquitin ligase-binding moiety capable of binding to von Hippel-Lindau (VHL) E3 ligase, cereblon (CRBN) E3 ligase, or inhibitor of apoptosis protein (IAP) E3 ligase (e.g., c-IAP1, c-IAP2, XIAP).

[0526] In one embodiment, M is an E3 ubiquitin ligase binding moiety capable of binding to either the Hipper-Lindau (VHL) E3 ligase or the cereblon (CRBN) E3 ligase.

[0527] In another embodiment, M is an E3 ubiquitin ligase binding moiety capable of binding to Hippel-Lindau (VHL) E3 ligases or Inhibitor of Apoptosis (IAP) E3 ligases (e.g., c-IAP1, c-IAP2, XIAP).

[0528] In another embodiment, M is the E3 ubiquitin ligase-binding moiety of formula M1: (M1); in R M1a It can be optionally converted by halogens, -OH, -O(C) 1-4 alkyl), -S(C 1-4 alkyl) substituted C 2-6 alkyl groups; R M1b Selected from hydrogen or optionally converted by -C(O)N(H)Me, -OH, -NH2, -NH(C 1-4 alkyl), -N(C) 1-4 C-substituted with alkyl groups, -CO2Et, and -COOH 1-6 Alkyl; and R M1c Choose from the following groups: halogens, -NO2, -CN, C 2-4 Alkyne, 5-6 heteroaryl, and phenyl, wherein the 5-6 heteroaryl and phenyl groups are optionally selected from one or more halogens and C. 1-3 Alkyl groups are substituted; and The wavy line represents the attachment point with L.

[0529] In one implementation, R M1a It is C 3-6 Alkyl groups.

[0530] In one implementation, R M1a It is an isopropyl group or a tert-butyl group.

[0531] In one implementation, R M1b Selected from hydrogen or C that can be optionally substituted with -C(O)N(H)Me, CO2Et and COOH 1-6 Alkyl group. In one embodiment, R M1b Selected from hydrogen or methyl.

[0532] In another implementation, when R M1bWhen it is not hydrogen, the substituents result in the following stereochemistry at the chiral carbon: S Configuration. In one implementation, R M1b yes( S )-methyl.

[0533] In one implementation, R M1a It is a tert-butyl group, and R M1b Selected from hydrogen or methyl, suitably ( S )-methyl.

[0534] In one implementation, R M1c It is a 5-6-membered heteroaryl and phenyl group, wherein the 5-6-membered heteroaryl and phenyl group is optionally selected from one or more halogens and C. 1-3 Alkyl groups are substituted.

[0535] In another implementation, R M1c It is CN or optionally selected from one or more halogens and C. 1-3 The alkyl group is substituted with a 5-6 membered heteroaryl group. In another embodiment, R M1c It is optionally selected by one or more halogens and C 1-3 A 5-membered heteroaryl group substituted with an alkyl group. Suitablely, R M1c It is optionally selected by one or more halogens and C 1-3 Thiazoles or oxazoles with alkyl groups substituted.

[0536] In another implementation, R M1c Selected from: .

[0537] In one embodiment, the E3 ubiquitin ligase-binding moiety of formula M1 is: , Where R M1b Is it H or ( S )-methyl, and the wavy line indicates the attachment point with L.

[0538] In another embodiment, M is the E3 ubiquitin ligase-binding moiety of formula M2: (M2); in R M2a It can be optionally converted by halogens, -OH, -O(C) 1-4 alkyl), -S(C 1-4 alkyl) substituted C 2-6 alkyl groups; R M2d Selected from: ; R M2b Selected from hydrogen or optionally converted by -C(O)N(H)Me, -OH, -NH2, -NH(C 1-4 alkyl), -N(C) 1-4 C-substituted with alkyl groups, -CO2Et, and -COOH 1-6 Alkyl; and R M2c Choose from the following groups: halogens, -NO2, -CN, C 2-4 Alkyne, 5-6 heteroaryl, and phenyl, wherein the 5-6 heteroaryl and phenyl groups are optionally selected from one or more halogens and C. 1-3 Alkyl groups are substituted; and The wavy line represents the attachment point with L.

[0539] In one implementation, R M2a It is C 3-6 Alkyl groups, preferably isopropyl or tert-butyl groups.

[0540] In one implementation, R M2b Selected from hydrogen or C, which may optionally be replaced by -C(O)N(H)Me, CO2Et and -COOH 1-6 Alkyl group. In another embodiment, R M2b Selected from hydrogen or methyl.

[0541] In another implementation, when R M2b When it is not hydrogen, the substituents result in the following stereochemistry at the chiral carbon: S Configuration. In one implementation, R M2b yes( S )-methyl.

[0542] In one implementation, R M2a It is a tert-butyl group, and R M2b Selected from hydrogen or methyl, suitably ( S )-methyl.

[0543] In one implementation, R M2c It is -CN or optionally selected by one or more halogens and C 1-3 The alkyl group is substituted with a 5-6 membered heteroaryl group. In another embodiment, R M2c It is optionally selected by one or more halogens and C 1-3 A 5-membered heteroaryl group substituted with an alkyl group. Suitablely, R M2c It is optionally selected by one or more halogens and C 1-3 Thiazoles or oxazoles with alkyl groups substituted.

[0544] In another implementation, R M2c Selected from: .

[0545] In one implementation, R M2d Selected from: .

[0546] In one embodiment, the E3 ubiquitin ligase-binding moiety of formula M2 is: , where R M2e Is it F or CN, R? M2b Is it hydrogen or methyl (appropriately) S -methyl), and the wavy line indicates the attachment point with L.

[0547] In another embodiment, the E3 ubiquitin ligase-binding moiety of formula M2 is: or , The wavy line represents the attachment point with L.

[0548] In another embodiment, the E3 ubiquitin ligase-binding moiety of formula M2 is: or , The wavy line represents the attachment point with L.

[0549] In another embodiment, M is the E3 ubiquitin ligase-binding moiety of formula M3: (M3); in R M3a It can be optionally converted by halogens, -OH, -O(C) 1-4 alkyl), -S(C 1-4 alkyl) substituted C 2-6 alkyl groups; R M3d Selected from: ; R M3c Choose from the following groups: halogens, -NO2, -CN, C 2-4 Alkyne, 5-6 heteroaryl, and phenyl, wherein the 5-6 heteroaryl and phenyl groups are optionally selected from one or more halogens and C. 1-3 Alkyl groups are substituted; and The wavy line represents the attachment point with L.

[0550] In one implementation, RM3a It is C 3-6 Alkyl groups, suitably R M3a It is an isopropyl group or a tert-butyl group.

[0551] In one implementation, R M3d Selected from: .

[0552] In one implementation, R M3c It is a 5-6-membered heteroaryl and phenyl group, wherein the 5-6-membered heteroaryl and phenyl group is optionally selected from one or more halogens and C. 1-3 Alkyl groups are substituted.

[0553] In one implementation, R M3c It is CN or optionally selected from one or more halogens and C. 1-3 The alkyl group is substituted with a 5-6 membered heteroaryl group. In another embodiment, R M3c It is optionally selected by one or more halogens and C 1-3 A 5-membered heteroaryl group substituted with an alkyl group. Suitablely, R M1c It is optionally selected by one or more halogens and C 1-3 Thiazoles or oxazoles with alkyl groups substituted.

[0554] In another implementation, R M3c Selected from: .

[0555] In one embodiment, the E3 ubiquitin ligase-binding moiety of formula M3 is: ; The wavy line represents the attachment point with L.

[0556] In another embodiment, M is the E3 ubiquitin ligase-binding moiety of formula M4: (M4) Where R M4 Selected from -NH-, O, OCH2C(O)NH-, -C≡C-, CH2 and -NH(CO)-.

[0557] In one embodiment, the E3 ubiquitin ligase-binding portion of formula M4 is selected from: .

[0558] In another embodiment, M is the E3 ubiquitin ligase-binding moiety of formula M5: Where RM5 Selected from -NH- or -O-.

[0559] In one embodiment, the E3 ubiquitin ligase-binding moiety of formula M5 is: .

[0560] In another embodiment, M is the E3 ubiquitin ligase-binding moiety of formula M6: (M6); in R M6a It can be optionally converted by halogens, -OH, -O(C) 1-4 alkyl), -S(C 1-4 alkyl) substituted C 2-6 alkyl groups; R M6b Selected from hydrogen or optionally converted by -C(O)N(H)Me, -OH, -NH2, -NH(C 1-4 alkyl), -N(C) 1-4 C-substituted with alkyl groups, -CO2Et, and -COOH 1-6 Alkyl; and R M6c Choose from the following groups: halogens, -NO2, -CN, C 2-4 Alkyne, 5-6 heteroaryl, and phenyl, wherein the 5-6 heteroaryl and phenyl groups are optionally selected from one or more halogens and C. 1-3 Alkyl group substitution; R M6d It is optionally selected by one or more halogens, -O(C 1-3 alkyl) and C 1-3 Alkyl groups substituted with 5- or 6-membered heteroaryl groups; and The wavy line represents the attachment point with L.

[0561] In one implementation, R M6a It is an isopropyl group or a tert-butyl group, each optionally coated with a halogen, -OH, or -O(C) group. 1-4 alkyl), -S(C 1-4 Alkyl) substitution.

[0562] In one implementation, R M6b Selected from hydrogen or methyl.

[0563] In another implementation, when R M6b When it is not hydrogen, the substituents result in the following stereochemistry at the chiral carbon: S Configuration. In one implementation, R M6b yes( S)-methyl.

[0564] In one implementation, R M6a It is a tert-butyl group or an isopropyl group, and R M6b Selected from hydrogen or methyl, suitably ( S )-methyl.

[0565] In one implementation, R M6c It is a 5-6-membered heteroaryl and phenyl group, wherein the 5-6-membered heteroaryl and phenyl group is optionally selected from one or more halogens and C. 1-3 Alkyl groups are substituted.

[0566] In another implementation, R M6c It is CN or optionally selected from one or more halogens and C. 1-3 The alkyl group is substituted with a 5-6 membered heteroaryl group. In another embodiment, R M6c It is optionally selected by one or more halogens and C 1-3 A 5-membered heteroaryl group substituted with an alkyl group. Suitablely, R M6c It is optionally selected by one or more halogens and C 1-3 Thiazoles or oxazoles with alkyl groups substituted.

[0567] In another implementation, R M6c Selected from: .

[0568] In one implementation, R M6d It is a 5-membered heteroaryl group, suitably selected from triazoles, oxazoles, isoxazoles, pyrazoles, imidazoles, thiazoles, and isothiazoles, each optionally being selected by one or more of halogens, -O(C 1-3 alkyl) and C 1-3 Alkyl groups are substituted. In another embodiment, R M6d It is a triazole (suitably 1,2,3-triazole) group or an isoxazole group, each optionally being surrounded by one or more groups selected from halogen, -O(C 1-3 alkyl) and C 1-3 Alkyl groups are substituted.

[0569] In another implementation, R M6d Selected from: , The wavy line represents the attachment point with L.

[0570] In one embodiment, the E3 ubiquitin ligase-binding moiety of formula M6 is: , Where RM6b Is it H or ( S )-methyl, and the wavy line indicates the attachment point with L.

[0571] In one embodiment, the compound of formula I is a compound of sub-formula ISi: (ISi) Among them, n20, n21, n27, G2, H2, R 10 R 11 R M1a R M1b and R M1c It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L14b and M1); and Q is the formula Q 1 or Q 2 The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q 2b Formula Q 2c Formula Q 2d Formula Q 2e Formula Q 2f Or its implementation plan.

[0572] In one embodiment, the compound of formula I is a compound of sub-formula ISii: (ISii) Among them, n20, n21, n27, G2, R 10 R 11 R M1a R M1b and R M1c It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L14b1 and M1); and Q is the formula Q 1 or Q 2 The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q 2b Formula Q 2c Formula Q 2d Formula Q2e Formula Q 2f Or its implementation plan.

[0573] In one embodiment, the compound of formula I is a compound of sub-formula ISiii: (ISiii) Among them, n20, n21, n27, G2, R 10 R 11 R M1a R M1b and R M1c It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L14b2 and M1); and Q is the formula Q 1 or Q 2 The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q 2b Formula Q 2c Formula Q 2d Formula Q 2e Formula Q 2f Or its implementation plan.

[0574] In one embodiment, the compound of formula I is a compound of sub-formula ISiv: Among them, n50, n51, n52, n53, and R 12e R 13e D5, G5, H5, R 10e and R 11e R M1a R M1b and R M1c It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L14e and M1); and Q is the formula Q 1 or Q 2 The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q 2b Formula Q 2cFormula Q 2d Formula Q 2e Formula Q 2f Or its implementation plan.

[0575] In one embodiment, the compound of formula I is a compound of sub-formula ISV: (ISv) Among them, n36, n37, n38, n39, J1 and Z 1 R M1a R M1b and R M1c It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L16a and M1); and Q is the formula Q 1 or Q 2 The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q 2b Formula Q 2c Formula Q 2d Formula Q 2e Formula Q 2f Or its implementation plan.

[0576] In one embodiment, the compound of formula I is a compound of sub-formula ISvi: (ISvi) Among them, n47, n48, n49, K3, R 12 and R 13 and R M1a R M1b and R M1c It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L11c and M1); and Q is the formula Q 1 or Q 2 The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q 2b Formula Q 2c Formula Q 2d Formula Q 2eFormula Q 2f Or its implementation plan.

[0577] In one embodiment, in any of the preceding formulas of compound I, R M1a It is an isopropyl group or a tert-butyl group, and R M1b Selected from hydrogen or methyl.

