Compounds for inhibiting or degrading CDK2 and / or CDK9 and their pharmaceutical applications

Abstract

The present invention provides compounds of a specific chemical structure or pharmaceutically acceptable salts thereof that have the activity of inhibiting or degrading CDK2 and / or CDK9, as well as methods for producing the same. The present invention also provides compositions containing such compounds or pharmaceutically acceptable salts thereof. The present invention also provides pharmaceutical uses of the compounds according to the present invention, salts thereof, and compositions containing them for inhibiting or degrading CDK2 and / or CDK9, as well as for preventing or treating diseases associated therewith. The present invention also provides methods for preventing or treating CDK2- and / or CDK9-related diseases, comprising administering an effective amount of a compound according to the present invention, a salt thereof, or a composition containing them to an individual in need of treatment.

Description

[Technical Field]

[0001] The present invention relates to a group of compounds having activity to inhibit or degrade CDK2 (cyclin-dependent kinase 2) and / or CDK9 (cyclin-dependent kinase 9), and to methods for producing these compounds. The present invention also relates to pharmaceutical compositions comprising such compounds. The present invention also relates to useful methods for treating CDK2 or CDK9-related diseases using such compounds. 、 The present invention relates to pharmaceutical uses of the compounds according to the present invention for treating or preventing CDK2 or CDK9-related diseases. [Background technology]

[0002] CDKs (cyclin-dependent kinases) are serine / threonine protein kinases that are activated through binding to cyclin. While CDKs have several isoforms, humans express 21 different CDK isoforms. Each CDK plays a distinct role within the cell, but functionally, they can be broadly divided into those involved in cell cycles and those involved in transcription.

[0003] CDK2 is one of the CDKs that regulate the cell cycle, and it is activated through binding to cyclin E or cyclin A. The CDK2-cyclin E complex regulates the transition to the S-phase, while the CDK2-cyclin A complex plays a role in regulating DNA synthesis in the S-phase. Unregulated CDK2 activation induces cells to enter the S-phase even in the absence of growth factors, which increases chromosomal instability and cell proliferation, leading to cancer. In fact, it has been reported that CDK2 (prostate cancer, B cell lymphoma, glioblastoma; Cell Cycle, 2007, 6:2982-2989, Future Oncol., 2018, 14:709-718, Transl. Oncol., 2016, 9:548-556) and cyclin E1 (ovarian cancer, TNBC, hepatocellular carcinoma; Oncotarget, 2015, 6:20801-20812, Clin. Cancer Res., 2017, 23:1862-1874, Oncol. Rep., 2015, 33:990-996, Gynecol. Oncol., 2018, 151:327-336, Oncotarget, 2017, 8:14897-14911) are overexpressed in a variety of cancers. These research findings suggest that therapeutic effects can be expected in cancers overexpressing CDK2 through the selective degradation of CDK2. Furthermore, International Patent Publication WO 2006 / 040036 discloses that CDK2 inhibitors are useful in the treatment of breast cancer, colorectal cancer, lung cancer, and prostate cancer.

[0004] CDK9 is one of the CDKs that regulate transcription. CDK9 binds to cyclin T1, cyclin T2, or cyclin K to form the P-TEFb (positive transcription elongation factor) complex. The P-TEFb complex phosphorylates RNA polymerase II, thereby promoting transcription elongation. CDK9 regulates the expression of the transcription factor Myc (Mol. Cancer Ther., 2019, 18:1520-32) and the anti-apoptotic protein MCL-1 (Am. J. Manag. Care, 2018, 24:S356-S365) in cancer. Therefore, suppression of CDK9 inhibits the proliferation of various cancer cells (prostate, pancreatic, breast, multiple myeloma), including chronic lymphocytic leukemia (CLL) (Endocrine-Related Cancer, 2016, 23, T211-T226). In addition, since human immunodeficiency virus (HIV) utilizes the host's P-TEFb for viral replication, CDK9 is used as a candidate target protein to suppress HIV replication (Cancer Biol. Ther., 2002, 1:342-347). Furthermore, International Patent Publication WO 2017 / 001354 discloses that CDK9 inhibitors are useful in treating cancers such as acute myeloid leukemia, multiple myeloma, chronic lymphocytic leukemia, diffuse large B-cell lymphoma, Burkitt lymphoma, follicular lymphoma, breast cancer, lung cancer, neuroblastoma, and colon cancer, and also discloses that they have therapeutic utility in other disease indications, including heart disease, viral diseases, inflammation, and pain.

[0005] Meanwhile, in recent years, Proteolysis Targeting Chimera (PROTAC) technology, which degrades target proteins, has been actively utilized in new drug development (PNAS, 2001, 98(15):8554-8559, Cell, 2020, 2:1-3). PROTACs are novel therapeutic agents manufactured by linking inhibitor or binder compounds that bind to specific proteins with ligand compounds that bind characteristically to E3 ubiquitin ligases using various types of linkers. Because PROTAC substances target and degrade only the target proteins that cause disease, the possibility of developing drug resistance is low, and sufficient therapeutic effects can be achieved through the degradation of target proteins even without high binding affinity to the target protein. Furthermore, they can be applied to targets that were undruggable targets that could not be treated with existing drugs, and are attracting attention as a novel therapeutic technology.

[0006] However, simply binding an E3 ubiquitin ligase ligand compound to all inhibitors (binding factors) does not necessarily result in an effective PROTAC substance; its effect varies depending on the binding molecule, such as the inhibitor, E3 ubiquitin ligase ligand, or linker. [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] International Patent Publication WO 2006 / 040036 [Patent Document 2] International Patent Publication WO 2017 / 001354 [Patent Document 3] US20180353501 A1 [Patent Document 4] WO2019199816A1 [Patent Document 5] WO2019023553 A1 [Patent Document 6] US20180125821 A1 [Patent Document 7] US20190192668 A1 [License 8] WO2017197056 A1 [License 9] WO2019186358 A1 [License 10] WO2018089736 A1 [License 11] Korean Registration License No. 1893879 [Non-licensed literature]

[0008] [Non-licensed Document 1] prostate cancer, B cell lymphoma, glioblastoma; Cell Cycle, 2007, 6: 2982-2989, Future Oncol., 2018, 14: 709-718, Transl. Oncol., 2016, 9: 548-556 [Non-licensed Document 2] ovarian cancer,TNBC,hepatocellular carcinoma;Oncotarget, 2015,6:20801-20812,Clin.Cancer Res., 2017,23:1862-1874,Oncol.Rep., 2015,33:990-996,Gynecol.Oncol., 2018,151:327-336,Oncotarget, 2017,8:14897-14911 [Non-licensed Document 3] Mol.Cancer Ther., 2019,18:1520-32 [Non-licensed Document 4] Am.J.Manag.Care、2018,24:S356-S365 [Non-licensed Document 5] Endocrine-Related Cancer、2016,23,T211-T226 [Non-licensed Document 6] Cancer Biol. Ther., 2002,1:342-347 [Non-licensed Document 7] PNAS, 2001,98(15):8554-8559,Cell, 2020,2:1-3 [Overview of the project] [Problems that the invention aims to solve]

[0009] One object of the present invention is to provide a compound having inhibitory and / or degradative activity of CDK2 and / or CDK9, or a pharmaceutically acceptable salt thereof.

[0010] Another object of the present invention is to provide a method for producing the compound or a pharmaceutically acceptable salt thereof.