[0578] In another implementation, R M1c It is optionally selected by one or more halogens and C 1-3 A 5-membered heteroaryl group substituted with an alkyl group; and R M1a It is an isopropyl group or a tert-butyl group, and R M1b Selected from hydrogen or methyl.

[0579] Appropriately, R M1c It is optionally selected by one or more halogens and C 1-3 Thiazoles or oxazoles with alkyl groups substituted.

[0580] In one embodiment, the compound of formula I is a compound of formula IT: (IT) Among them, n45, n42, K2, n43, n44, R M2a R M2b R M2c and R M2d It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L11b and M2); and Q is the formula Q 1 or Q 2 The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q 2b Formula Q 2c Formula Q 2d Formula Q 2e Formula Q 2f Or its implementation plan.

[0581] In one implementation, n44 and n45 are independently selected from the values ​​1, 2, or 3, preferably 1 or 2, preferably 1.

[0582] In another embodiment, n42 and n43 are independently selected from integer values ​​0 to 5, preferably 0 to 3. In another embodiment, n42 and n43 are independently integer values ​​0, 1, or 2, preferably 0 or 1.

[0583] In one implementation, both n42 and n43 are 0. In another implementation, both n42 and n43 are 0, and both n44 and n45 are 1.

[0584] In one embodiment, the compound of formula I is a compound of sub-formula ITi: (ITi) Among them, n47, n48, n49, K3, R 12 and R 13 R M2a R M2b R M2c and R M2d It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L11c and M2); and Q is the formula Q 1 or Q 2 The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q 2b Formula Q 2c Formula Q 2d Formula Q 2e Formula Q 2f Or its implementation plan.

[0585] In one embodiment, the compound of formula I is a compound of sub-formula ITii: (ITii) Among them, n36, n37, n38, n39, J1 and Z 1 R M2a R M2b R M2c and R M2d It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L16a and M2); and Q is the formula Q 1 or Q 2 The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q2b Formula Q 2c Formula Q 2d Formula Q 2e Formula Q 2f Or its implementation plan.

[0586] In one implementation, in any of the sub-formulas mentioned above in Formula I, R M2a It is an isopropyl group or a tert-butyl group, and R M2b Selected from hydrogen or methyl.

[0587] In another implementation, R M2c It is optionally selected by one or more halogens and C 1-3 A 5-membered heteroaryl group substituted with an alkyl group; and R M2a It is an isopropyl group or a tert-butyl group, and R M1b Selected from hydrogen or methyl.

[0588] Appropriately, R M2c It is optionally selected by one or more halogens and C 1-3 Thiazoles or oxazoles with alkyl groups substituted.

[0589] In one implementation, R M2d Selected from: .

[0590] In one embodiment, the compound of formula I is a compound of sub-formula IU: (IU) Among them, n16, n17, and R M2a R M2b R M2c and R M2d It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L13 and M2); and Q is the formula Q 1 or Q 2 The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q 2b Formula Q 2c Formula Q 2d Formula Q 2e Formula Q 2f Or its implementation plan.

[0591] In one implementation, n16 is 0. In another implementation, n16 is 0, and n17 is a value from 1 to 6, suitably 3, 4, or 5.

[0592] In one implementation, R M2a It is an isopropyl group or a tert-butyl group, and R M2b Selected from hydrogen or methyl.

[0593] In another implementation, R M2c It is optionally selected by one or more halogens and C 1-3 A 5-membered heteroaryl group substituted with an alkyl group; and R M1a It is an isopropyl group or a tert-butyl group, and R M1b Selected from hydrogen or methyl.

[0594] Appropriately, R M2c It is optionally selected by one or more halogens and C 1-3 Thiazoles or oxazoles with alkyl groups substituted.

[0595] In one implementation, R M2d Selected from: .

[0596] In one embodiment, the compound of formula I is a compound of sub-formula IVi: (IVi) Among them, n36, n37, n38, n39, J1 and Z 1 R M3a R M3c and R M3d It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L16a and M3); and Q is the formula Q 1 or Q 2 The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q 2b Formula Q 2c Formula Q 2d Formula Q 2e Formula Q 2f Or its implementation plan.

[0597] In one implementation scheme of the IVi scheme, R M3d Selected from: And R M3c Selected from: .

[0598] In one embodiment, the compound of formula I is a compound of sub-formula IWi: (IWi) Among them, n36, n37, n38, n39, J1 and Z 1 R M6a R M6b R M6c and R M6d It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L16a and M6); and Q is the formula Q 1 or Q 2 The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q 2b Formula Q 2c Formula Q 2d Formula Q 2e Formula Q 2f Or its implementation plan.

[0599] In one embodiment, the compound of formula I is a compound of sub-formula IWib: (IWib) Among them, n56, n57, n58, n59, J2 and Z 2 R M6a R M6b R M6c and R M6d It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L16b and M6); and Q is the formula Q 1 or Q 2 The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q 2b Formula Q 2c Formula Q2d Formula Q 2e Formula Q 2f Or its implementation plan.

[0600] In one implementation, n59 is 0 and R M6d yes Appropriately, Z 2 It is selected from NH, N(C) 1-3 Alkyl groups or O groups; In one embodiment, the compound of formula I is a compound of sub-formula IWii: (IWii) Among them, n20, n21, n27, G2, H2, R 10 R 11 R M6a R M6b R M6c and R M6d It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L14b and M6); and Q is the formula Q 1 or Q 2 The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q 2b Formula Q 2c Formula Q 2d Formula Q 2e Formula Q 2f Or its implementation plan.

[0601] In one embodiment, the compound of formula I is a compound of sub-formula IWiii: (IWiii) Among them, n23, n24, and R 12c R 13c G3 and H3, R M6a R M6b R M6c and R M6d It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L14c and M6); and Q is the formula Q 1 or Q 2The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q 2b Formula Q 2c Formula Q 2d Formula Q 2e Formula Q 2f Or its implementation plan.

[0602] In one embodiment, the compound of formula I is a compound of sub-formula IWiv: (IWiv) Among them, n45, n42, K2, n43, n44, R M6a R M6b R M6c and R M6d It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L11b and M6); and Q is the formula Q 1 or Q 2 The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q 2b Formula Q 2c Formula Q 2d Formula Q 2e Formula Q 2f Or its implementation plan.

[0603] In one embodiment, the compound of formula I is a compound of sub-formula IWv: (IWv) Among them, n47, n48, n49, K3, R 12 and R 13 R M6a R M6b R M6c and R M6d It is as defined in any of the implementation schemes mentioned above (in particular, the implementation schemes of L11c and M6); and Q is the formula Q 1 or Q 2The protein-binding portion of Q is suitably selected from the protein-binding portions of any of the embodiments mentioned above. For example, Q can be selected from the group consisting of: formula Q 1a Formula Q 1b Formula Q 1c Formula Q 1d Formula Q 2a Formula Q 2b Formula Q 2c Formula Q 2d Formula Q 2e Formula Q 2f Or its implementation plan.

[0604] In one implementation of a sub-formula of equation I above, R M6a It is an isopropyl group or a tert-butyl group. In another embodiment, R M6b Selected from hydrogen or methyl.

[0605] In one implementation of a sub-formula of equation I above, R M6c Selected from: .

[0606] In another implementation of the sub-formula of Equation I above, R M6d Selected from: , The wavy line represents the attachment point with L.

[0607] In one embodiment, the compound of formula I is selected from the following or their salts, solvates or prodrugs: .

[0608] In another embodiment, the compound of formula I is selected from the following or their salts, solvates or prodrugs: .

[0609] In another embodiment, the compound of formula I is selected from the following or their salts, solvates or prodrugs: .

[0610] In another embodiment, the compound of formula I is selected from the following or their salts, solvates or prodrugs: .

[0611] The invention will now be further described by way of the following numbered items: 1. A compound of formula I or a salt, solvate, or prodrug thereof: in Q is the formula Q 1 or Q 2 Protein-binding portion: (Q 1 ) (Q 2 ) in R 1 Choose the group consisting of the following items: C 3-11 cycloalkyl, C 3-11 cycloalkyl (C 1-3 )alkyl, 3- to 12-membered heterocyclic alkyl, 3- to 12-membered heterocyclic alkyl (C 1-3 )alkyl, 5- to 12-membered heteroaryl (C 1-6 )alkyl, C 1-10 Alkyl, C 2-10 alkenyl and C 2-10 Alkyne groups, wherein each is optionally surrounded by one or more R groups a1 replace; Each R a1 Choose independently the group consisting of: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -OC 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=O)R b1 -C(=O)NR d1 R e1 -NR d1 R e1 -NR d1 C(=O)R b1 -OR c1 -SR c1 -OC(=O)R b1 -S(=O)2Rc1 and -S(=O)2NR d1 R e1 Wherein C 1-6 Alkyl, OC 1-6 Alkyl, C 3-6 cycloalkyl, -OC 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl and C 6-11 The aryl group is optionally substituted by one or more groups selected from the following: hydroxyl, halogen, =O, -CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl, phenyl, -C(O)C 1-6 Alkyl, -C(O)N(H)C 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl group 2, -CONH2, -C(O)N(H)C 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl)2、-N(H)C 1-6 Alkyl and -N(C) 1-6 Alkyl)2; Where R b1 R c1 R d1 and R e1 Choose independently the group consisting of: hydrogen, hydroxyl, C 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 alkyl and phenyl, wherein the C 1-6 Alkyl, -OC 1-6 Alkyl, phenyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl; or R d1 and R e1When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f1 replace; Each R f1 Choose independently the group consisting of the following items: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, phenyl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl; R 2 It is H, C 1-6 Alkyl, C 3-6 cycloalkyl or C 3-6 cycloalkyl-CH2-; B is selected from 5- to 12-membered heteroaryl groups or C 6-11 Aromatic cyclic groups; C is a heterocycle containing at least one nitrogen atom in the ring, and wherein -COOR 1 Part of it is bonded to the ring C via nitrogen atoms in the ring C; A is a cyclic group selected from 5-membered to 15-membered heteroaryl groups; V is selected from the following groups: -NH-, -C(O)N(H)-, -N(H)C(O)-, -S(O)(NH)-, -N(H)S(O)-, -S(O)N(H)-, -N(H)S(O)2- and -S(O)2N(H)-; R 3 and R 9 Choose independently the group consisting of: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=O)R b3 -C(=O)OR c3 -C(=O)NR d3 R e3 -NR d3 R e3 -NR d3 C(=O)R b3 -ORc3 -SR c3 Wherein C 1-6 Alkyl, OC 1-6 Alkyl, C 3-6 Cycloalkyl, 3-7-membered heterocycloalkyl, 5-6-membered heteroaryl, and phenyl groups are optionally substituted by one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2; Where R b3 R c3 R d3 and R e3 Choose independently the group consisting of: hydrogen, hydroxyl, C 1-6 Halogenated alkyl, OC 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl and C 6-15 Aryl, wherein the C 1-6 Alkyl, -OC 1-6 Alkyl, C 6-15 Aryl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl; or R d3 and R e3 When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f3 replace; Each R f3 Choose independently the group consisting of the following items: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl; R 4 Choose from the group consisting of: hydroxyl, =O, halogen, -CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, C 6-11 Aryl, 5-11 heteroaryl, -C(=O)R b4 -C(=O)OR c4 -C(=O)NR d4 R e4 -NR d4 R e4 -NR d4 C(=O)R b4 -NR d4 C(=O)OR c4 -NR d4 C(=O)NR d4 R e4 -NR d4 S(=O)2R b4 -NR d4 S(=O)2NR d4 R e4 -OR c4 -SR c4 -OC(=O)R b4 -OC(=O)NR d4 R e4 -OC(=O)OR c4 -S(=O)2R c4 -S(=O)R c4 -OS(=O)R c4 -OS(=O)2R c4 -OS(=O)2OR c4 -S(=O)NR d4 R e4 -OS(=O)2NR d4 R e4 and -S(=O)2NR d4 R e4Wherein C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl and C 6-11 The aryl group may optionally be substituted by one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl, phenyl, -NH2, -NHR' and -NR'R'', wherein R' and R'' are independently selected from C 1-6 Alkyl group, wherein the phenyl group is optionally hydroxyl, halogen, =O, -CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl and -OC 1-6 One or more alkyl groups are substituted; Where R b4 R c4 R d4 and R e4 Choose independently the group consisting of: hydrogen, hydroxyl, C 1-6 Halogenated alkyl groups, -OC 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl and C 6-15 Aryl, wherein the C 1-6 Alkyl, C 6-15 Aryl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl; or R d4 and R e4When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f4 replace; Each R f4 Choose independently the group consisting of the following items: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl; y1, y2, z1, and z2 are integers independently selected from 0, 1, 2, 3, and 4; L is the connector part; and M is the E3 ubiquitin ligase binding site.

[0612] 2. The compound or its salt, solvate or prodrug as described in Project 1, wherein Q is the RIPK1 kinase binding moiety.

[0613] 3. The compound or its salt, solvate or prodrug as described in Project 1 or 2, wherein R 1 Choose the group consisting of the following items: C 3-11 cycloalkyl, C 3-11 cycloalkyl (C 1-3 )alkyl, 3- to 12-membered heterocyclic alkyl, 3- to 12-membered heterocyclic alkyl (C 1-3 )alkyl, C 1-10 Alkyl, C 2-10 alkenyl and C 2-10 Alkyne groups, wherein each is optionally surrounded by one or more R groups a1 replace.

[0614] 4. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R 1 Choose the group consisting of the following items: C 3-7 Cycloalkyl, 3- to 7-membered heterocycloalkyl, C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne groups, wherein each is optionally surrounded by one or more R groups a1 replace.

[0615] 5. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R 1 Choose the group consisting of the following items: C3-7 Cycloalkyl, 3- to 7-membered heterocycloalkyl, C 1-6 Alkyl and C 2-6 Alkyne groups, wherein each is optionally surrounded by one or more R groups a1 replace.

[0616] 6. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R 1 Choose the group consisting of the following items: C 3-7 Cycloalkyl, 3- to 7-membered heterocycloalkyl and C 1-6 Alkyl groups, wherein each is optionally surrounded by one or more R groups a1 replace.

[0617] 7. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R 1 Selected from the following groups, each optionally bound by one or more R groups a1 replace: .

[0618] 8. The compound, salt, solvate, or prodrug of any one of the preceding items, wherein R 1 Selected from the following groups, each optionally bound by one or more R groups a1 replace: .

[0619] 9. The compound, salt, solvate, or prodrug of any one of the preceding items, wherein R 1 Selected from the following groups, each optionally bound by one or more R groups a1 replace: .

[0620] 10. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R 1 It is a cyclohexyl group or an isopropyl group.

[0621] 11. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R a1 Choose independently the group consisting of: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -OC 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=O)R b1 -NR d1 R e1 -OR c1 Wherein C 1-6 Alkyl, OC 1-6 Alkyl, C 3-6 cycloalkyl, -OC 3-6 Cycloalkyl, 3-7-membered heterocycloalkyl, 5-6-membered heteroaryl, and phenyl groups are optionally substituted by one or more groups selected from the following: hydroxyl, halogen, =O, -CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl, phenyl, -C(O)C 1-6 Alkyl, -C(O)N(H)C 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl group 2, -CONH2, -C(O)N(H)C 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl)2、-N(H)C 1-6 Alkyl and -N(C) 1-6 Alkyl)2.

[0622] 12. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R a1 Choose independently the group consisting of: hydroxyl, =O, halogen, CN, CF3, OCF3, C 1-6 Alkyl, OC 1-6 Alkyl, -C(=O)R b1 -NR d1 R e1 and -OR c1 .

[0623] 13. The compound, salt, solvate, or prodrug of any one of the preceding items, wherein R a1 Choose independently the group consisting of: hydroxyl, =O, halogen, CN, CF3, OCF3, C 1-6 Alkyl, OC 1-6 Alkyl, -C(=O)Me, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0624] 14. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R b1 Independently selected from hydrogen and C 3-6 cycloalkyl or C 1-6 alkyl.

[0625] 15. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein each R c1 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 alkyl and phenyl, wherein the C 1-6 Alkyl, phenyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0626] 16. A compound or salt, solvate or prodrug thereof according to any one of the preceding items, wherein each R c1 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, C 3-6 cycloalkyl and C 1-6 Alkyl, wherein the C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0627] 17. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein each R d1 Independently selectable hydrogen and C 3-6 cycloalkyl and C 1-6 The group consisting of alkyl groups, wherein the C1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0628] 18. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein each R e1 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 alkyl and phenyl, wherein the C 1-6 Alkyl, phenyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0629] 19. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein each R e1 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, C 3-6 cycloalkyl and C 1-6 Alkyl, wherein the C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0630] 20. A compound or salt, solvate or prodrug of any one of items 1 to 16, wherein R d1 and R e1 When attached to the same atom, they form a 5-7 membered ring together with the atom to which they are attached, the 5-7 membered ring optionally containing one or more heteroatoms selected from O, N, and S, and wherein the ring is optionally surrounded by one or more R atoms. f1 replace.

[0631] 21. The compound or its salt, solvate or prodrug according to item 20, wherein R f1 Choose from the following groups: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0632] 22. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein A is a cyclic group selected from 5- to 12-membered heteroaryl groups.

[0633] 23. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein A is a 9- or 10-membered fused bicyclic heteroaryl group that suitably contains at least one nitrogen.

[0634] 24. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein A is a cyclic group selected from benzothiazolyl, aza-benzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridyl, imidazopyrazinyl, benzofurazanyl, benzothiadiazinyl, benzothiazinyl, benzoxazolyl, aza-benzoxazolyl, aza-indolyl, zolinyl, furanopyridyl, quinazolinyl, quinoxalinyl and isoquinolinyl.

[0635] 25. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein A is a cyclic group selected from benzothiazolyl, aza-benzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridyl, imidazopyrazinyl, benzoxazolyl, aza-benzoxazolyl, aza-indolyl, cyclolinyl, quinazolinyl, quinoxolinyl and isoquinolinyl.

[0636] 26. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein A is a cyclic group selected from benzothiazolyl, aza-benzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridyl, imidazopyrazinyl, benzoxazolyl, aza-benzoxazolyl and aza-indolyl.

[0637] 27. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein A is a cyclic group selected from benzothiazolyl, aza-benzothiazolyl, benzimidazolyl, aza-benzimidazolyl, imidazopyridyl, imidazopyrazinyl, benzoxazolyl, aza-benzoxazolyl and aza-indolyl.

[0638] 28. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein A is a cyclic group selected from benzothiazolyl, aza-benzothiazolyl, imidazopyrazinyl (suitably imidazo[1,2-a]pyrazinyl) and imidazopyridyl (suitably imidazo[1,2-a]pyridyl).

[0639] 29. A compound or salt, solvate or prodrug thereof according to any one of the preceding items, wherein A is a cyclic group of formula A1. (A1) Where X 1 X 2 X 3 and X 4 Independently selected from C, N, CH or CR 4 The condition is X 1 X 2 X 3 and X 4 Only one of them is C and forms an attachment point with ring B; X 5 and X 6 Independently selected from N or C; X 7 and X 8 Independently selected from O, S, N, CH, CR 4 and NR 4 ; The condition is X 1 X 2 X 3 X 4 X 5 X 6 X 7 and X 8 At least one of them must be N.

[0640] 30. The compound or its salt, solvate or prodrug as described in Item 29, wherein X 8 It is N.

[0641] 31. The compound or its salt, solvate or prodrug as described in item 29 or 30, wherein X 7 It is S or CH.

[0642] 32. A compound or its salt, solvate or prodrug according to any one of items 29 to 31, wherein X 1 X 2 X 3 and X 4 Each of them is C, CH or CR 4 The condition is X 1 X 2 X 3 and X 4 Only one of them is C and forms an attachment point with ring B.

[0643] 33. A compound or a salt, solvate or prodrug thereof according to any one of items 29 to 32, wherein A is a cyclic group of formula A2. (A2) Where X 1 X 2 X 3 and X 4 Independently selected from C, N, CH or CR 4 The condition is X 1 X 2 X 3 and X 4 Only one of them is C and forms an attachment point with ring B.

[0644] 34. The compound or its salt, solvate or prodrug as described in item 33, wherein X 2 It is C and forms an attachment point with ring B, and X 1 X 3 and X 4 Independently selected from N, CH or CR 4 Appropriately, X 1 X 3 and X 4 Independently selected from CH or CR 4 .

[0645] 35. The compound or its salt, solvate or prodrug according to item 29, wherein A is a cyclic group of formula A3. (A3) Where X 11 X12 X 13 and X 14 Independently selected from C, N, CH or CR 4 The condition is X 11 X 12 X 13 and X 14 Only one of them is C and forms an attachment point with ring B.

[0646] 36. The compound or its salt, solvate or prodrug as described in item 35, wherein X 13 It is C and forms an attachment point with ring B, and X 11 X 12 and X 14 Independently selected from N, CH or CR 4 .

[0647] 37. A compound or its salt, solvate, or prodrug as described in item 35 or 36, wherein X 12 It is N or CH, and X 11 and X 14 Independently selected from CH or CR 4 .

[0648] 38. A compound or its salt, solvate or prodrug according to any one of items 1 to 29, wherein A is a cyclic group selected from: , Each of them can be optionally controlled by one or more Rs 4 replace.

[0649] 39. A compound or its salt, solvate or prodrug according to any one of items 1 to 29, wherein A is a cyclic group selected from: , Each of them can be optionally controlled by one or more Rs 4 replace.

[0650] 40. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 29, wherein A is a cyclic group selected from: , Each of them can be optionally controlled by one or more Rs 4 replace.

[0651] 41. A compound or a salt, solvate or prodrug thereof according to any one of items 29 to 40, wherein the wavy line in A or its subform indicates the attachment point with the adjacent group V.

[0652] 42. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein V is selected from the group consisting of: -NH-, -C(O)-, -S(O)2-, -C(O)N(H)-, -N(H)C(O)-, -S(O)(NH)-, -N(H)S(O)-, -S(O)N(H)-, -N(H)S(O)2- and -S(O)2N(H)-.

[0653] 43. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein V is selected from the group consisting of -NH-, -C(O)-, -C(O)N(H)- and -N(H)C(O)-.

[0654] 44. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein V is selected from the group consisting of -NH-, -C(O)N(H)- and -N(H)C(O)-.

[0655] 45. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein V is -NH-.

[0656] 46. ​​A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein Q is Q 1 .

[0657] 47. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein B is selected from 5-membered to 12-membered heteroaryl groups and C 6-11 A ring group of aryl group.

[0658] 48. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein B is a cyclic group selected from 5- to 6-membered heteroaryl and phenyl groups.

[0659] 49. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein B is a 6-membered heteroaryl ring containing one or more nitrogen atoms, or a phenyl group.

[0660] 50. A compound or a salt, solvate or prodrug thereof according to any one of the preceding items, wherein B is a pyridine ring or a phenyl group.

[0661] 51. A compound or salt, solvate or prodrug thereof according to any one of the preceding items, wherein B is a group of formula B1: (B1) Where X 9 and X 10 Independently selected from N and CR 3 Or CH.

[0662] 52. The compound or its salt, solvate or prodrug according to item 51, wherein X 9 It is N.

[0663] 53. A compound or its salt, solvate or prodrug as described in item 51 or 52, wherein X 10 It is CR 3 Or CH.

[0664] 54. A compound or a salt, solvate or prodrug thereof according to any one of items 51 to 53, wherein B is a group of formula B2: (B2)

[0665] 55. A compound or a salt, solvate or prodrug thereof according to any one of items 51 to 54, wherein ring B is .

[0666] 56. A compound or a salt, solvate or prodrug of any one of items 51 to 55, wherein the wavy line indicates the attachment point with the adjacent ring A.

[0667] 57. A compound, salt, solvate, or prodrug according to any one of items 1 to 21, wherein Q has the formula Q 1a : (Q 1a ) in R 2a It is hydrogen or methyl; X 1 X 3 and X 4 Independently selected from N, CH or CR 4 ; X 6 Selected from N or C; X 7 Selected from O, S, N, CH, CR 4 and NR 4 ; X 9 and X 10 Independently selected from N and CR 3 Or CH.

[0668] 58. The compound or its salt, solvate or prodrug as described in item 57, wherein X 6 It is N and X 7 It is CH.

[0669] 59. A compound or its salt, solvate or prodrug according to any one of items 57 to 59, wherein X 10 Is it CH or CR? 3 .

[0670] 60. The compound or its salt, solvate or prodrug as described in item 57, wherein X 6 It is C and X 7 It is S.

[0671] 61. A compound or its salt, solvate or prodrug according to any one of items 57 to 61, wherein X 9 It is N.

[0672] 62. A compound or salt, solvate or prodrug thereof according to any one of items 1 to 21, wherein Q has the formula Q 1d : (Q 1d ) in R 2a It is hydrogen or methyl; X 1 Selected from N, CH or CR 4 ; X 7a It is CH or N; X 9 Selected from N, CR 3 Or CH; and X 10 Selected from N, CR 3 Or CH.

[0673] 63. The compound according to item 62, wherein X 7a It is CH.

[0674] 64. The compound according to item 62 or 63, wherein X 1 Selected from N or CH.

[0675] 65. A compound or a salt, solvate or prodrug thereof according to any one of items 57 to 64, wherein X 10 It is CH and R 2a It is a methyl group.

[0676] 66. A compound or a salt, solvate or prodrug thereof according to any one of items 57 to 64, wherein X 10 It is CMe and R 2a It is hydrogen.

[0677] 67. A compound or salt, solvate or prodrug of any one of items 1 to 21, wherein Q has the formula Q1a : (Q 1c ) in R 2a It is hydrogen or methyl; X 3 Selected from N, CH or CR 4 ; X 9 and X 10 Independently selected from N and CR 3 Or CH.

[0678] 68. The compound or its salt, solvate or prodrug as described in item 67, wherein X 3 It is N or CH.

[0679] 69. A compound or its salt, solvate or prodrug as described in item 67 or 68, wherein X 10 It is CH and R 2a It is a methyl group.

[0680] 70. A compound or its salt, solvate, or prodrug as described in item 67 or 68, wherein X 10 It is CMe and R 2a It is hydrogen.

[0681] 71. A compound, salt, solvate, or prodrug according to any one of items 1 to 21, wherein Q has the formula Q 1b : (Q 1b ), Where R 2a It is hydrogen or methyl, preferably hydrogen.

[0682] 72. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R 3 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cycloalkyl, -C(=O)R b3 -C(=O)OR c3 -C(=O)NR d3 R e3 -NR d3 R e3 -NR d3C(=O)R b3 -OR c3 -SR c3 Wherein C 1-6 Alkyl, OC 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0683] 73. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R 3 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -NR d3 R e3 -OR c3 -SR c3 Wherein C 1-6 Alkyl, OC 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0684] 74. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R 3 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C2-6 alkynyl, -NR d3 R e3 Wherein C 1-6 Alkyl and OC 1-6 The alkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0685] 75. A compound or salt, solvate or prodrug of any one of the preceding items, wherein R 3 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0686] 76. A compound, salt, solvate, or prodrug according to any one of the preceding items, wherein R 3 Choose from the group consisting of: hydroxyl, =O, Cl, Br, CN, CF3, OCF3, methyl, ethyl, and OMe.