[0011] Another object of the present invention is to provide a composition comprising the compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0012] Another object of the present invention is to provide a pharmaceutical composition for inhibiting or degrading CDK2, CDK9, or both, comprising the compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0013] Another object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of cancer or human immunodeficiency virus (HIV) infection, comprising the compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0014] Another object of the present invention is to provide a method for preventing or treating cancer or human immunodeficiency virus infection, comprising the step of administering the pharmaceutical composition to an individual in need thereof. [Effects of the Invention]

[0015] The present invention provides compounds or pharmaceutically acceptable salts thereof that inhibit or degrade CDK2 and / or CDK9 and exhibit diverse pharmacological activities, pharmaceutical compositions containing these as active ingredients, pharmaceutical uses thereof (particularly for the treatment or prevention of cancer or human immunodeficiency virus (HIV) infection), and therapeutic methods comprising administering these to individuals in need of treatment or prevention. The compounds or pharmaceutically acceptable salts thereof according to the present invention are excellent in various aspects such as safety and stability, and exhibit high selectivity in terms of inhibiting or degrading CDK2 and / or CDK9 activity, thus demonstrating excellent pharmaceutical effects. [Brief explanation of the drawing]

[0016] [Figure 1] This figure illustrates the results of evaluating the CDK protein degradation activity of some compounds according to the present invention. [Figure 2] This figure illustrates the results of the evaluation of the cytotoxicity of some compounds according to the present invention. [Figure 3-13] This figure summarizes the results of analyzing 479 compounds synthesized according to the present invention using a mass spectrometer and / or NMR spectrometer. [Modes for carrying out the invention]

[0017] Each description and embodiment disclosed in this invention also applies to each other description and embodiment. 、 Any combination of the various elements disclosed in this application falls within the scope of the present invention. Furthermore, the scope of the present invention is not considered to be limited by the following specific descriptions.

[0018] Furthermore, a person with ordinary skill in the art can recognize or confirm numerous equivalents to the specific modes of the present invention described herein using only ordinary experiments. Such equivalents are intended to be included in the present invention.

[0019] Furthermore, throughout the specification of the present invention, when a part is said to "comprise" a certain component, this does not exclude other components unless otherwise specifically stated, and means that other components may be further included. The following description is merely exemplary and is not intended to limit the present invention, the application, or the use thereof.

[0020] Hereinafter, the present invention will be described in more detail.

[0021] To achieve the above object, a first aspect of the present invention provides a compound represented by the following Chemical Formula 1, or a pharmaceutically acceptable salt thereof:

[0022]

Chemical Formula

[0023] In the Chemical Formula 1, R1 is C 1-10 alkyl, aryl, -C 1-3 alkyl-C 6-10 aryl, 5-10 membered heteroaryl, -C 1-3 alkyl-5-10 membered heteroaryl, C 3-10 cycloalkyl, -C 1-3 alkyl-C 3-10 cycloalkyl, 3-10 membered heterocycloalkyl, or -C 1-3 alkyl-3-10 membered heterocycloalkyl, wherein the aryl, heteroaryl, cycloalkyl, or heterocycloalkyl is unsubstituted, or substituted with halogen, cyano, tert-butoxycarbonyl (-Boc), amino, nitro, hydroxy, C 1-6 alkyl, halo-C 1-6 alkyl, -OR a , -C(=O)R a , -C(=O)OR a , -C(O)NR a R b , -SO2R a , -S(O)R a , -SO(N)R a , C 1-2 alkyl-C6-10 Aryl and C 6-10 It is replaced by one or more selected from the group composed of aryls, where R a and R b They are the same or different, and independently of each other, hydrogen, halogen, amino, and C 1-6 Alkyl, Halo-C 1-6 Alkyl, C 6-10 Aryl, 5-10 membered heteroaryl, C 3-10 It is a cycloalkyl or 3-10 member heterocycloalkyl, A is a moiety that acts as an exit vector. L stands for linker. ELB is an E3 ubiquitin ligase binder.

[0024] For example, in the above chemical formula 1, ELB may have the structure of the following chemical formula 2:

[0025] [ka]

[0026] In the aforementioned chemical formula 2, Cy is C 6-10 Aryl, 5-10 membered heteroaryl, or 5-10 membered heterocycloalkyl; k is between 0 and 2; X is either N or C; R2 is absent, hydrogen, deuterium (D), or C1-C3 alkyl; The aryl, heteroaryl, or heterocycloalkyl elements may be unsubstituted, or oxo, halogen, nitro, amino, hydroxy, carboxy, or C. 1-6 Alkyl, or C 1-6 It is replaced by one or more elements selected from the group composed of alkoxys.

[0027] in particular 、 The aforementioned chemical formula 2 may be any of the following structures, but is not limited thereto:

[0028] [ka]

[0029] (R3 is hydrogen or halogen, and X2 is CH or N).

[0030] More specifically 、 The aforementioned chemical formula 2 may be any of the following structures, but is not limited thereto:

[0031] [ka] .

[0032] For example, in the above chemical formula 1, R1 is C 1-6 Alkyl, -C 1-3 Alkyl-phenyl, phenyl, -C 1-3 Alkylpyridyl, or pyridyl, where phenyl or pyridyl may be unsubstituted or C 1-3 Alkyl, halogen, cyano, and halo-C 1-3 The molecule may be substituted with one or more substituents selected from the group consisting of alkyl groups, but is not limited thereto.

[0033] in particular 、 The aforementioned R1 may be any of the following structures, but is not limited thereto:

[0034] [ka]

[0035] For example, in the above chemical formula 1, A may have the structure of the following chemical formula 3, but is not limited thereto:

[0036] [ka]

[0037] In the aforementioned chemical formula 3, Cy1 is either unsubstituted or C 1-3 C substituted with alkyl 6-10 Aryl or 5-10 membered heteroaryl, Cy2 is a 3-10 member heterocycloalkyl group. l is an integer between 0 and 4, and m, n, and p are independently 0 or 1, except when all are 0.

[0038] in particular 、 The aforementioned A may be any of the following structures, but is not limited thereto:

[0039] [ka]

[0040] For example, in the above chemical formula 1, the linker can be represented as -L1-L2-.

[0041] At that time, L2 was directly connected.

[0042] [ka]

[0043] Therefore, L1 is,

[0044] [ka]

[0045] or

[0046] [ka]

[0047] That's fine.

[0048] Here, q, t, v, and y are independently 0 or 1, r, s, u, and x are independently integers from 0 to 6, and Cy3 and Cy4 are independently non-existent 3-10 membered heterocycloalkyl or C 3-10 It may be a cycloalkyl group, but is not limited to that.

[0049] in particular 、 The aforementioned L1 may be any of the following structures, but is not limited thereto:

[0050] [ka]

[0051] In one embodiment of the present invention, the ELB moisture of chemical formula 1 represents an E3 ligase ligand, and the CDK2 and / or CDK9 binder moisture of chemical formula 1 according to the present invention plays a role in linking the target protein, which is CDK2 and / or CDK9, to the E3 ligase after binding to CDK2 and / or CDK9 (step 1). After ubiquitination of the lysine of the target protein by E2, which is complexed with the E3 ligase, occurs (step 2), and then the CDK2 and / or CDK9 are degraded or inhibited through a process by which they are degraded by the proteasome (step 3). Such a degrader can be recycled in a similar manner (step 4).

[0052] In one embodiment of the present invention, the linker of chemical formula 1 is a linker that links a CDK2 and / or CDK9 inhibitor to an E3 ligase ligand compound, and such a linker can be linked to the CDK2 and / or CDK9 inhibitor compound via an alkyl bond through a chloride, bromide, iodide, or tosylate, or via an amide bond through an acid or an amide bond through an amine. For example, linkers disclosed in prior patents US20180353501 A1, WO2019199816 A1, WO2019023553 A1, US20180125821 A1, US20190192668 A1, WO2017197056 A1, WO2019186358 A1, and / or WO2018089736 A1 may be used as such linkers. The contents described in the aforementioned prior patent application publication are incorporated in their entirety by this reference.