[0687] 77. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein each R b3 Independently selected from hydrogen and C 3-6 cycloalkyl or C 1-6 alkyl.

[0688] 78. A compound or salt, solvate or prodrug thereof according to any one of the preceding items, wherein each R c3 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 alkyl and phenyl, wherein the C 1-6 Alkyl, phenyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0689] 79. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein each R c3 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, C 3-6 cycloalkyl and C 1-6 Alkyl, wherein the C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0690] 80. The compound according to any one of the foregoing items, each R d3 Independently selected from hydrogen or C 1-6 alkyl.

[0691] 81. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein each R e3 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 alkyl and phenyl, wherein the C 1-6 Alkyl, phenyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0692] 82. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein each R e3 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, C 3-6 cycloalkyl and C 1-6 Alkyl, wherein the C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0693] 83. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein each R e3 Independently selected from hydrogen or C 1-6 alkyl.

[0694] 84. A compound or salt, solvate or prodrug of any one of items 1 to 79, wherein R d3 and R e3 When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f3 replace.

[0695] 85. The compound or its salt, solvate or prodrug as described in item 84, wherein R f3 Choose from the following groups: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 1-6 Alkyl and -OC 1-6 Alkyl group. In another embodiment, R f3 Selected from hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-4 Alkyl, -N(C)1-4 Alkyl)2, C 1-4 Haloalkyl, C 1-4 Alkyl and -OC 1-4 alkyl.

[0696] 86. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein y1 is an integer selected from 0, 1 and 2.

[0697] 87. A compound or salt, solvate or prodrug thereof according to any one of items 1 to 45, wherein Q is of formula Q 2 protein binding portion (Q 2 ).

[0698] 88. The compound of claim 87 or a salt, solvate or prodrug thereof, wherein C is a 5- to 12-membered heterocycle containing at least one nitrogen atom in the ring, and wherein -COOR 1 Part of it is bonded to the ring C via nitrogen atoms in the ring C.

[0699] 89. A compound or its salt, solvate or prodrug according to item 87 or 88, wherein C is an 8- to 12-membered heterocycle containing at least one nitrogen atom in the ring, and wherein -COOR 1 Part of it is bonded to the ring C via nitrogen atoms in the ring C.

[0700] 90. A compound or a salt, solvate or prodrug of any one of items 87 to 88, wherein C is a 9- or 10-membered heterocycle containing at least one nitrogen atom in the ring, and wherein -COOR 1 Part of it is bonded to the ring C via nitrogen atoms in the ring C.

[0701] 91. The compound or its salt, solvate or prodrug according to any one of items 87 to 90, wherein in another embodiment, C is a 9- or 10-membered fused bicyclic heterocycle containing at least one nitrogen atom in the ring, and wherein -COOR 1 Part of it is bonded to the ring C via nitrogen atoms in the ring C.

[0702] 92. A compound or a salt, solvate or prodrug thereof according to any one of items 87 to 91, wherein C has the formula C1: (C1) in Dashed line indicates -COOR 1 Attachment point; X 12 X 13 and X 14Independently selected from N and CR 9 Or CH; X 15 It is CH2, CHR 9 C(R) 9 2. NH, NR 9 S, S(O), S(O)2 or O; and n C It is an integer selected from 0, 1, or 2.

[0703] 93. The compound or its salt, solvate or prodrug as described in item 92, wherein X 15 It is O, CH2, or NMe.

[0704] 94. A compound or its salt, solvate, or prodrug as described in item 92 or 93, wherein X 14 It is N.

[0705] 95. A compound or its salt, solvate or prodrug according to any one of items 92 to 94, wherein X 12 and X 13 It is CH.

[0706] 96. A compound or its salt, solvate or prodrug according to any one of items 92 to 95, wherein n C It is an integer selected from 0 or 1.

[0707] 97. A compound or a salt, solvate or prodrug thereof according to any one of items 87 to 96, wherein C is selected from: , Each of them can be arbitrarily assigned to R 9 replace.

[0708] 98. A compound or a salt, solvate or prodrug thereof according to any one of items 87 to 97, wherein C is selected from: , Each of them can be arbitrarily assigned to R 9 replace.

[0709] 99. A compound or its salt, solvate or prodrug according to any one of items 87 to 98, wherein C is selected from: Each of them can be arbitrarily assigned to R 9 replace.

[0710] 100. A compound or a salt, solvate or prodrug thereof according to any one of items 87 to 99, wherein C is selected from: , Each of them can be arbitrarily assigned to R 9 replace.

[0711] 101. The compound or its salt, solvate or prodrug as described in Item 87, wherein Q 2 With sub-Q 2a : (Q 2a ) in X 1 X 3 and X 4 Independently selected from N, CH or CR 4 ; X 6 Selected from N or C; X 7 Selected from O, S, N, CH, CR 4 and NR 4 ; X 15 Selected from CH2, CHR 9 C(R) 9 2. NH, NR 9 S, S(O), S(O)2 or O.

[0712] 102. The compound or its salt, solvate or prodrug as described in item 101, wherein X 6 It is N and X 7 It is CH.

[0713] 103. The compound or its salt, solvate or prodrug as described in item 101 or 102, wherein X 1 X 3 and X 4 Is it CH or CR? 4 .

[0714] 104. The compound or its salt, solvate or prodrug according to item 101, wherein X 6 It is C and X 7 It is S.

[0715] 105. A compound or its salt, solvate or prodrug according to any one of items 101 to 104, wherein X 15 It is O, NMe, or CH.

[0716] 106. The compound or its salt, solvate or prodrug as described in Item 87, wherein Q 2 With sub-Q 2b : (Q2b ) in X 1 X 3 and X 4 Independently selected from N, CH or CR 4 ; X 6 Selected from N or C; X 7 Selected from O, S, N, CH, CR 4 and NR 4 .

[0717] 107. The compound or its salt, solvate or prodrug as described in item 106, wherein X 6 It is N and X 7 It is CH.

[0718] 108. The compound or its salt, solvate or prodrug as described in item 106, wherein X 6 It is C and X 7 It is S.

[0719] 109. A compound or its salt, solvate or prodrug according to any one of items 106 to 108, wherein X 1 X 3 and X 4 Is it CH or CR? 4 .

[0720] 110. The compound or its salt, solvate or prodrug as described in Item 87, wherein Q 2 With sub-Q 2c : (Q 2c ) Where X 15 Selected from CH2, CHR 9 C(R) 9 2. NH, NR 9 S, S(O), S(O)2 or O.

[0721] 111. The compound or its salt, solvate or prodrug as described in item 110, wherein X 15 Selected from O, NMe, or CH.

[0722] 112. The compound or its salt, solvate or prodrug as described in Item 87, wherein Q 2 With sub-Q 2d : (Q 2d ).

[0723] 113. The compound or its salt, solvate or prodrug as described in Item 87, wherein Q 2 With sub-Q 2e : (Q 2e ) Where X 15 Selected from CH2, CHR 9 C(R) 9 2. NH, NR 9 S, S(O), S(O)2 or O; X 7b Selected from CH or N; and X 1 Selected from N, CH or CR 4 .

[0724] 114. The compound or its salt, solvate or prodrug as described in item 113, wherein X 15 Selected from O, NMe, or CH.

[0725] 115. The compound or its salt, solvate or prodrug as described in Item 87, wherein Q 2 With sub-Q 2e : (Q 2f ) Where X 7b Selected from CH or N; and X 1 Selected from N, CH or CR 4 .

[0726] 116. A compound or its salt, solvate or prodrug according to any one of items 113 or 115, wherein X 1 Selected from N or CH.

[0727] 117. A compound or salt, solvate or prodrug thereof according to any one of items 113 to 116, wherein X 7b Selected from CH.

[0728] 118. A compound, salt, solvate, or prodrug according to any one of the preceding items, wherein R 4 Selected from hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6Cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=O)R b3 -C(=O)OR c4 -C(=O)NR d4 R e4 -NR d4 R e4 -NR d4 C(=O)R b4 -OR c4 -SR c4 Wherein C 1-6 Alkyl, OC 1-6 Alkyl, C 3-6 Cycloalkyl, 3-7-membered heterocycloalkyl, 5-6-membered heteroaryl, and phenyl groups are optionally substituted by one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0729] 119. A compound, salt, solvate, or prodrug according to any one of the preceding items, wherein R 4 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cycloalkyl, -C(=O)R b4 -C(=O)OR c4 -C(=O)NR d4 R e4 -NR d4 R e4 -NR d4 C(=O)R b4 -OR c4 -SR c4 Wherein C 1-6 Alkyl, OC 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0730] 120. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R 4 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -NR d4 R e4 -OR c4 -SR c4 Wherein C 1-6 Alkyl, OC 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0731] 121. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R 4 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -NR d4 R e4 Wherein C 1-6 Alkyl and OC 1-6 The alkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0732] 122. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R 4 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0733] 123. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R 4 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 1-4 Alkyl, OC 1-4 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0734] 124. A compound or salt, solvate or prodrug thereof according to any one of the preceding items, wherein R 4 Choose from the group consisting of: hydroxyl, =O, Cl, Br, CN, CF3, OCF3, methyl, ethyl, and OMe.

[0735] 125. A compound, salt, solvate, or prodrug according to any one of the preceding items, wherein R b4 Independently selected from hydrogen and C 3-6 cycloalkyl or C 1-6 alkyl.

[0736] 126. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein each R c4 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 alkyl and phenyl, wherein the C 1-6 Alkyl, phenyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0737] 127. A compound, salt, solvate, or prodrug according to any one of the preceding items, wherein R c4 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, C 3-6 cycloalkyl and C 1-6 Alkyl, wherein the C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0738] 128. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein each R d4 Independently selectable hydrogen and C 3-6 cycloalkyl and C 1-6 The group consisting of alkyl groups, wherein the C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0739] 129. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein each R e4Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 alkyl and phenyl, wherein the C 1-6 Alkyl, phenyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0740] 130. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein each R e4 Choose independently the group consisting of the following items: hydrogen, C 1-6 Haloalkyl, C 3-6 cycloalkyl and C 1-6 Alkyl, wherein the C 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl group. In another embodiment, each R e4 Independently selected from hydrogen or C 1-6 alkyl.

[0741] 131. A compound or salt, solvate or prodrug thereof according to any one of items 1 to 119, wherein R d4 and R e4 When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f4 replace.

[0742] 132. The compound or its salt, solvate or prodrug as described in item 123, wherein Rf4 Choose from the following groups: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 1-6 Alkyl and -OC 1-6 alkyl.

[0743] 133. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein z1 is an integer selected from 0, 1 and 2.

[0744] 134. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R 9 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cycloalkyl, -C(=O)R b3 -C(=O)OR c3 -C(=O)NR d3 R e3 -NR d3 R e3 -NR d3 C(=O)R b3 -OR c3 -SR c3 Wherein C 1-6 Alkyl, OC 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0745] 135. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R 9 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -NR d3 R e3 -OR c3 -SR c3 Wherein C 1-6 Alkyl, OC 1-6 Alkyl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0746] 136. A compound or salt, solvate or prodrug thereof according to any one of the preceding items, wherein R 9 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -NR d3 R e3 Wherein C 1-6 Alkyl and OC 1-6 The alkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0747] 137. A compound, salt, solvate, or prodrug according to any one of the preceding items, wherein R 9 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0748] 138. A compound or salt, solvate or prodrug thereof according to any one of the preceding items, wherein R 9 Choose from the following groups: hydroxyl, =O, halogen, CN, C 1-3 Haloalkyl, C 1-3 Halogenated alkoxy groups, C 1-4 Alkyl, OC 1-4 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2.

[0749] 139. A compound or salt, solvate or prodrug thereof according to any one of the preceding items, wherein R 9 Choose from the group consisting of: hydroxyl, =O, Cl, Br, CN, CF3, OCF3, methyl, ethyl, and OMe.

[0750] 140. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein R 9 Choose from the group consisting of: hydroxyl, =O, methyl, ethyl, and OMe.

[0751] 141. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein y2 is an integer selected from 0, 1 and 2.

[0752] 142. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein z2 is an integer selected from 0, 1 and 2. In another embodiment, z2 is 1. In another embodiment, z2 is 0.

[0753] 143. A compound or its salt, solvate or prodrug according to any one of the preceding items, wherein L is the connecting part of formula L1: L appears each time a Independently selected from -S-, -S(=O)-, -S(=O)2-, -O-, -C(=O-), -C(=O)O-, -OC(=O-), -CR 5 R 6 -、-CR 5 =CR 6 -、-C≡C-、-NR 5-、-NR 5 C(=O)-、-C(=O)NR 5 -、-OC(=O)NR 5 -、-NR 5 C(=O)NR 6 -、-NR 5 C(=O)O-、-NR 5 S(O)NR 6 -、-OC(R 5 (R) 6 )C(R 5 (R) 6 )-、-S(=O)2NR 5 -、-NR 5 S(=O)2-、C3-C 13 cycloalkyl, C6-C 11 aryl, 5- to 11-membered heteroaryl and 3- to 11-membered heterocycloalkyl, wherein the C3-C 13 cycloalkyl, C6-C 11 aryl, 5- to 11-membered heteroaryl and 3- to 11-membered heterocyclic alkyl groups are optionally separated by one or more R groups. 7 replace; n1 is a value from 1 to 50; and R 5 R 6 and R 7 Each time it appears, independently select the group consisting of the following items: hydrogen, hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups, phenyl groups, 5-6-membered heteroaryl groups, 3- to 7-membered heterocyclic alkyl groups, and C 3-6 Cycloalkyl groups, each of which may optionally be substituted with one or more groups selected from the following: C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, phenyl, and hydroxyl.