[0053] In a typical embodiment, the linker has a chain of 2 to 14, 15, 16, 17, 18, or 20 or more carbon atoms, one or more of which carbon atoms may be replaced by heteroatoms such as O, N, S, or P. In certain specific examples, the chain has 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 adjacent atoms. For example, the chain may contain one or more ethylene glycol units that are continuous, partially continuous, or discontinuous (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 ethylene glycol units). In certain specific examples, the chain has at least 1, 2, 3, 4, 5, 6, 7, or 8 continuous chains, each having branches that are independently alkyl, heteroalkyl, aryl, heteroaryl, alkenyl, or alkynyl, cycloalkyl, or heterocycloalkyl substituted.

[0054] In other specific examples, the linker may contain or be composed of one or more ethylene glycol, propylene glycol, lactic acid and / or glycolic acid. Generally, propylene glycol adds hydrophobicity, while ethylene glycol adds hydrophilicity. The lactic acid segment has a longer half-life than the glycolic acid segment. Blocked and random lactic acid-glycolic acid molecules, as well as ethylene glycol and propylene glycol, are known to be pharmaceutically acceptable in the art and can be modified or arranged to obtain desired half-lives and hydrophilicity. In certain aspects, these units may be flanked or interspersed on other molecules, including alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, etc., as needed to achieve appropriate drug properties.

[0055] Non-restrictive examples of compounds of chemical formula 1 according to the present invention are disclosed in Tables 1 to 14 below, with their names and chemical structures.

[0056] [Table 1-1]

[0057] [Table 1-2]

[0058] [Table 1-3]

[0059] [Table 1-4]

[0060] [Table 1-5]

[0061] Table 1-6

[0062] Table 1-7

[0063] Table 1-8

[0064] Table 1-9

[0065] Table 1-10

[0066] Table 1-11

[0067] Table 1-12

[0068] Table 1-13

[0069] Table 1-14

[0070] Table 1-15

[0071] Table 1-16

[0072] Table 1-17

[0073] Table 1-18

[0074] Table 1-19

[0075] Table 1-20

[0076] Table 1-21

[0077] Table 1-22

[0078] Table 1-23

[0079] Table 1-24

[0080] Table 1-25

[0081] Table 1-26

[0082] Table 1-27

[0083] Table 1-28

[0084] Table 1-29

[0085] Table 1-30

[0086] Table 1-31

[0087] Table 1-32

[0088] Table 1-33

[0089] Table 1-34

[0090] Table 1-35

[0091] Table 1-36

[0092] Table 1-37

[0093] Table 1-38

[0094] Table 1-39

[0095] Table 1-40

[0096] Table 1-41

[0097] Table 1-42

[0098] Table 1-43

[0099] Table 1-44

[0100] Table 1-45

[0101] Table 1-46

[0102] Table 1-47

[0103] Table 2-1

[0104] Table 2-2

[0105] Table 2-3

[0106] Table 2-4

[0107] Table 3-1

[0108] Table 3-2

[0109] Table 3-3

[0110] Table 3-4

[0111] Table 4-1

[0112] Table 4-2

[0113] Table 4-3

[0114] Table 4-4

[0115] Table 5-1

[0116] Table 5-2

[0117] Table 5-3

[0118] Table 5-4

[0119] Table 6-1

[0120] Table 6-2

[0121] Table 6-3

[0122] Table 6-4

[0123] Table 7-1

[0124] Table 7-2

[0125] Table 7-3

[0126] Table 7-4

[0127] Table 8-1

[0128] Table 8-2

[0129] Table 8-3

[0130] Table 8-4

[0131] Table 9-1

[0132] Table 9-2

[0133] Table 9-3

[0134] Table 9-4

[0135] Table 10-1

[0136] Table 10-2

[0137] Table 10-3

[0138] Table 10-4

[0139] Table 11-1

[0140] Table 11-2

[0141] Table 11-3

[0142] Table 11-4

[0143] Table 12-1

[0144] Table 12-2

[0145] Table 12-3

[0146] Table 12-4

[0147] Table 13-1

[0148] Table 13-2

[0149] Table 13-3

[0150] Table 13-4

[0151] Table 14-1

[0152] Table 14-2

[0153] [Table 14-3]

[0154] [Table 14-4]

[0155] Among the compounds described herein, for the purposes of the present invention, compounds 25, 31, 33, 34, 35, 38, 41, 45, 74, 75, 88, 89, 90, 91, 92, 93, 96, 108, 109, 114, 115, 116, 117, 122, 123, 124, 125, 134, 135, 137, 145, 148, 149, 150, 151, 152, 153, 162, 163 164, 165, 166, 167, 169, 170, 171, 174, 176, 178, 179, 182, 185, 189, 191, 193, 202, 204, 205, 217, 226, 236, 258, 259, 301, 307, 330, 353, 354, 378, 379, 393, 428, 429, etc. may be even more preferable, but are not limited thereto.

[0156] The compounds of the present invention may exist in the form of pharmaceutically acceptable salts. Useful salts include acid addition salts formed with pharmaceutically acceptable free acids. In the present invention, "pharmaceutically acceptable salt" means a salt form that is relatively non-toxic and harmless at concentrations that have an effective effect on patients, and includes any organic or inorganic addition salts of the said compound such that the side effects caused by the salt do not reduce the beneficial efficacy of the compound represented by chemical formula 1.

[0157] Acid addition salts are produced by conventional methods, for example, by dissolving a compound in an excess of acidic aqueous solution and precipitating the salt using a water-miscible organic solvent, such as methanol, ethanol, acetone, or acetonitrile. Alternatively, the same molar amount of the compound and an acid or alcohol (e.g., glycol monomethyl ether) in water can be heated, and then the mixture can be evaporated and dried, or the precipitated salt can be filtered by suction.

[0158] At that time, organic acids and inorganic acids can be used as free acids. As inorganic acids, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc. can be used, and are not limited to these. As organic acids, methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid, etc. can be used.

[0159] Furthermore, pharmaceutically acceptable metal salts can be produced using bases. Alkali metal salts or alkaline earth metal salts are obtained, for example, by dissolving a compound in an excess of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering out the insoluble compound salt, and then evaporating and drying the filtrate. In this process, sodium, potassium, or calcium salts are particularly suitable as pharmaceutically acceptable metal salts, but are not limited to these. Corresponding silver salts can be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (e.g., silver nitrate).

[0160] Unless otherwise specified, pharmaceutically acceptable salts of the compounds of the present invention include salts of acidic or basic groups that may be present in the compound of chemical formula 1. For example, pharmaceutically acceptable salts may include sodium, calcium, and potassium salts of the hydroxyl group, and other pharmaceutically acceptable salts of the amino group include hydrobromide, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate, dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate), and p-toluenesulfonate (tosylate) salts, which can be produced by salt production methods known in the art.

[0161] As for the salt of the compound of the present invention, any salt of the compound of chemical formula 1 that exhibits equivalent pharmacological activity to the compound of chemical formula 1 can be used without limitation, as long as it is pharmaceutically acceptable.

[0162] Furthermore, the compound represented by chemical formula 1 according to the present invention includes not only its pharmaceutically acceptable salts, but also solvates such as hydrates and all possible stereoisomers that can be produced therefrom without limitation. The solvates and stereoisomers of the compound represented by chemical formula 1 can be produced from the compound represented by chemical formula 1 using methods known to the art.

[0163] Furthermore, the compound represented by chemical formula 1 according to the present invention can be produced in crystalline or amorphous form, and if produced in crystalline form, it can be optionally hydrated or solvated. The present invention may include not only the stoichiometric hydrate of the compound represented by chemical formula 1, but also compounds containing various amounts of water. The solvates of the compound represented by chemical formula 1 according to the present invention include both stoichiometric and non-stoichiometric solvates.

[0164] A second aspect of the present invention provides a method for producing a compound of the first aspect or a pharmaceutically acceptable salt thereof, comprising: a first step of reacting a compound of chemical formula 4 with a derivative of A moiety having an amine group at one end and a protecting group at the other end, and deprotecting it to prepare a compound of chemical formula 5; a second step of reacting the compound of chemical formula 5 with a derivative of L1 moiety having a reactive functional group X2 at one end and a protecting group at the other end, and deprotecting it to prepare a compound of chemical formula 6; and a third step of reacting the compound of chemical formula 5 with a CRBN binder having a reactive functional group X3 at one end:

[0165] [ka]

[0166] [ka]

[0167] [ka]

[0168] In the aforementioned chemical formulas 4 to 6, X 1 Reach X3 is independently a halogen or hydroxyl, X 2 These are halogens, oxo, or hydroxyl compounds. The protecting group is tert-butoxycarbonyl. A' and L1' may be identical to A and L1, or in the form of salts thereof.

[0169] R1, A, and L1, which are not defined above, are as defined in the first mode.

[0170] in particular 、 The aforementioned CRBN binder is

[0171] [ka]

[0172] You may choose any one of the following from the group, but you are not limited to this.

[0173] For example, the first step can be carried out by using a compound in which X1 is a halogen, reacting it in a lower alcohol solvent at 70°C to 100°C, and then deprotecting it by treating it with a strong acid solution in an organic solvent, but is not limited thereto.

[0174] For example, the second stage is, i) Using a compound in which X2 is hydroxyl, react it with EDCI (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide), HOBt (hydroxybenzotriazole), and DIPEA (N,N-diisopropylethylamine) under an organic solvent at 15°C to 40°C, ii) Using a compound in which X2 is a halogen, react it in an organic solvent under basic conditions at 40°C to 80°C, iii) Using a compound in which X2 is oxo, react with DIPEA and sodium triacetoxyborohydride (NaBH(OAc)3) at 15°C to 40°C, or iv) Using a compound in which X2 is the oxo, react it with sodium borohydride (NaBH3CN) in the presence of acetic acid under a lower alcohol solvent at 15°C to 40°C. This can be carried out by deprotection by treatment with a strong acid solution in an organic solvent, but is not limited to this method.

[0175] Furthermore, depending on the type of linker to be introduced, the second step may, but is not limited to, performing two or more identical or different reactions selected from the four reactions described above in succession.

[0176] For example, the third stage is, i) Using a compound in which X3 is hydroxyl, react it with EDCI, HOBt and DIPEA in an organic solvent at 15°C to 40°C, ii) This can be carried out by reacting a compound in which X3 is a halogen with DIPEA in an organic solvent at 70°C to 100°C, but is not limited to this.

[0177] As described above, the reactions in each of the above steps can be carried out with a lower alcohol or an organic solvent. For example, the lower alcohol solvent is C 1-4 The alkyl alcohol may be methanol or ethanol, but is not limited to these. The organic solvent may also be dimethylformamide (DMF), dichloromethane (DCM), dimethyl sulfoxide (DMSO), etc., and may be used individually or in combination, but is not limited to these.

[0178] The strong acid solution may be a hydrochloric acid-containing solution, and the basic conditions may be achieved using potassium carbonate (K2CO3), but are not limited to these.

[0179] The specific reactions for carrying out the first to third steps described above are merely illustrative suggestions, and the scope of the present invention is not limited thereto; similar reactions known in the art can be used without limitation. Furthermore, the manufacturing method of the present invention may, but is not limited thereto, further include steps such as separation, purification, and / or washing after each step.

[0180] A third aspect of the present invention provides a composition comprising the compound of the first aspect or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0181] A fourth aspect of the present invention provides a pharmaceutical composition for inhibiting or degrading CDK2 (cyclin-dependent kinase 2), CDK9 (cyclin-dependent kinase 9), or both, comprising the compound of the first aspect or a pharmaceutically acceptable salt thereof as an active ingredient.

[0182] A fifth aspect of the present invention provides a pharmaceutical composition for the prevention or treatment of cancer or human immunodeficiency virus (HIV) infection, comprising the compound of the first aspect or a pharmaceutically acceptable salt thereof as an active ingredient.

[0183] The terms "compound of the first mode" and "pharmaceutically acceptable salt" in this invention are as described above.

[0184] In specific embodiments of the present invention, it was confirmed that the compounds exhibit the effect of degrading or inhibiting the activity of CDK2, CDK9, or both. This suggests that compositions containing the compounds of the present invention can efficiently suppress or degrade CDK2, CDK9, or both, and further suggest that they can be usefully used for the prevention or treatment of diseases induced by these enzymes.

[0185] In the present invention, "prevention" means any action that suppresses or delays the occurrence, spread, and recurrence of cancer or viral infections by administering the composition of the present invention, and "treatment" means any action that improves or beneficially alters the symptoms of the said disease by administering the composition of the present invention.

[0186] The diseases that can be prevented or treated by administering the pharmaceutical composition of the present invention are cancerous diseases or human immunodeficiency virus infection diseases, for example, the cancerous diseases include pseudomyxoma, intrahepatic biliary tract cancer, hepatoblastoma, liver cancer, thyroid cancer, colon cancer, testicular cancer, myelodysplastic syndrome, glioblastoma, oral cancer, lip cancer, mycosis fungoides, acute myeloid leukemia, acute lymphoblastic leukemia, basal cell carcinoma, ovarian epithelial carcinoma, ovarian germ cell carcinoma, Male breast cancer, brain cancer, pituitary adenoma, multiple myeloma, gallbladder cancer, biliary tract cancer, colorectal cancer, chronic myeloid leukemia, chronic lymphocytic leukemia, retinoblastoma, choroidal melanoma, diffuse large B-cell lymphoma, ampulla carcinoma of Vater, bladder cancer, peritoneal cancer, parathyroid cancer, adrenal cancer, nasal and paranasal sinus cancer, non-small cell lung cancer, non-Hodgkin lymphoma, tongue cancer, astrocytoma, small cell lung cancer, childhood brain cancer, childhood lymphoma Childhood leukemia, small intestine cancer, meningioma, esophageal cancer, glioma, neuroblastoma, renal pelvis cancer, kidney cancer, heart cancer, duodenal cancer, malignant soft tissue cancer, malignant bone cancer, malignant lymphoma, malignant mesothelioma, malignant melanoma, eye cancer, vulvar cancer, ureteral cancer, urethral cancer, cancer of unknown primary site, gastric lymphoma, gastric cancer, gastric carcinoid, gastrointestinal stromal cancer, Wilms' cancer, breast cancer, sarcoma, penile cancer, pharyngeal cancer, gestational trophoblastic disease, cervical cancer It may also be one or more selected from the group consisting of endometrial cancer, uterine sarcoma, prostate cancer, metastatic bone cancer, metastatic brain cancer, mediastinal cancer, rectal carcinoid cancer, vaginal cancer, spinal cord cancer, acoustic neuroma, pancreatic cancer, salivary gland cancer, Kaposi's sarcoma, Paget's disease, tonsil cancer, squamous cell carcinoma, lung adenocarcinoma, lung cancer, lung squamous cell carcinoma, skin cancer, anal cancer, rhabdomyosarcoma, laryngeal cancer, pleural cancer, and thymic cancer. Specifically, 、 The aforementioned cancerous diseases may include, but are not limited to, prostate cancer, lymphoma (e.g., B-cell lymphoma, Burkitt lymphoma, follicular lymphoma), glioblastoma, neuroblastoma, ovarian cancer, hepatocellular carcinoma, liver cancer, breast cancer, leukemia (e.g., chronic lymphocytic leukemia (CLL), acute myeloid leukemia), pancreatic cancer, colorectal cancer, lung cancer, colon cancer, or multiple myeloma. On the other hand, the human immunodeficiency virus infection disease may include, but is not limited to, acquired immune deficiency syndrome (AIDS). Furthermore, the aforementioned human immunodeficiency virus may include, but is not limited to, human immunodeficiency virus-1 (HIV-1), which is the most common and highly pathogenic variant.