[0754] 144. The compound or its salt, solvate or prodrug as described in item 143, wherein n1 is a value of 3 to 40, or 3 to 30, or 3 to 20, or 3 to 15, or 3 to 10.

[0755] 145. The compound or its salt, solvate or prodrug as described in item 143 or 144, wherein L a Independently selected from -S-, -S(=O)-, -S(=O)2-, -O-, -C(=O)-, -CR 5 R 6 -、-NR 5-、-NR 5 C(=O)-、-C(=O)NR 5 -、-OC(R 5 (R) 6 )C(R 5 (R) 6 )-、-S(=O)2NR 5 -、-NR 5 S(=O)2-、C3-C 13 cycloalkyl, C6-C 11 aryl, 5- to 11-membered heteroaryl and 3- to 11-membered heterocycloalkyl, wherein the C3-C 13 cycloalkyl, C6-C 11 aryl, 5- to 11-membered heteroaryl and 3- to 11-membered heterocyclic alkyl groups are optionally separated by one or more R groups. 7 Replace; or Each L a Independently selected from -O-, -C(=O)-, -CR 5 R 6 -、-NR 5 -、-NR 5 C(=O)-、-C(=O)NR 5 -、-OC(R 5 (R) 6 )C(R 5 (R) 6 )-、C3-C 13 cycloalkyl, C6-C 11 aryl, 5- to 11-membered heteroaryl and 3- to 11-membered heterocycloalkyl, wherein the C3-C 13 cycloalkyl, C6-C 11 aryl, 5- to 11-membered heteroaryl and 3- to 11-membered heterocyclic alkyl groups are optionally separated by one or more R groups. 7 Replace; or Each L a Independently selected from -O-, -C(=O)-, -CR 5 R 6 -、-NR 5 -、-NR 5 C(=O)-、-C(=O)NR 5 -、-OC(R 5 (R) 6 )C(R 5 (R) 6 )-、C3-C 13 Cycloalkyl, 5- to 11-membered heteroaryl and 3- to 11-membered heterocycloalkyl, wherein the C3-C 13 cycloalkyl, C6-C 11aryl, 5- to 11-membered heteroaryl and 3- to 11-membered heterocyclic alkyl groups are optionally separated by one or more R groups. 7 replace.

[0756] 146. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L2: in L b1 and L b2 Independently does not exist or is freely chosen -C(=O)-, -NR 5 C(=O)- and -C(=O)NR 5 -A group; L d1 and L d2 Independently does not exist or is chosen freely from C3-C 13 The group consisting of cycloalkyl, phenyl, 5- to 6-membered heteroaryl and 3- to 10-membered heterocycloalkyl, wherein the C3-C 13 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl and 3- to 10-membered heterocycloalkyl are optionally separated by one or more R 7 replace; Each L c Independently select from the following groups: -CR 5 R 6 -、-O-、-OC(R 5 (R) 6 )C(R 5 (R) 6 -, -C(=O)-, -NR 5 -、-NR 5 C(=O)-、-C(=O)NR 5 - 5-6-membered heteroaryl and 5-6-membered heterocyclic alkyl, wherein the 5-6-membered heteroaryl and 5-6-membered heterocyclic alkyl are optionally represented by one or more R 7 replace; n2 is a value between 0 and 20; and R 5 R 6 and R 7 Each time it appears, independently select the group consisting of the following items: hydrogen, hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups, phenyl groups, 5-6-membered heteroaryl groups, 3- to 7-membered heterocyclic alkyl groups, and C 3-6 Cycloalkyl groups, each of which may optionally be substituted with one or more groups selected from the following: C 1-4 Alkyl, C1-4 Alkoxy, C 3-6 Cycloalkyl, phenyl, and hydroxyl.

[0757] 147. The compound or its salt, solvate or prodrug as described in item 146, wherein L b1 and L b2 It does not exist independently or is -C(=O)-.

[0758] 148. The compound or its salt, solvate or prodrug as described in item 146 or 147, wherein L d1 and L d2 Independently does not exist or is selected freely from C5-C 10 The group consisting of cycloalkyl, phenyl, 5- to 6-membered heteroaryl and 5- to 10-membered heterocycloalkyl, wherein the C5-C 10 Cycloalkyl, phenyl, 5- to 6-membered heteroaryl and 5- to 10-membered heterocycloalkyl are optionally separated by one or more R 7 replace.

[0759] 149. The compound or its salt, solvate or prodrug according to any one of items 146 to 148, wherein L d1 and L d2 Independently absent or selected from the group consisting of C5-C8 cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 5- to 8-membered heterocycloalkyl, wherein the C5-C8 cycloalkyl, phenyl, 5- to 6-membered heteroaryl, and 5- to 8-membered heterocycloalkyl are optionally represented by one or more R 7 replace.

[0760] 150. The compound or its salt, solvate or prodrug according to any one of items 146 to 149, wherein each L c Independently select from the following groups: -CR 5 R 6 -、-O-、-OC(R 5 (R) 6 )C(R 5 (R) 6 -, -C(=O)-, -NR 5 -、-NR 5 C(=O)-、-C(=O)NR 5 - and 5-6 membered heterocyclic alkyl groups, wherein the 5-6 membered heterocyclic alkyl group is optionally composed of one or more R groups. 7 replace.

[0761] 151. The compound or its salt, solvate or prodrug according to any one of items 146 to 150, wherein L c Independently select from the following groups: -CR 5R 6 -、-O-、-OC(R 5 (R) 6 )C(R 5 (R) 6 -, -C(=O)-, -NR 5 - and 5-6 membered heterocyclic alkyl groups, wherein the 5-6 membered heterocyclic alkyl group is optionally composed of one or more R groups. 7 replace.

[0762] 152. The compound or its salt, solvate or prodrug according to any one of items 146 to 151, wherein L c Independently select from the following groups: -CR 5 R 6 -、-O-、-OC(R 5 (R) 6 )C(R 5 (R) 6 )- and 5-6-membered heterocyclic alkyl groups, wherein the 5-6-membered heterocyclic alkyl group is optionally composed of one or more R 7 replace.

[0763] 153. The compound or its salt, solvate or prodrug according to any one of items 146 to 152, wherein L c Independently selected from the group consisting of: -CH2-, -O-, -OCH2CH2- and 5-6-membered heterocyclic alkyl groups, wherein the 5-6-membered heterocyclic alkyl group is optionally separated by one or more R groups. 7 replace.

[0764] 154. The compound or its salt, solvate or prodrug according to any one of items 146 to 153, wherein each L c Choose independently the group consisting of -CH2-, -O-, and -OCH2CH2-.

[0765] 155. The compound or its salt, solvate or prodrug according to any one of items 146 to 154, wherein n2 is a value from 0 to 12.

[0766] 156. The compound or its salt, solvate or prodrug according to any one of items 146 to 155, wherein n2 is a number from 4 to 10.

[0767] 157. A compound or salt, solvate or prodrug thereof according to any one of items 143 to 156, wherein R 5 It is either hydrogen or methyl.

[0768] 158. A compound or salt, solvate or prodrug thereof according to any one of items 143 to 157, wherein R6 It is either hydrogen or methyl.

[0769] 159. A compound or salt, solvate or prodrug thereof according to any one of items 143 to 158, wherein R 7 Each time it appears, it is independently selected from hydroxyl, =O, and C. 1-4 A group composed of alkyl groups.

[0770] 160. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L3: (L3), Where n4 is an integer value from 0 to 20.

[0771] 161. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L4: (L4), Where n4a is an integer value from 0 to 20.

[0772] 162. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L5: (L5), Where n3 is a value from 1 to 10, and each n5 is an independent integer value from 0 to 5.

[0773] 163. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is a linking part selected from: ; ;and .

[0774] 164. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L6: (L6), Where n3 is a value from 1 to 10, and each n5 is an independent integer value from 0 to 5.

[0775] 165. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L7: (L7), Where n12 is a value between 2 and 10.

[0776] 166. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is a linking part selected from: ; .

[0777] 167. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L8: (L8), Where n6 is an integer value from 0 to 10, n7 is a value from 1 to 12; n19 is an integer value of 0 or 1; and the ring D is optionally bounded by one or more R... 7 Substituted phenyl or 6-membered heteroaryl ring.

[0778] 168. The compound or its salt, solvate or prodrug as described in item 167, wherein D is phenyl or pyridyl.

[0779] 169. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is a linking part selected from: ; ; ; ; ; .

[0780] 170. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L9: (L9), Where n8 is a value from 1 to 12.

[0781] 171. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L10: (L10), Where n11 is an integer value from 0 to 12, and the ring E is optionally bounded by one or more R... 7 Substituted phenyl or 6-membered heteroaryl ring.

[0782] 172. The compound or its salt, solvate or prodrug as described in item 171, wherein ring E is phenyl, pyridyl or pyridone.

[0783] 173. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is a linking part selected from: ; .

[0784] 174. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L11: (L11) Each of n12 and n13 is an independent integer value from 0 to 5, and the ring F is optionally bounded by one or more R... 7 Substituted 5- or 6-membered heterocyclic alkyl rings.

[0785] 175. The compound or its salt, solvate or prodrug according to item 174, wherein ring F is a 6-membered heterocyclic alkyl ring, suitably selected from piperazine or piperidinyl.

[0786] 176. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L11a: (L11a); Where ring K1 can be arbitrarily divided by one or more R... 24 Substituted 5- to 10-membered heterocyclic alkyl rings; n40 is an integer value from 0 to 8; n41 is an integer value from 0 to 8; R 24 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0787] 177. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting portion of formula L11b: (L11b); Where ring K2 can be arbitrarily divided by one or more R... 25 Substituted 5- to 10-membered heterocyclic alkyl rings; n42 is an integer value from 0 to 8; n43 is an integer value from 0 to 8; n44 and n45 are independently selected from integer values ​​0 to 5; and R 25 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0788] 178. A compound or salt thereof, solvate thereof, or prodrug according to any one of items 1 to 142, wherein L is selected from: ; .

[0789] 179. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L11c: (L11c); Where ring K3 can be arbitrarily divided by one or more R... 27 Substituted 4- to 10-membered heterocyclic alkyl rings; n47 is an integer value from 0 to 3; n48 is selected from integer values ​​0 to 5; n49 is an integer value of 0 or 1; R 12 and R 13 Independently selected from H, halogen, C 1-4 Alkyl, C 3-6 cycloalkyl; or R 12 and R 13 Together with the carbon atoms to which they are attached, they form C 3-6 cycloalkyl groups; and R 27 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0790] 180. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L12: (L12) Each n14 and n15 is independently an integer value from 0 to 5, and ring G and ring H are independently selected from the group consisting of: 5- to 7-membered heterocyclic alkyl, 5- or 6-membered heteroaryl, and C3-C. 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 7 replace.

[0791] 181. The compound or its salt, solvate or prodrug according to item 180, wherein ring G is selected from the group consisting of 5- to 7-membered heterocyclic alkyl groups and C3-C4 groups. 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 7 replace.

[0792] 182. The compound or its salt, solvate or prodrug according to item 180 or 181, wherein the ring H is optionally surrounded by one or more R... 7 Replaced 5- to 6-membered heteroaryl groups.

[0793] 183. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L13: (L13); Where n16 is an integer value of 0 or 1, and n17 is a value from 1 to 12.

[0794] 184. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L14a: (L14a); Where n18 is a number from 1 to 5, and ring G1 and ring H1 are independently selected from the group consisting of: 5- to 7-membered heterocyclic alkyl, 5- or 6-membered heteroaryl, and C3-C 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 7 replace.

[0795] 185. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L14b: (L14b); Where n20 is a value from 1 to 5; Where n21 and n27 are independent integer values ​​0 or 1; The ring G2 and ring H2 are independently selected from the group consisting of: 4- to 10-membered heterocyclic alkyl groups, 5- or 6-membered heteroaryl groups, and C3-C. 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 8 replace; R 8 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; and R 10 and R 11 Independently selected from H and C 1-4 Alkyl, C 3-6 cycloalkyl; or R 10 and R 11 Together with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups.

[0796] 186. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L14c: (L14c); Where n23 is an integer value of 0 or 1; n24 is an integer value from 0 to 3; The ring G3 and ring H3 are independently selected from the group consisting of: 4- to 10-membered heterocyclic alkyl groups, 5- or 6-membered heteroaryl groups, and C3-C. 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 8c replace; R 8c Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; and R 12c and R 13c Independently selected from H, halogen, C 1-4 Alkyl, C 3-6 cycloalkyl; or R 12c and R 13c Together with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups.

[0797] 187. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L14d: (L14d); Where n26 is an integer value of 0 or 1; n28 is an integer value of 0, 1, or 2; Z does not exist or is selected from NH, N(C) 1-3 Alkyl), O, or S groups; The ring G4 and ring H4 are independently selected from the group consisting of: 4- to 10-membered heterocyclic alkyl groups, 5- or 6-membered heteroaryl groups, and C3-C4 groups. 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 8d replace; R 8d Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; R 10d and R 11d Independently selected from H and C 1-4 Alkyl, C 3-6 cycloalkyl; or R 10d and R 11d Together with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups; R 12d and R 13d Independently selected from H, halogen, C 1-4 Alkyl, C 3-6 cycloalkyl; or R 12d and R 13dTogether with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups.

[0798] 188. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L14e: (L14e); Where n50 and n51 are independent integer values ​​0 or 1; n52 and n53 are independent integer values ​​of 0, 1 or 2; Cycle G5, cycle H5, and cycle D5 are independently selected from the group consisting of: 4- to 10-membered heterocyclic alkyl groups, 5- or 6-membered heteroaryl groups, and C3-C... 10 Cycloalkyl groups, each optionally consisting of one or more R groups. 8e replace; R 8e Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; and R 10e and R 11e Independently selected from H and C 1-4 Alkyl, C 3-6 cycloalkyl; or R 10e and R 11e Together with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups; R 12e and R 13e Independently selected from H, halogen, C 1-4 Alkyl, C 3-6 cycloalkyl; or R 12e and R 13e Together with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups.

[0799] 189. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L15: (L15), Wherein ring D1 is a 5- or 6-membered heteroaryl ring or a phenyl ring, each of which may optionally be surrounded by one or more R groups. 20 replace; n30 is an integer value from 0 to 5; n31 is a value from 1 to 12; and n32 is an integer value of 0 or 1; and R 20 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0800] 190. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting part of formula L16: (L16); Where ring J can be arbitrarily divided by one or more R. 23 Substituted 5- to 10-membered heterocyclic alkyl rings; n33 is an integer value from 0 to 5; n34 is a value from 1 to 12; and n35 is an integer value of 0 or 1; and R 23 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0801] 191. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting portion of formula L16a: (L16a); Where ring J1 can be arbitrarily divided by one or more Rs 26 Substituted 4- to 10-membered heterocyclic alkyl rings; Z 1 It does not exist or is selected from NH, N(C) 1-3 Alkyl), O, or S groups; n37 and n38 are independently selected from integer values ​​0 to 5; and n36 and n39 are independently selected from integer values ​​0 or 1; and R 26 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0802] 192. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is the connecting portion of formula L16b: (L16b); Where ring J2 can be arbitrarily divided by one or more Rs 26b Substituted 4- to 10-membered heterocyclic alkyl rings; Z 2 It does not exist or is selected from NH, N(C) 1-3 Alkyl), O, or S groups; n57 and n58 are independently selected from integer values ​​0 to 5; and n56 and n59 are independently selected from integer values ​​0 or 1; and R 26b Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups and C 3-6 Cycloalkyl groups, each optionally composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

[0803] 193. A compound or a salt, solvate or prodrug thereof according to any one of Items 1 to 142, wherein L is a connector according to one of Formula L3, Formula L4, Formula L5, Formula L11, Formula L11b, Formula L11c, Formula L13, Formula L14a, Formula L14b, Formula L14c, Formula L14d, Formula L14e, Formula L15, Formula L16 and Formula L16a.

[0804] 194. A compound or a salt, solvate or prodrug thereof according to any one of Items 1 to 142, wherein L is a connector according to one of Formula L3, Formula L4, Formula L11b, Formula L11c, Formula L13, Formula L14b, Formula L14c, Formula L14d, Formula L15, Formula L16 and Formula L16a.

[0805] 195. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is .

[0806] 196. A compound or salt, solvate or prodrug thereof according to any one of items 1 to 142, wherein L is .

[0807] 197. A compound or its salt, solvate or prodrug according to any one of items 1 to 142, wherein L is .

[0808] 198. The compound or its salt, solvate or prodrug according to any one of the preceding items, wherein M is an E3 ubiquitin ligase binding moiety capable of binding to the Hippel-Lindau (VHL) ligase.

[0809] 199. A compound or a salt, solvate or prodrug thereof according to any one of the preceding items, wherein M is the E3 ubiquitin ligase-binding moiety of formula M1: (M1); in R M1a It can be optionally converted by halogens, -OH, -O(C) 1-4 alkyl), -S(C 1-4 alkyl) substituted C 2-6 alkyl groups; R M1b Selected from hydrogen or optionally converted by -C(O)N(H)Me, -OH, -NH2, -NH(C 1-4 alkyl), -N(C) 1-4 C-substituted with alkyl groups, -CO2Et, and -COOH 1-6 Alkyl; and R M1c Choose from the following groups: halogens, -NO2, -CN, C 2-4 Alkyne, 5-6 heteroaryl, and phenyl, wherein the 5-6 heteroaryl and phenyl groups are optionally selected from one or more halogens and C. 1-3 Alkyl groups are substituted.

[0810] 200. The compound or its salt, solvate or prodrug as described in item 199, wherein R M1a It is C 3-6 Alkyl groups, preferably isopropyl or tert-butyl groups.

[0811] 201. The compound or its salt, solvate or prodrug as described in item 199 or 200, wherein R M1b Selected from hydrogen or methyl, suitably ( S )-methyl.

[0812] 202. A compound or a salt, solvate or prodrug thereof according to any one of items 199 to 201, wherein R M1c It is a 5-6-membered heteroaryl and phenyl group, wherein the 5-6-membered heteroaryl and phenyl group is optionally selected from one or more halogens and C. 1-3 Alkyl groups are substituted.

[0813] 203. A compound or a salt, solvate or prodrug thereof according to any one of items 199 to 202, wherein R M1c It is optionally selected by one or more halogens and C 1-3 A 5-membered heteroaryl group substituted with an alkyl group. Suitablely, R M1c It is optionally selected by one or more halogens and C 1-3 Thiazoles or oxazoles with alkyl groups substituted.

[0814] 204. A compound or a salt, solvate or prodrug thereof according to any one of items 199 to 203, wherein R M1c Selected from: .

[0815] 205. A compound or its salt, solvate or prodrug according to any one of items 1 to 198, wherein M is , Where R M1b Is it H or ( S )-methyl.

[0816] 206. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 198, wherein M is the E3 ubiquitin ligase-binding moiety of formula M2: (M2); in R M2a It can be optionally converted by halogens, -OH, -O(C) 1-4 alkyl), -S(C 1-4 alkyl) substituted C 2-6 alkyl groups; R M2d Selected from: ; R M2b Selected from hydrogen or optionally converted by -C(O)N(H)Me, -OH, -NH2, -NH(C 1-4 alkyl), -N(C) 1-4 C-substituted with alkyl groups, -CO2Et, and -COOH 1-6 Alkyl; and R M2c Choose from the following groups: halogens, -NO2, -CN, C 2-4 Alkyne, 5-6 heteroaryl, and phenyl, wherein the 5-6 heteroaryl and phenyl groups are optionally selected from one or more halogens and C. 1-3 Alkyl groups are substituted.

[0817] 207. The compound or its salt, solvate or prodrug according to item 206, wherein R M2a It is C 3-6 Alkyl groups, suitable isopropyl groups or tert-butyl groups, suitable ( S )-isopropyl group or ( S )-tert-butyl group.

[0818] 208. The compound or its salt, solvate or prodrug as described in item 206 or 207, wherein R M2b Selected from hydrogen or methyl.

[0819] 209. A compound or a salt, solvate or prodrug thereof according to any one of items 206 to 208, wherein R M2d Selected from: .

[0820] 210. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 198, wherein M is the E3 ubiquitin ligase-binding moiety of the following formula: , where R M2e It is F or CN, and R M2b It is H or methyl.

[0821] 211. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 198, wherein M is the E3 ubiquitin ligase-binding moiety of the following formula: .

[0822] 212. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 198, wherein M is the E3 ubiquitin ligase-binding moiety of formula M3: (M3); in R M3a It can be optionally converted by halogens, -OH, -O(C) 1-4 alkyl), -S(C 1-4 alkyl) substituted C 2-6 alkyl groups; R M3d Selected from: ; R M3c Choose from the following groups: halogens, -NO2, -CN, C 2-4 Alkyne, 5-6 heteroaryl, and phenyl, wherein the 5-6 heteroaryl and phenyl groups are optionally selected from one or more halogens and C. 1-3 Alkyl groups are substituted.

[0823] 213. The compound or its salt, solvate or prodrug as described in item 212, wherein R M3a It is C 3-6 Alkyl groups, suitable isopropyl groups or tert-butyl groups, suitable ( S )-isopropyl group or ( S )-tert-butyl group.

[0824] 214. The compound or its salt, solvate or prodrug as described in item 212 or 213, wherein R M3d Selected from: .

[0825] 215. A compound or a salt, solvate or prodrug thereof according to any one of items 212 to 214, wherein R M3c It is a 5-6-membered heteroaryl and phenyl group, wherein the 5-6-membered heteroaryl and phenyl group is optionally selected from one or more halogens and C. 1-3 Alkyl groups are substituted.

[0826] 216. A compound or salt, solvate or prodrug of any one of items 212 to 215, wherein R M3c It is optionally selected by one or more halogens and C 1-3 A 5-membered heteroaryl group substituted with an alkyl group. Suitablely, R M1c It is optionally selected by one or more halogens and C 1-3 Thiazoles or oxazoles with alkyl groups substituted.

[0827] 217. A compound or a salt, solvate or prodrug thereof according to any one of items 212 to 216, wherein R M3c Selected from: .

[0828] 218. A compound or its salt, solvate or prodrug according to any one of items 1 to 198, wherein M is .

[0829] 219. A compound or a salt, solvate or prodrug thereof according to any one of items 1 to 198, wherein M is the E3 ubiquitin ligase-binding moiety of formula M6: (M6); in R M6a It can be optionally converted by halogens, -OH, -O(C) 1-4 alkyl), -S(C 1-4 alkyl) substituted C 2-6 alkyl groups; R M6b Selected from hydrogen or optionally converted by -C(O)N(H)Me, -OH, -NH2, -NH(C 1-4 alkyl), -N(C) 1-4 C-substituted with alkyl groups, -CO2Et, and -COOH 1-6 Alkyl; and R M6c Choose from the following groups: halogens, -NO2, -CN, C 2-4 Alkyne, 5-6 heteroaryl, and phenyl, wherein the 5-6 heteroaryl and phenyl groups are optionally selected from one or more halogens and C. 1-3 Alkyl group substitution; R M6d It is optionally selected by one or more halogens, -O(C 1-3 alkyl) and C 1-3 Alkyl groups substituted with 5- or 6-membered heteroaryl groups; and The wavy line represents the attachment point with L.

[0830] 220. A compound or its salt, solvate or prodrug according to any one of items 1 to 198, wherein M is , Where R M6b Is it H or ( S )-methyl, and the wavy line indicates the attachment point with L.

[0831] 221. A pharmaceutical composition comprising a compound according to any one of items 1 to 220 or a pharmaceutically acceptable salt, solvate or prodrug thereof, and one or more pharmaceutically acceptable excipients or carriers.

[0832] 222. A compound or salt thereof, solvate thereof, or prodrug, according to any one of items 1 to 220, or a pharmaceutical composition according to item 221, for use in a therapy.

[0833] 223. The compound or salt, solvate or prodrug thereof according to any one of items 1 to 220, or the pharmaceutical composition according to item 221, for use in the treatment or prevention of RIPK1-mediated diseases or conditions.

[0834] 224. The compound or its salt, solvate or prodrug, according to any one of items 1 to 220, or the pharmaceutical composition according to item 221, for use in the treatment or prevention of proliferative disorders, inflammatory diseases or conditions, neurodegenerative disorders or conditions, autoimmune disorders or conditions, or metabolic diseases or conditions.

[0835] 225. A compound or salt thereof, solvate thereof, or prodrug, according to any one of items 1 to 220, or a pharmaceutical composition according to item 221, for use in the treatment or prevention of cancer.

[0836] 226. The compound for use according to item 225, wherein the cancer is selected from the group consisting of: bladder cancer, leukemia, bone marrow cancer, brain cancer, breast cancer, bronchial cancer, colorectal cancer, cervical cancer, chondrosarcoma, endometrial cancer, gastrointestinal cancer, gastric cancer, genitourinary cancer, head and neck cancer, hepatic cancer, hepatocellular carcinoma, leukemia, liver cancer, lung cancer, lymphoma, melanoma of the skin, ovarian cancer, pancreatic cancer, prostate cancer, kidney cancer, skin cancer, testicular cancer, thyroid cancer, or uterine cancer.

[0837] While the invention may relate to any compound or particular group of compounds as defined herein in particular embodiments by way of optional, preferred or suitable features or otherwise, the invention may also relate to any compound or particular group of compounds that specifically excludes the optional, preferred or suitable features or particular embodiments.

[0838] Suitablely, the present invention excludes any individual compound that does not have the biological activity defined herein.

[0839] Salts and solvates The compounds described herein (including final products and intermediates) can be isolated and used on their own, or can be isolated in the form of salts, suitably pharmaceutically acceptable salts. It should be understood that, unless otherwise specified, the terms “salt” and “salt form” used alone or in combination with another or more terms cover all inorganic and organic salts, including industrially acceptable salts as defined herein and pharmaceutically acceptable salts as defined herein. As used herein, an industrially acceptable salt is one that is generally suitable for manufacture and / or processing (including purification) and for transport and storage, but may not be a salt that is generally administered for clinical or therapeutic use. Industrially acceptable salts can be prepared on a laboratory scale, i.e., in grams or less; or on a larger scale, i.e., up to and including kilograms or more.

[0840] As used herein, a pharmaceutically acceptable salt is a salt that is generally chemically and / or physically compatible with other ingredients comprising a formulation, and / or generally physiologically compatible with its recipient. Pharmaceutically acceptable salts can be prepared on a laboratory scale, i.e., in grams or less; or on a larger scale, i.e., up to and including kilograms or more. It should be understood that pharmaceutically acceptable salts are not limited to salts that are generally administered or approved by the FDA or an equivalent foreign regulatory agency for human clinical or therapeutic use. Those skilled in the art will readily understand that some salts are both industrially acceptable and pharmaceutically acceptable. It should be understood that all such salts, including mixed salt forms, are within the scope of this application.

[0841] In one embodiment, compounds of formula I and its sub-formulas are isolated into pharmaceutically acceptable salts.

[0842] Suitable pharmaceutically acceptable salts of the compounds of the present invention are, for example, acid addition salts of the compounds of the present invention that are sufficiently basic, such as acid addition salts with, for example, inorganic or organic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, trifluoroacetic acid, formic acid, citric acid, or maleic acid. Furthermore, suitable pharmaceutically acceptable salts of the compounds of the present invention that are sufficiently acidic are alkali metal salts such as sodium or potassium salts, alkaline earth metal salts such as calcium or magnesium salts, ammonium salts, or salts with organic bases that provide physiologically acceptable cations, such as salts with methylamine, dimethylamine, trimethylamine, piperidine, morpholine, or tri-(2-hydroxyethyl)amine.