[0187] Preferably, the pharmaceutical composition according to the present invention may contain, as an active ingredient, a compound represented by chemical formula 1, or a pharmaceutically acceptable salt thereof, in an amount of 0.1 to 75% by weight, more preferably 1 to 50% by weight, based on the total weight of the composition.

[0188] The compositions of the present invention may further contain pharmaceutically acceptable carriers, diluents, or excipients, and can be used in a variety of dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, and sterile injection solutions by conventional methods, depending on the intended use. They can be administered orally or through a variety of routes, including intravenous, intraperitoneal, subcutaneous, rectal, and local administration. Examples of suitable carriers, excipients, or diluents included in such compositions include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. Furthermore, the composition of the present invention may further contain fillers, anti-agglutinating agents, lubricants, wetting agents, fragrances, emulsifiers, preservatives, and the like.

[0189] Solid dosage forms for oral administration include tablets, pills, powders, granules, and capsules. Such solid dosage forms are formed by mixing the composition with at least one excipient, such as starch, calcium carbonate, sucrose, lactose, or gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.

[0190] Oral liquid formulations include suspensions, oral solutions, emulsions, and syrups. In addition to water and liquid paraffin, which are frequently used simple diluents, they may contain various excipients, such as humectants, sweeteners, fragrances, and preservatives.

[0191] Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, and suppositories. Examples of non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and ethyl oleate. Injectable esters such as the above are used. Suppository bases include vitepsol, macrogol, Twin 61, cocoa butter, lauric butter, and glycerogenous gelatin. On the other hand, injectable preparations may contain conventional additives such as solvents, isotonic agents, suspending agents, emulsifiers, stabilizers, and preservatives.

[0192] A sixth aspect of the present invention provides a method for preventing or treating cancer or human immunodeficiency virus infection, comprising the step of administering the pharmaceutical composition of the fifth aspect to an individual in need.

[0193] The terms "compound of the first mode" and "pharmaceutically acceptable salt" in this invention are as described above.

[0194] In this invention, the term "individual" means any animal, including humans, monkeys, cattle, horses, sheep, pigs, chickens, turkeys, quail, cats, dogs, mice, rats, rabbits, or guinea pigs, that have developed or are at risk of developing the aforementioned viral infection disease. By administering the pharmaceutical composition of this invention to an individual, the aforementioned disease can be effectively prevented or treated. The pharmaceutical composition of this invention can be administered in parallel with existing therapeutic agents.

[0195] In this invention, the term "administration" means providing a given substance to a patient by any suitable method, and the administration route of the compositions of this invention can be any common route as long as it can be delivered to the target tissue. This includes, but is not limited to, intraperitoneal, intravenous, intramuscular, subcutaneous, intradermal, oral, topical, intranasal, intrapulmonary, and rectal administration. The pharmaceutical compositions of this invention can also be administered by any device that can deliver the active substance to target cells. Preferred administration methods and formulations include intravenous injection, subcutaneous injection, intradermal injection, intramuscular injection, and intravenous infusion. Injectable preparations can be manufactured using aqueous solvents such as physiological saline and Ringer's solution, non-aqueous solvents such as vegetable oil, higher fatty acid esters (e.g., ethyl oleate), and alcohols (e.g., ethanol, benzyl alcohol, propylene glycol, glycerin), and may contain pharmaceutically acceptable carriers such as stabilizers to prevent deterioration (e.g., ascorbic acid, sodium bisulfite, sodium pyrosulfite, BHA, tocopherol, EDTA), emulsifiers, buffers for pH adjustment, and preservatives to inhibit microbial growth (e.g., phenylmercury nitrate, thimerosal, benzalkonium chloride, phenol, cresol, benzyl alcohol).

[0196] In this invention, the term "therapeutably effective amount" used in combination with the active ingredient means an effective amount for preventing or treating the target disease. Na transformation This refers to the compound, or the amount of its pharmaceutically acceptable salts.

[0197] The pharmaceutical compositions of the present invention may further contain, depending on the type of disease to be prevented or treated, known drugs used for the prevention or treatment of known diseases, in addition to the compound of the present invention or its pharmaceutically acceptable salts, as active ingredients. For example, when used for the prevention or treatment of viral infections, the compositions may further contain known drugs as active ingredients in addition to the compound of the present invention or its pharmaceutically acceptable salts, and may be used in combination with other known treatments for the treatment of these diseases.

[0198] At that time, the composition of the present invention is administered in a pharmaceutically effective amount. In the terminology of the present invention, "pharmaceutically effective amount" means an amount sufficient to treat the disease with a reasonable benefit / risk ratio applicable to medical treatment, without causing side effects. The effective dose level can be determined by factors including the patient's health condition, the type and severity of the disease, the activity of the drug, the sensitivity to the drug, the method of administration, the time of administration, the route of administration and elimination ratio, the duration of treatment, the drugs used in combination or concurrently, and other factors well known in the medical field. The composition of the present invention can be administered as an individual therapeutic agent, in combination with other therapeutic agents, sequentially or concurrently with conventional therapeutic agents, and in single or multiple doses. It is important to administer an amount that can obtain the maximum effect with the minimum amount without side effects, taking all of the above factors into consideration, and this can be easily determined by those skilled in the art.

[0199] For example, the dosage may be increased or decreased depending on the route of administration, the severity of the disease, gender, weight, age, etc., and therefore, the aforementioned dosage does not limit the scope of the present invention in any way.

[0200] in particular 、 In the composition of the present invention, the effective amount of the compound varies depending on the patient's age, sex, and weight. Generally, 1 to 100 mg per kg of body weight, preferably 5 to 60 mg, can be administered daily or every other day, or divided into 1 to 3 doses per day. However, the dosage can be increased or decreased depending on the route of administration, the severity of the disease, sex, weight, age, etc., and therefore, the aforementioned dosage does not limit the scope of the present invention by any means.

[0201] The present invention will be described in detail below with reference to examples and other details to aid in understanding the present invention. However, the examples of the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the examples below. The examples of the present invention are provided to give a more complete explanation of the present invention to a person with average skill in the art to which the present invention belongs.

[0202] Manufacturing of the compound of the present invention The synthesis process of some compounds of the present invention is described below. Compounds not mentioned below may be produced by the same method instead of the starting materials, intermediates, and / or reactants.

[0203] In the case of some intermediates, in particular the CDK inhibitor Moieti, they can be manufactured through the method disclosed in Korean Registered Patent No. 1893879, and by such reference the entirety of Korean Registered Patent No. 1893879 is incorporated herein.

[0204] <Substance> The structural formulas and names of the CRBN binder compounds used exemplary in specific examples of the present invention are listed below.

[0205] [ka]

[0206] CRBN Binder-1: (2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycine CRBN Binder-2: (2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycine CRBN Binder-3: 2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetic acid CRBN Binder-4: 2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetic acid CRBN Binder-5:2-(2,6-dioxopiperidine-3-yl)-5-fluoroisoindoline-1,3-dione CRBN Binder-6:2-(2,6-dioxopiperidine-3-yl)-4-fluoroisoindoline-1,3-dione CRBN Binder-7:2-(2,6-dioxopiperidine-3-yl)-5,6-difluoroisoindoline-1,3-dione CRBN Binder-8: 3-(2,4-Dioxotetrahydropyrimidine-1(2H)-yl)-4-methoxybenzoic acid CRBN Binder-9:2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetic acid CRBN Binder-10: 2-(3-(2,6-dioxopiperidine-3-yl)phenoxy)acetic acid CRBN Binder-11:3-(2,4-Dioxotetrahydropyrimidine-1(2H)-yl)benzofuran-6-carboxylic acid CRBN Binder-12: 2-(3-((1-(2,6-dioxopiperidine-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-yl)amino)phenyl)acetic acid CRBN Binder-13: 1-(1-(2,6-dioxopiperidine-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-yl)piperidine-4-carboxylic acid

[0207] Example 1: Synthesis of N-((1r,3r)-3-(6-((1-(6-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)acetamide)hexanoyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide (Compound 1)

[0208] [ka]

[0209] Step 1: Synthesis of tert-butyl 4-((9-((1s,3s)-3-(6-methylpicolinamide)cyclobutyl)-9H-purine-6-yl)amino)piperidine-1-carboxylate (intermediate A-1) N-((1s,3s)-3-(6-chloro-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide (Intermediate A, 583 mg, 1.70 mmol) was dissolved in ethanol (7 mL), and then tert-butyl 4-aminopiperidine-1-carboxylate (680 mg, 3.40 mmol) was added and the mixture was stirred at 90°C for 3 hours. Once the reaction was complete, the reaction product was concentrated under reduced pressure and separated and purified using silica gel column chromatography to obtain the target intermediate A-1 (Intermediate A-1, 698 mg, 1.19 mmol, 81%) as a white solid.