[0843] Typically, the salts of this application can be prepared in situ during the separation and / or purification of compounds (including intermediates), or by reacting the compound (or intermediate) alone with a suitable organic or inorganic acid or organic or inorganic base (as the case may be) and separating the resulting salt. The degree of ionization of the salt can range from complete ionization to almost no ionization. In practice, multiple salts can be precipitated (with or without the addition of one or more co-solvents and / or antisolvents) and collected by filtration, or the salt can be recovered by evaporating the solvent. The salts of this application can also be formed via a “salt conversion” or ion exchange / double displacement reaction, i.e., a reaction in which one ion is replaced (entirely or partially) by another ion having the same charge. Those skilled in the art will understand that salts can be prepared and / or separated using a single method or a combination of methods.

[0844] Representative salts include, but are not limited to, acetates, aspartates, benzoates, benzenesulfonates, bicarbonates / carbonates, hydrogen sulfates / sulfates, borates, dextrorotatory camphor sulfonates, citrates, ethanedisulfonates, ethanesulfonates, formates, fumarates, glucohepanoates, glucuronates, glucuronates, hexafluorophosphates, phenacetinates, hydrochlorides / chlorides, hydrobromates / bromines, hydroiodates / iodides, hydroxyethyl sulfonates, lactates, malates, maleates, malonates, methanesulfonates, methyl sulfates, naphthates, 2-naphthalenesulfonates, nicotinates, nitrates, orotates, oxalates, palmitates, dihydroxynaphthalates, phosphates / hydrogen phosphates / dihydrogen phosphates, saccharates, stearates, succinates, tartrates, toluenesulfonates, trifluoroacetates, and similar salts. Other examples of representative salts include alkali metal cations or alkaline earth metal cations such as sodium, lithium, potassium, calcium, magnesium and the like, as well as non-toxic ammonium, quaternary ammonium and amine cations, including but not limited to ammonium, tetramethylammonium, tetraethylammonium, lysine, arginine, benzathine, choline, tromethamine, diethanolamine, glycine, meglumine, ethanolamine and the like.

[0845] Some compounds of Formula I and its subforms can exist in both solvated and non-solvated forms, such as, for example, hydrated forms. It should be understood that the present invention covers all such solvated forms having the biological activities described herein.

[0846] Polymorphs It should also be understood that certain compounds of Formula I and its subforms may exhibit polymorphism, and the present invention covers all such forms having the biological activities described herein.

[0847] N-oxides Compounds of formula I and its derivatives containing amine functionality can also form N-oxides. The compounds of formula I and its derivatives containing amine functionality mentioned herein also include N-oxides. In compounds containing several amine functions, one or more nitrogen atoms can be oxidized to form N-oxides. Specific examples of N-oxides are N-oxides of tertiary amines or nitrogen atoms in nitrogen-containing heterocycles. N-oxides can be formed by treating the corresponding amine with an oxidizing agent such as hydrogen peroxide or a peracid (e.g., peroxycarboxylic acid), see, for example, Jerry March's... Advanced Organic Chemistry , 4th edition, Wiley Interscience, page. More specifically, N-oxides can be obtained via LW Deady ( Syn. Comm The procedure described in 1977, 7, 509-514, involves the preparation of an amine compound with m-chloroperoxybenzoic acid (…). m CPBA) can be reacted, for example, in an inert solvent such as dichloromethane.

[0848] tautomer Compounds of Formula I and its subforms can...

Claims

1. A compound of formula I or a salt, solvate, or prodrug thereof: QLM (I) in Q is the formula Q 1 or Q 2 Protein-binding portion: (Q 1 ) (Q 2 ) in R 1 Choose the group consisting of the following items: C 3-11 cycloalkyl, C 3-11 cycloalkyl (C 1-3 )alkyl, 3- to 12-membered heterocyclic alkyl, 3- to 12-membered heterocyclic alkyl (C 1-3 )alkyl, 5- to 12-membered heteroaryl (C 1-6 )alkyl, C 1-10 Alkyl, C 2-10 alkenyl and C 2-10 Alkyne groups, wherein each is optionally surrounded by one or more R groups a1 replace; Each R a1 Choose independently the group consisting of: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 cycloalkyl, -OC 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=O)R b1 -C(=O)NR d1 R e1 -NR d1 R e1 -NR d1 C(=O)R b1 -OR c1 -SR c1 -OC(=O)R b1 -S(=O)2R c1 and -S(=O)2NR d1 R e1 Wherein C 1-6 Alkyl, OC 1-6 Alkyl, C 3-6 cycloalkyl, -OC 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl and C 6-11 The aryl group may optionally be substituted by one or more groups selected from the following: hydroxyl, halogen, =O, -CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl, phenyl, -C(O)C 1-6 Alkyl, -C(O)N(H)C 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl group 2, -CONH2, -C(O)N(H)C 1-6 Alkyl, -C(O)N(C) 1-6 Alkyl)2、-N(H)C 1-6 Alkyl and -N(C) 1-6 Alkyl)2; Where R b1 R c1 R d1 and R e1 Choose independently the group consisting of: hydrogen, hydroxyl, C 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 alkyl and phenyl, wherein the C 1-6 Alkyl, -OC 1-6 Alkyl, phenyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl; or R d1 and R e1 When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f1 replace; Each R f1 Choose independently the group consisting of the following items: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, phenyl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl; R 2 It is H, C 1-6 Alkyl, C 3-6 cycloalkyl or C 3-6 cycloalkyl-CH2-; B is selected from 5- to 12-membered heteroaryl groups or C 6-11 Aromatic cyclic groups; C is a heterocycle containing at least one nitrogen atom in the ring, and wherein -COOR 1 Part of it is bonded to the ring C via nitrogen atoms in the ring C; A is a cyclic group selected from 5-membered to 15-membered heteroaryl groups; V is selected from the following groups: -NH-, -C(O)N(H)-, -N(H)C(O)-, -S(O)(NH)-, -N(H)S(O)-, -S(O)N(H)-, -N(H)S(O)2- and -S(O)2N(H)-; R 3 and R 9 Choose independently the group consisting of: hydroxyl, =O, halogen, CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, -C(=O)R b3 -C(=O)OR c3 -C(=O)NR d3 R e3 -NR d3 R e3 -NR d3 C(=O)R b3 -OR c3 -SR c3 Wherein C 1-6 Alkyl, OC 1-6 Alkyl, C 3-6 Cycloalkyl, 3-7-membered heterocycloalkyl, 5-6-membered heteroaryl, and phenyl groups are optionally substituted by one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, OC 1-6 Alkyl, -NH2, -N(H)C 1-3 Alkyl and -N(C) 1-3 Alkyl)2; Where R b3 R c3 R d3 and R e3 Choose independently the group consisting of: hydrogen, hydroxyl, C 1-6 Halogenated alkyl, OC 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl and C 6-15 Aryl, wherein the C 1-6 Alkyl, -OC 1-6 Alkyl, C 6-15 Aryl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl; or R d3 and R e3 When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f3 replace; Each R f3 Choose independently the group consisting of the following items: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl; R 4 Choose from the group consisting of: hydroxyl, =O, halogen, -CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 1-6 Alkyl, -OC 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, C 6-11 Aryl, 5-11 heteroaryl, -C(=O)R b4 -C(=O)OR c4 -C(=O)NR d4 R e4 -NR d4 R e4 -NR d4 C(=O)R b4 -NR d4 C(=O)OR c4 -NR d4 C(=O)NR d4 R e4 -NR d4 S(=O)2R b4 -NR d4 S(=O)2NR d4 R e4 -OR c4 -SR c4 -OC(=O)R b4 -OC(=O)NR d4 R e4 -OC(=O)OR c4 -S(=O)2R c4 -S(=O)R c4 -OS(=O)R c4 -OS(=O)2R c4 -OS(=O)2OR c4 -S(=O)NR d4 R e4 -OS(=O)2NR d4 R e4 and -S(=O)2NR d4 R e4 Wherein C 1-6 Alkyl, -OC 1-6 Alkyl, C 3-6 Cycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl and C 6-11 The aryl group may optionally be substituted by one or more groups selected from the following: hydroxyl, halogen, =O, CN, C. 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl, phenyl, -NH2, -NHR' and -NR'R'', wherein R' and R'' are independently selected from C 1-6 Alkyl group, wherein the phenyl group is optionally hydroxyl, halogen, =O, -CN, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy groups, C 3-6 cycloalkyl, C 1-6 Alkyl and -OC 1-6 One or more alkyl groups are substituted; Where R b4 R c4 R d4 and R e4 Choose independently the group consisting of: hydrogen, hydroxyl, C 1-6 Halogenated alkyl groups, -OC 1-6 Haloalkyl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl, C 1-6 Alkyl, -OC 1-6 Alkyl and C 6-15 Aryl, wherein the C 1-6 Alkyl, C 6-15 Aryl, 3-7 membered heterocyclic alkyl, 5-6 membered heteroaryl and C 3-6 The cycloalkyl group is optionally substituted with one or more groups selected from the following: hydroxyl, halogen, -CN, -NO2, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 Alkyl; or R d4 and R e4 When attached to the same atom, they form 3-7 membered rings together with the atoms to which they are attached, the 3-7 membered rings optionally containing one or more heteroatoms selected from O, N, and S, and wherein the rings are optionally separated by one or more R atoms. f4 replace; Each R f4 Choose independently the group consisting of the following items: hydrogen, =O, halogen, -CN, -NH2, -N(H)C 1-6 Alkyl, -N(C) 1-6 Alkyl)2, C 1-6 Haloalkyl, C 3-6 cycloalkyl, C 6-11 Aryl, 3-7 membered heterocyclic alkyl, C 1-6 Alkyl and -OC 1-6 alkyl; y1, y2, z1, and z2 are integers independently selected from 0, 1, 2, 3, and 4; L is the connector part; and M is the E3 ubiquitin ligase binding site.

2. The compound or its salt, solvate or prodrug according to claim 1, wherein A is a cyclic group of formula A1. (A1)， Where X 1 X 2 X 3 and X 4 Independently selected from C, N, CH or CR 4 The condition is X 1 X 2 X 3 and X 4 Only one of them is C and forms an attachment point with ring B; X 5 and X 6 Independently selected from N or C; X 7 and X 8 Independently selected from O, S, N, CH, CR 4 and NR 4 ; The condition is X 1 X 2 X 3 X 4 X 5 X 6 X 7 and X 8 At least one of them must be N.

3. The compound or its salt, solvate or prodrug according to claim 1 or claim 2, wherein A is a group selected from the following: 。 4. The compound or its salt, solvate or prodrug according to any one of the preceding claims, wherein R 1 Choose the group consisting of the following items: C 3-7 Cycloalkyl, 3- to 7-membered heterocycloalkyl and C 1-6 Alkyl groups, wherein each is optionally surrounded by one or more R groups a1 replace.

5. The compound, salt, solvate, or prodrug of any one of the preceding claims, wherein R 1 Selected from the following groups, each optionally bound by one or more R groups a1 replace: 。 6. The compound or its salt, solvate or prodrug according to any one of the preceding claims, wherein V is selected from -N(H)-, C(O)N(H)- or -N(H)C(O)-.

7. The compound or its salt, solvate or prodrug according to any one of the preceding claims, wherein B has the formula B1: (B1)， Where X 9 and X 10 Independently selected from N and CR 3 Or CH.

8. The compound or its salt, solvate or prodrug according to any one of the preceding claims, wherein B has the formula B2: (B2)。 9. The compound, salt, solvate, or prodrug of any of the preceding claims, wherein Q has the formula Q 1b : (Q 1b ) Where R 2a It is hydrogen or methyl, preferably hydrogen; or Where Q has a subform Q 1c : (Q 1c ) Where R 2a It is hydrogen or methyl, preferably hydrogen; X 3 It is as defined in claim 2, and X 10 It is as defined in claim 7; or Where Q has a subform Q 1d : (Q 1d ) Where R 2a It is hydrogen or methyl, preferably hydrogen; X 1 As defined in claim 2, X 9 and X 10 It is as defined in claim 7, and X 7a It is CH or N.

10. The compound or its salt, solvate or prodrug according to any one of claims 1 to 6, wherein C has the formula C1: (C1) in Dashed line indicates -COOR 1 Attachment point; X 12 X 13 and X 14 Independently selected from N and CR 9 Or CH; X 15 It is CH2, CHR 9 C(R) 9 2. NH, NR 9 S, S(O), S(O)2 or O; and n C It is an integer selected from 0, 1, or 2.

11. The compound or its salt, solvate or prodrug according to any one of claims 1 to 6 and 10, wherein C is selected from: Each of them can be arbitrarily assigned to R 9 replace.

12. The compound or its salt, solvate or prodrug according to any one of claims 1 to 6, 10 and 11, wherein Q has the formula Q 2c Q 2d Q 2e Or Q 2f : (Q 2c )； (Q 2d )； (Q 2e )； (Q 2f )； Where R 1 As defined in claim 1, X 15 Selected from CH2, CHR 9 C(R) 9 2. NH, NR 9 S, S(O), S(O)2 or O, X 1 It is as defined in claim 2, and X 7b It is CH or N.

13. The compound or its salt, solvate or prodrug according to any one of the preceding claims, wherein L is selected from: (L3), where n4 is an integer value from 0 to 20; (L4), where n4a is an integer value from 0 to 20; (L5), where n3 is a value from 1 to 10, and each n5 is an independent integer value from 0 to 5; (L6)， Where n3 is a value from 1 to 10, and each n5 is an independent integer value from 0 to 5; (L7)， Where n12 is a value from 2 to 10; (L8)， Where n6 is an integer value from 0 to 10, n7 is a value from 1 to 12; n19 is an integer value of 0 or 1; and the ring D is optionally bounded by one or more R... 7 Substituted phenyl or 6-membered heteroaryl ring; and wherein R 7 Choose from the following groups: hydrogen, hydroxyl, =O, C 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl groups, phenyl groups, 5-6-membered heteroaryl groups, 3- to 7-membered heterocyclic alkyl groups, and C 3-6 Cycloalkyl groups, each of which can optionally be composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; (L9)， Where n8 is a value from 1 to 12; (L10)， Where n11 is an integer value from 0 to 12, and the ring E is optionally bounded by one or more R... 7 Substituted phenyl or 6-membered heteroaryl ring; (L11)， Each of n12 and n13 is an independent integer value from 0 to 5, and the ring F is optionally bounded by one or more R... 7 Substituted 5- or 6-membered heterocyclic alkyl rings; or (L11a); Where ring K1 can be arbitrarily divided by one or more R... 24 Substituted 5- to 10-membered heterocyclic alkyl rings; n40 is an integer value from 0 to 8; n41 is an integer value from 0 to 8; R 24 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl and C 3-6 Cycloalkyl groups, each of which can optionally be composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; or (L11b); Where ring K2 can be arbitrarily divided by one or more R... 25 Substituted 5- to 10-membered heterocyclic alkyl rings; n42 is an integer value from 0 to 8; n43 is an integer value from 0 to 8; n44 and n45 are independently selected from integer values ​​0 to 5; and R 25 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl and C 3-6 Cycloalkyl groups, each of which can optionally be composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; or (L11c); Where ring K3 can be arbitrarily divided by one or more R... 27 Substituted 4- to 10-membered heterocyclic alkyl rings; n47 is an integer value from 0 to 3; n48 is selected from integer values ​​0 to 5; n49 is an integer value of 0 or 1; R 12 and R 13 Independently selected from H, halogen, C 1-4 Alkyl, C 3-6 cycloalkyl; or R 12 and R 13 Together with the carbon atoms to which they are attached, they form C 3-6 cycloalkyl groups; and R 27 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl and C 3-6 Cycloalkyl groups, each of which can optionally be composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; or (L12)； Each n14 and n15 is independently an integer value from 0 to 5, and rings G and H are independently selected from the group consisting of: 5- to 7-membered heterocyclic alkyl groups, 5- or 6-membered heteroaryl groups, and C3-C4 groups. 10 Cycloalkyl groups, each of which can optionally be converted by one or more R groups. 7 replace; (L13)； Where n16 is an integer value of 0 or 1, and n17 is a value from 1 to 12; and (L14a); Where n18 is a number from 1 to 5, and rings G1 and H1 are independently selected from the group consisting of: 5- to 7-membered heterocyclic alkyl groups, 5- or 6-membered heteroaryl groups, and C3-C4 groups. 10 Cycloalkyl groups, each of which can optionally be converted by one or more R groups. 7 Replace; or (L14b); Where n20 is a value from 1 to 5; Where n21 and n27 are independent integer values ​​0 or 1; The rings G2 and H2 are independently selected from the group consisting of: 5- to 10-membered heterocyclic alkyl groups, 5- or 6-membered heteroaryl groups, and C3-C. 10 Cycloalkyl groups, each of which can optionally be converted by one or more R groups. 8 replace; R 8 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl and C 3-6 Cycloalkyl groups, each of which can optionally be composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; and R 10 and R 11 Independently selected from H and C 1-4 Alkyl, C 3-6 cycloalkyl; or R 10 and R 11 Together with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups; or (L14c); Where n23 is an integer value of 0 or 1; n24 is an integer value from 0 to 3; The rings G3 and H3 are independently selected from the group consisting of: 4- to 10-membered heterocyclic alkyl groups, 5- or 6-membered heteroaryl groups, and C3-C. 10 Cycloalkyl groups, each of which can optionally be converted by one or more R groups. 8c replace; R 8c Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl and C 3-6 Cycloalkyl groups, each of which can optionally be composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; and R 12c and R 13c Independently selected from H, halogen, C 1-4 Alkyl, C 3-6 cycloalkyl; or R 12c and R 13c Together with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups; or (L14d); Where n26 is an integer value of 0 or 1; n28 is an integer value of 0, 1, or 2; Z does not exist or is selected from NH, N(C) 1-3 Alkyl), O, or S groups; The rings G4 and H4 are independently selected from the group consisting of: 4- to 10-membered heterocyclic alkyl groups, 5- or 6-membered heteroaryl groups, and C3-C. 10 Cycloalkyl groups, each of which can optionally be converted by one or more R groups. 8d replace; R 8d Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl and C 3-6 Cycloalkyl groups, each of which can optionally be composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; R 10d and R 11d Independently selected from H and C 1-4 Alkyl, C 3-6 cycloalkyl; or R 10d and R 11d Together with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups; R 12d and R 13d Independently selected from H, halogen, C 1-4 Alkyl, C 3-6 cycloalkyl; or R 12d and R 13d Together with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups; or (L14e); Where n50 and n51 are independent integer values ​​0 or 1; n52 and n53 are independent integer values ​​of 0, 1 or 2; The rings G5, H5, and D5 are independently selected from the group consisting of: 4- to 10-membered heterocyclic alkyl groups, 5- or 6-membered heteroaryl groups, and C3-C. 10 Cycloalkyl groups, each of which can optionally be converted by one or more R groups. 8e replace; R 8e Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl and C 3-6 Cycloalkyl groups, each of which can optionally be composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; and R 10e and R 11e Independently selected from H and C 1-4 Alkyl, C 3-6 cycloalkyl; or R 10e and R 11e Together with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups; R 12e and R 13e Independently selected from H, halogen, C 1-4 Alkyl, C 3-6 cycloalkyl; or R 12e and R 13e Together with the carbon atoms to which they are attached, they form C 3-6 Cycloalkyl groups; or (L15)， Wherein ring D1 is a 5- or 6-membered heteroaryl ring or a phenyl ring, each of which can optionally be separated by one or more R groups. 20 replace; n30 is an integer value from 0 to 5; n31 is a value from 1 to 12; and n32 is an integer value of 0 or 1; and R 20 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl and C 3-6 Cycloalkyl groups, each of which can optionally be composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; or (L16)； Where ring J is arbitrarily construed by one or more Rs 23 Substituted 5- to 10-membered heterocyclic alkyl rings; n33 is an integer value from 0 to 5; n34 is a value from 1 to 12; and n35 is an integer value of 0 or 1; and R 23 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl and C 3-6 Cycloalkyl groups, each of which can optionally be composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; (L16a); Where ring J1 can be arbitrarily divided by one or more Rs 26 Substituted 4- to 10-membered heterocyclic alkyl rings; Z 1 It does not exist or is selected from NH, N(C) 1-3 Alkyl), O, or S groups; n37 and n38 are independently selected from integer values ​​0 to 5; and n36 and n39 are independently selected from integer values ​​0 or 1; and R 26 Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl and C 3-6 Cycloalkyl groups, each of which can optionally be composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups; or (L16b); Where ring J2 can be arbitrarily divided by one or more R 26b Substituted 4- to 10-membered heterocyclic alkyl rings; Z 2 It does not exist or is selected from NH, N(C) 1-3 Alkyl), O, or S groups; n57 and n58 are independently selected from integer values ​​0 to 5; and n56 and n59 are independently selected from integer values ​​0 or 1; and R 26b Each time it appears, independently select the group consisting of the following items: hydroxyl, =O, C. 1-4 Alkyl, C 1-4 alkenyl, C 2-4 alkynyl group, C 1-4 Halogenated alkyl and C 3-6 Cycloalkyl groups, each of which can optionally be composed of one or more molecules selected from C10 and C20. 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Substitution of cycloalkyl, phenyl, and hydroxyl groups.

14. The compound or its salt, solvate or prodrug according to any one of the preceding claims, wherein L is a connector according to one of formula L3, L4, L5, L11, L11b, L11c, L13, L14a, L14b, L14c, L14d, L14e, L15, L16, L16a.

15. The compound or its salt, solvate or prodrug according to any one of the preceding claims, wherein L is a connector according to one of formula L3, L4, L11b, L11c, L13, L14b, L14c, L14d, L15, L16, L16a.

16. The compound or its salt, solvate or prodrug according to any one of the preceding claims, wherein M is an E3 ubiquitin ligase binding moiety capable of binding to VHL.

17. The compound or its salt, solvate or prodrug according to any one of the preceding claims, wherein M is the E3 ubiquitin ligase-binding moiety of formula M1, M2, M3 or M6: (M1)； in R M1a It can be selectively converted by halogens, -OH, -O(C) 1-4 alkyl), -S(C 1-4 alkyl) substituted C 2-6 alkyl groups; R M1b Selected from hydrogen or optionally by -C(O)N(H)Me, -OH, -NH2, -NH(C 1-4 alkyl), -N(C) 1-4 C-substituted with alkyl groups, -CO2Et, and -COOH 1-6 Alkyl; and R M1c Choose from the following groups: halogens, -NO2, -CN, C 2-4 Alkyne, 5-6 heteroaryl, and phenyl, wherein the 5-6 heteroaryl and phenyl groups are optionally selected from one or more halogens and C. 1-3 Alkyl group substitution; (M2)； in R M2a It can be selectively converted by halogens, -OH, -O(C) 1-4 alkyl), -S(C 1-4 alkyl) substituted C 2-6 alkyl groups; R M2d Selected from: R M2b Selected from hydrogen or optionally by -C(O)N(H)Me, -OH, -NH2, -NH(C 1-4 alkyl), -N(C) 1-4 C-substituted with alkyl groups, -CO2Et, and -COOH 1-6 Alkyl; and R M2c Choose from the following groups: halogens, -NO2, -CN, C 2-4 Alkyne, 5-6 heteroaryl, and phenyl, wherein the 5-6 heteroaryl and phenyl groups are optionally selected from one or more halogens and C. 1-3 Alkyl group substitution; (M3)； R M3a It can be selectively converted by halogens, -OH, -O(C) 1-4 alkyl), -S(C 1-4 alkyl) substituted C 2-6 alkyl groups; R M3d Selected from: ;and R M3c Choose from the following groups: halogens, -NO2, -CN, C 2-4 Alkyne, 5-6 heteroaryl, and phenyl, wherein the 5-6 heteroaryl and phenyl groups are optionally selected from one or more halogens and C. 1-3 Alkyl group substitution; (M6)； in R M6a It can be selectively converted by halogens, -OH, -O(C) 1-4 alkyl), -S(C 1-4 alkyl) substituted C 2-6 alkyl groups; R M6b Selected from hydrogen or optionally by -C(O)N(H)Me, -OH, -NH2, -NH(C 1-4 alkyl), -N(C) 1-4 C-substituted with alkyl groups, -CO2Et, and -COOH 1-6 Alkyl; and R M6c Choose from the following groups: halogens, -NO2, -CN, C 2-4 Alkyne, 5-6 heteroaryl, and phenyl, wherein the 5-6 heteroaryl and phenyl groups are optionally selected from one or more halogens and C. 1-3 Alkyl group substitution; R M6d It is optionally selected by one or more halogens, -O(C 1-3 alkyl) and C 1-3 Alkyl groups substituted with 5- or 6-membered heteroaryl groups.

18. The compound or its salt, solvate or prodrug according to any one of the preceding claims, wherein M is an E3 ubiquitin ligase-binding moiety selected from: (i) , where R M1b Is it H or ( S )-methyl; (ii) , where R M2e It is either F or CN; (iii) ； (vi) ； (vii) , where R M6b Is it H or ( S )-methyl; The wavy key represents the attachment point with L.

19. A compound or its salt, solvate or prodrug, selected from: 。 20. A pharmaceutical composition comprising a compound according to any one of claims 1 to 19 or a pharmaceutically acceptable salt, solvate or prodrug thereof, and one or more pharmaceutically acceptable excipients or carriers.

21. The compound of any one of claims 1 to 19, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or the pharmaceutical composition of claim 20, for use in a therapy.

22. The compound of any one of claims 1 to 19, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or the pharmaceutical composition of claim 20, for use in the treatment or prevention of RIPK1-mediated diseases or conditions.

23. The compound of any one of claims 1 to 19, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or the pharmaceutical composition of claim 20, for use in the treatment or prevention of proliferative disorders, inflammatory diseases or conditions, neurodegenerative disorders or conditions, autoimmune disorders or conditions, or metabolic diseases or conditions.

24. The compound of any one of claims 1 to 19, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or the pharmaceutical composition of claim 20, for use in the treatment or prevention of cancer.

25. A salt, solvate, or prodrug of the compound for use or a pharmaceutically acceptable compound thereof according to claim 24, wherein the cancer is selected from the group consisting of: bladder cancer, leukemia, bone marrow cancer, brain cancer, breast cancer, bronchial cancer, colorectal cancer, cervical cancer, chondrosarcoma, endometrial cancer, gastrointestinal cancer, gastric cancer, genitourinary cancer, head and neck cancer, liver cancer, hepatocellular carcinoma, leukemia, liver cancer, lung cancer, lymphoma, melanoma of the skin, ovarian cancer, pancreatic cancer, prostate cancer, kidney cancer, skin cancer, testicular cancer, thyroid cancer, and uterine cancer.

26. The compound for use according to claim 24 or claim 25, wherein the compound is used in combination with one or more other therapeutic agents or treatments such as antitumor agents and / or radiotherapy.

27. A combination comprising a compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, and an additional therapeutic agent.

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