[0210] 1 H NMR (300 MHz, Chloroform-d) δ 8.84 (d, J = 8.5 Hz, 1H), 8.46 (s, 1H), 8.02 (d, J = 7.6 Hz, 1H), 7.89 (s, 1H), 7.74 (t, J = 7.7 Hz, 1H), 7.31 (d, J = 7.7 Hz, 1H), 5.68 (d, J = 8.1 Hz, 1H), 4.79 (t, J = 8.2 Hz, 1H), 4.60 (q, J = 8.1 Hz, 1H), 4.39 (s, 1H), 4.23-3.98 (m, 2H), 3.26-3.09 (m, 2H), 3.07-2.89 (m, 4H), 2.64 (s, 3H), 2.18-2.06 (m, 2H), 1.54 (s, 2H), 1.48 (s, 9H).

[0211] Step 1-1: Synthesis of 6-methyl-N-((1s,3s)-3-(6-(piperidine-4-ylamino)-9H-purine-9-yl)cyclobutyl)picolinamide hydrochloride (intermediate A-2) Intermediate A-1 (100 mg, 0.43 mmol) was dissolved in dichloromethane (2 mL), and 4N hydrochloric acid / 1,4-dioxene (1.08 mL) was added, followed by stirring at room temperature for 1 hour. The reaction product was concentrated under reduced pressure to obtain the target intermediate A-2 (143 mg, 0.35 mmol, quantified) as a white solid.

[0212] 1 H NMR (300 MHz, DMSO-d6) δ 9.70 (s, 1H), 9.14 (d, J = 9.0 Hz, 1H), 8.46 (s, 2H), 7.97-7.89 (m, 2H), 7.52 (dd, J = 5.8, 3.0 Hz, 1H), 4.93 (p, J = 8.4 Hz, 1H), 4.62-4.49 (m, 1H), 3.57 (s, 3H), 3.35 (s, 2H), 2.97-2.86 (m, 4H), 2.12-2.04 (m, 2H), 2.00-1.85 (m, 2H), 1.85-1.73 (m, 2H).

[0213] Step 2: Synthesis of tert-butyl(6-(4-((9-((1s,3s)-3-(6-methylpicolinamide)cyclobutyl)-9H-purine-6-yl)amino)piperidine-1-yl)-6-oxohexyl)carbamate (intermediate A-3) Intermediate A-2 (156 mg, 0.25 mmol), 6-((tert-butoxycarbonyl)amino)hexanoic acid (82 mg, 0.25 mmol), EDCI·HCl (53 mg, 0.28 mmol), and HOBt·H2O (40 mg, 0.28 mmol) were dissolved in DMF (1 mL), and DIPEA (0.2 mL, 1.25 mmol) was added. The mixture was then stirred at room temperature for 12 hours. The reaction product was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, the residue was dried over anhydrous magnesium sulfate, and the mixture was filtered. The filtrate was concentrated under reduced pressure and separated and purified using silica gel column chromatography to obtain the target intermediate A-3 (78 mg, 0.13 mmol, 51%) as a white solid.

[0214] 1H NMR (300 MHz, Chloroform-d) δ 8.85 (d, J = 8.5 Hz, 1H), 8.48 (s, 1H), 8.04 (d, J = 7.7 Hz, 1H), 7.92 (s, 1H), 7.77 (t, J = 7.7 Hz, 1H), 7.33 (d, J = 7.8 Hz, 1H), 5.87 (d, J = 8.0 Hz, 1H), 4.86-4.74 (m, 1H), 4.67-4.57 (m, 3H), 4.50 (s, 1H), 3.97-3.85 (m, 1H), 3.19-3.10 (m, 4H), 3.06-2.92 (m, 3H), 2.66 (s, 3H), 2.38 (t, J = 7.5 Hz, 2H), 2.23-2.12 (m, 2H), 1.68-1.65 (m, 2H), 1.56-1.48 (m, 4H), 1.46 (s, 9H), 1.44-1.38 (m, 2H), 1.32-1.21 (m, 2H).

[0215] Step 2-2: Synthesis of N-((1s,3s)-3-(6-((1-(6-aminohexanoyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide hydrochloride (intermediate A-4) Intermediate A-3 (77 mg, 0.11 mmol) was dissolved in dichloromethane (2 mL), and 4N hydrochloric acid / 1,4-dioxene (0.27 mL) was added. The mixture was then stirred at room temperature for 1 hour. The reaction product was concentrated under reduced pressure to obtain the target intermediate A-4 as a white solid.

[0216] 1H NMR (500 MHz, Methanol-d4) δ 8.75 (s, 1H), 8.57-8.41 (m, 3H), 8.00 (d, J = 8.3 Hz, 1H), 5.14-5.01 (m, 1H), 4.68-4.57 (m, 1H), 3.63-3.57 (m, 1H), 3.28 (s, 2H), 3.22 (t, J = 8.5 Hz, 2H), 3.20-3.14 (m, 2H), 3.09-3.01 (m, 3H), 2.98 (t, J = 7.7 Hz, 2H), 2.88 (s, 3H), 2.47-2.36 (m, 2H), 2.24-2.16 (m, 2H), 1.88 (s, 2H), 1.77-1.69 (m, 2H), 1.62 (s, 2H).

[0217] Step 3: Synthesis of N-((1r,3r)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)acetamide)hexanoyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide (Compound 1) Intermediate A-4 (10 mg, 0.019 mmol), (2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycine (6 mg, 0.019 mmol), EDCI·HCl (4 mg, 0.021 mmol), and HOBt·H2O (3 mg, 0.021 mmol) were dissolved in DMF (1 mL), and DIPEA (0.02 mL, 0.095 mmol) was added. The mixture was then stirred at room temperature for 12 hours. The reaction product was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, the residue was dried over anhydrous magnesium sulfate, and the mixture was filtered. The filtrate was concentrated under reduced pressure and separated and purified using silica gel column chromatography to obtain the target compound 1 (6.6 mg, 41%) as a yellow solid.

[0218] Example 2: Synthesis of N-((1r,3r)-3-(6-(((1-(6-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)acetamide)hexanoyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide (Compound 2)

[0219] [ka]

[0220] Compound 2 was synthesized in the same manner as in Example 1, except that (2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycine (CRBN binder 2) was used instead of CRBN binder 1.

[0221] Example 3: Synthesis of N-((1r,3r)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetamide)hexanoyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide (Compound 3)

[0222] [ka]

[0223] Compound 3 was synthesized in the same manner as in Example 1, except that 2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetic acid (CRBN binder 3) was used instead of CRBN binder 1.

[0224] Example 4: Synthesis of N-((1r,3r)-3-(6-((1-(6-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetamide)hexanoyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide (Compound 4)

[0225] [ka]

[0226] The synthesis was carried out in the same manner as in Example 1, except that 2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetic acid (CRBN binder 4) was used instead of CRBN binder 1.

[0227] Example 5: Synthesis of N-((1r,3r)-3-(6-((1-(6-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)amino)hexanoyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide (Compound 5)

[0228] [ka]

[0229] Intermediate A-4 (40 mg, 0.08 mmol) was dissolved in DMSO (1 mL), and 2-(2,6-dioxopiperidine-3-yl)-5-fluoroisoindoline-1,3-dione (22 mg, 0.08 mmol) and DIPEA (0.04 mL, 0.23 mmol) were added, followed by stirring at 90°C for 12 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, the residue was dried over anhydrous magnesium sulfate, and the mixture was filtered. The filtrate was concentrated and separated and purified by silica gel column chromatography to obtain the target compound 5 (6.7 mg, 11%) as a yellow solid.

[0230] Example 6: Synthesis of N-((1r,3r)-3-(6-((1-(6-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)hexanoyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide (Compound 6)

[0231] [ka]

[0232] The compound was synthesized in the same manner as compound 5, except that 2-(2,6-dioxopiperidine-3-yl)-4-fluoroisoindorin-1,3-dione (CRBN binder 6) was used instead of CRBN binder 5.

[0233] Compounds 7 to 153 were synthesized using the corresponding linker in the same or similar manner as in Examples 1 to 6. The following describes the synthesis methods of additional intermediates and compounds used, illustrating their significance. Compounds for which specific methods are not explicitly stated were synthesized using their corresponding intermediates and appropriate reactions.

[0234] Example 7: Synthesis of N-((1s,3s)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide (compound 154)

[0235] [ka]

[0236] Step 1: Synthesis of (1s,3s)-3-(6-chloro-9H-purine-9-yl)cyclobutan-1-amine hydrochloride (intermediate B-1) Intermediate B (tert-butyl(1s,3s)-3-(6-chloro-9H-purine-9-yl)cyclobutylcarbamate, 5.7 g, 17.6 mmol) was dissolved in dichloromethane (20 mL), and 4N hydrochloric acid / 1,4-dioxene (53 mmol) was added. The mixture was then stirred at room temperature for 1 hour. The reaction product was concentrated under reduced pressure to obtain the target intermediate B-1 (3.9 g) as a white solid.

[0237] 1H H NMR (300 MHz, DMSO) δ 9.21 (s, 1H), 8.79 (s, 1H), 8.57 (s, 3H), 5.04 (p, J = 8.5 Hz, 1H), 3.80-3.62 (m, 1H), 3.42-2.85 (m, 4H).

[0238] Step 2: Synthesis of N-((1s,3s)-3-(6-chloro-9H-purine-9-yl)cyclobutyl)acetamide (Intermediate B-2) Intermediate B-1 (650 mg, 2.4988 mmol) was dissolved in dichloromethane (10 mL), then TEA (1.044 mL) was added, followed by acetic anhydride (0.354 mL), and the mixture was stirred at room temperature. After the reaction was complete, the mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, the residue was dried over anhydrous magnesium sulfate, and the mixture was filtered. The filtrate was concentrated and separated and purified by silica gel column chromatography to obtain the target intermediate B-2 (170 mg, 22%).

[0239] 1 H NMR (500 MHz, Chloroform-d) δ 8.78 (s, 1H), 8.25 (s, 1H), 6.34 (d, J = 8.2 Hz, 1H), 4.85-4.76 (m, 1H), 4.50-4.40 (m, 1H), 3.15-3.08 (m, 2H), 2.96-2.89 (m, 2H), 2.07 (s, 3H).

[0240] Step 3: Synthesis of tert-butyl 4-(((9-((1s,3s)-3-acetamidocyclobutyl)-9H-purine-6-yl)amino)methyl)piperidine-1-carboxylate (intermediate B-3) Except for using intermediate B-2 (170 mg, 0.6398 mmol) and tert-butyl 4-(aminomethyl)piperidine-1-carboxylate (136 mg, 0.9597 mmol) as reaction products, the reaction was carried out in the same manner as in step 1 of Example 1, and after separation and purification, the target intermediate B-3 (256 mg, 90%) was obtained as a white solid.

[0241] 1 H NMR (500 MHz, Chloroform-d) δ 8.40 (s, 1H), 7.76 (s, 1H), 6.85 (d, J = 8.7 Hz, 1H), 5.85 (s, 1H), 4.73-4.63 (m, 1H), 4.53-4.42 (m, 1H), 4.15 (s, 2H), 3.59 (s, 2H), 3.54-3.50 (m, 1H), 3.13-3.05 (m, 2H), 2.91-2.83 (m, 2H), 2.72 (s, 2H), 2.07 (s, 3H), 1.83-1.78 (m, 2H), 1.47 (s, 9H), 1.30-1.20 (m, 2H).

[0242] Step 4: Synthesis of N-((1s,3s)-3-(6-((piperidine-4-ylmethyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide hydrochloride (intermediate B-4) The reaction was carried out in the same manner as in step 1-1 of Example 1, except that intermediate B-3 (250 mg, 0.5636 mmol) was used, and the target intermediate B-4 (214 mg) was obtained as a white solid.

[0243] 1H NMR (500 MHz, Methanol-d4) δ 8.54 (d, J = 4.3 Hz, 1H), 8.44 (d, J = 13.8 Hz, 1H), 4.33-4.25 (m, 1H), 4.19-4.13 (m, 1H), 3.64-3.58 (m, 1H), 3.51-3.44 (m, 2H), 3.10-3.01 (m, 4H), 2.84-2.75 (m, 2H), 2.16-2.09 (m, 2H), 2.03 (s, 3H), 1.63-1.62 (m, 3H), 1.62-1.57 (m, 1H).

[0244] Step 5: Synthesis of tert-butyl 4-((4-(((9-((1s,3s)-3-acetamidocyclobutyl)-9H-purine-6-yl)amino)methyl)piperidine-1-yl)methyl)piperidine-1-carboxylate (intermediate B-5) Intermediate B-4 (210 mg, 0.5527 mmol) was dissolved in dichloromethane (20 mL), then DIPEA (144 μL) and tert-butyl 4-formylpiperidine-1-carboxylate (188 mg, 0.8291 mmol) were added and the mixture was stirred. NaBH(OAC)3 (152 mg, 0.7185 mmol) was added and the mixture was stirred overnight at room temperature. Once the reaction was complete, the solvent was removed by reducing the pressure and concentration, and the mixture was separated and purified by silica gel column chromatography to obtain the target intermediate B-5 (0.264 g).

[0245] 1H NMR (500 MHz, Methanol-d4) δ 8.26 (d, J = 8.5 Hz, 2H), 4.83-4.74 (m, 1H), 4.33-4.24 (m, 1H), 4.08 (d, J = 13.2 Hz, 2H), 3.79-3.71 (m, 1H), 3.60-3.51 (m, 2H), 3.46 (d, J = 12.0 Hz, 2H), 3.28-3.21 (m, 1H), 3.02-2.94 (m, 2H), 2.82 (d, J = 6.9 Hz, 2H), 2.80-2.68 (m, 5H), 2.00 (s, 3H), 1.98 (s, 1H), 1.94 (s, 2H), 1.85-1.78 (m, 2H), 1.72-1.61 (m, 2H), 1.44 (s, 9H), 1.21-1.11 (m, 2H).

[0246] Step 6: Synthesis of N-((1s,3s)-3-(6-(((1-(piperidine-4-ylmethyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide hydrochloride (intermediate B-6) The reaction was carried out in the same manner as in step 2-1 of Example 1, except that intermediate B-5 (260 mg, 0.48 mmol) was used, and the target intermediate B-6 (211 mg) was obtained as a white solid.

[0247] 1 H NMR (500 MHz, Methanol-d4) δ 8.52 (s, 1H), 8.44 (d, J = 13.9 Hz, 1H), 4.31-4.22 (m, 1H), 3.78-3.71 (m, 2H), 3.61 (d, J = 6.7 Hz, 1H), 3.46 (d, J = 12.8 Hz, 2H), 3.16-3.00 (m, 8H), 2.81-2.73 (m, 2H), 2.32 (s, 1H), 2.15 (d, J = 15.0 Hz, 4H), 2.01 (s, 3H), 1.90-1.80 (m, 2H), 1.62 (s, 2H), 1.61-1.52 (m, 2H), 1.42-1.38 (m, 1H).

[0248] Step 7: Synthesis of N-((1s,3s)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide (compound 154) Except for using intermediate B-6 (20 mg, 0.0419 mmol) and CRBN binder 3 (16 mg, 0.0503 mmol), the reaction was carried out in the same manner as in step 3 of Example 1, followed by separation and purification to obtain the target compound 154 (6 mg, 20%) as a white solid.

[0249] Example 8: Synthesis of N-((1s,3s)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide (compound 155)

[0250] [ka]

[0251] It was synthesized in the same manner as compound 154, except that CRBN binder 4 was used instead of CRBN binder 3.

[0252] Example 9: Synthesis of N-((1s,3s)-3-(6-(((1-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide (Compound 156)

[0253] [ka]

[0254] The compound was synthesized in the same manner as compound 154, except that CRBN binder 1 was used instead of CRBN binder 3.

[0255] Example 10: Synthesis of N-((1s,3s)-3-(6-(((1-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide (Compound 157)

[0256] [ka]

[0257] The compound was synthesized in the same manner as compound 154, except that CRBN binder 2 was used instead of CRBN binder 3.

[0258] Example 11: Synthesis of N-((1s,3s)-3-(6-(((1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide (Compound 158)

[0259] [ka]

[0260] The synthesis was carried out in the same manner as in Example 5, except that intermediate B-6 was used instead of intermediate A-4.

[0261] Example 12: Synthesis of N-((1s,3s)-3-(6-(((1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide (Compound 159)

[0262] [ka]

[0263] It was synthesized in the same manner as compound 154, except that CRBN binder 6 was used instead of CRBN binder 3.

[0264] Compounds 160-185 were synthesized using the same or similar methods as those used for the synthesis of compounds 155-160, with the corresponding linkers.

[0265] Manufacturing Example 1: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(4-(piperidine-4-ylmethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide hydrochloride (intermediate C-6)

[0266] [ka]

[0267] Step 1: Synthesis of N-((1s,3s)-3-(6-chloro-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide (intermediate C-2) Intermediate B-1 (500 mg, 1.92 mmol) was dissolved in dichloroethane (15 mL), then 2-phenylacetic acid chloride (508 μL, 3.84 mmol) and DIPEA (1.4 mL, 7.68 mmol) were added, and the mixture was stirred at room temperature for 12 hours. After the reaction was complete, the mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, and the residue was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and separated and purified by silica gel column chromatography to obtain the target intermediate C-2 (265 mg, 40%).

[0268] 1 H NMR (500 MHz, CDCl3) δ 8.50 (s, 1H), 8.18 (s, 1H), 7.50 - 7.32 (m, 5H), 6.34 - 6.19 (m, 1H), 4.78 (p, J = 8.3 Hz, 1H), 4.48 (q, J = 8.2 Hz, 1H), 3.67 (s, 2H), 3.11 (m, 2H), 2.81 (m, 2H).

[0269] Step 2: Synthesis of tert-butyl 4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-carboxylate (intermediate C-3) Except for using intermediate C-2 (750 mg, 2.194 mmol) and tert-butyl 4-(4-aminophenyl)piperazine-1-carboxylate (1.1 g, 3.949 mmol), the reaction was carried out in the same manner as in Step 1 of Example 1, followed by separation and purification to obtain the target intermediate C-3 (1.0 g) as an ivory-colored solid.

[0270] 1H NMR (500 MHz, CDCl3) δ 8.25 (s, 1H), 7.78 (s, 1H), 7.71 - 7.54 (m, 3H), 7.42 - 7.37 (m, 5H), 7.01 - 6.92 (m, 2H), 6.69 (d, J = 8.6 Hz, 1H), 4.66 (p, J = 8.1 Hz, 1H), 4.46 (h, J = 8.1 Hz, 1H), 3.63 (s, 2H), 3.59 (t, J = 5.2 Hz, 4H), 3.11 (t, J = 5.2 Hz, 4H), 3.09 - 3.00 (m, 2H), 2.84 - 2.72 (m, 2H), 1.49 (s, 9H).

[0271] Step 3: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide hydrochloride (intermediate C-4) Except for using intermediate C-3 (1.0 g, 1.71 mmol), the reaction was carried out in the same manner as in step 1-1 of Example 1, and the target intermediate C-4 (850 mg) was obtained as a pale green solid.

[0272] 1 H NMR (500 MHz, CD3OD) δ 8.58 (s, 1H), 8.29 (s, 1H), 7.49 - 7.43 (m, 2H), 7.34 (m, 4H), 7.30 - 7.24 (m, 3H), 4.99 - 4.93 (m, 1H), 4.36 - 4.21 (m, 1H), 3.56 (m, 6H), 3.44 (m, 4H), 3.05 (m, 2H), 2.80 (m, 2H).

[0273] Step 4: Synthesis of tert-butyl 4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)methyl)piperidine-1-carboxylate (intermediate C-5) Intermediate C-4 (100 mg, 0.192 mmol) was dissolved in dichloromethane (10 mL), then DIPEA (100 μL, 0.576 mmol) and tert-butyl 4-formylpiperidine-1-carboxylate (82 mg, 0.385 mmol) were added and the mixture was stirred. NaBH(OAc)3 (142 mg, 0.672 mmol) was added and the mixture was stirred at room temperature for 12 hours. Once the reaction was complete, the solvent was removed by reducing the pressure and concentration, and the mixture was separated and purified by silica gel column chromatography to obtain the target intermediate C-5 (90 mg).

[0274] 1 H NMR (300 MHz, CD3OD) δ 8.32 (s, 1H), 8.25 (s, 1H), 7.70 - 7.56 (m, 2H), 7.41 - 7.18 (m, 5H), 7.10 - 6.96 (m, 2H), 4.81 (q, J = 8.5 Hz, 1H), 4.31 (p, J = 8.2 Hz, 1H), 4.09 (d, J = 13.1 Hz, 2H), 3.55 (s, 2H), 3.21 (t, J = 5.0 Hz, 4H), 3.00 (m, 2H), 2.76 (m, 2H), 2.65 (t, J = 5.1 Hz, 4H), 2.31 (d, J = 6.6 Hz, 2H), 1.81 (d, J = 12.1 Hz, 3H), 1.48 (s, 9H), 1.21 - 1.01 (m, 1H).

[0275] 5 steps: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(4-(piperidine-4-ylmethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide hydrochloride (intermediate C-6) Except for using intermediate C-5 (90 mg, 0.132 mmol), the reaction was carried out in the same manner as in step 2-1 of Example 1, and the target intermediate C-6 (75 mg) was obtained as a white solid.

[0276] 1H NMR (500 MHz, CD3OD) δ 8.59 (s, 1H), 8.30 (s, 1H), 7.54 - 7.42 (m, 2H), 7.36 - 7.33 (m, 4H), 7.31 - 7.23 (m, 3H), 4.99 - 4.94 (m, 1H), 4.34 - 4.24 (m, 1H), 3.99 (d, J = 13.0 Hz, 2H), 3.83 (d, J = 11.7 Hz, 2H), 3.56 (s, 2H), 3.52 - 3.36 (m, 6H), 3.28 (d, J = 6.7 Hz, 2H), 3.13 (m, 2H), 3.09 - 3.01 (m, 2H), 2.81 (m, 2H), 2.45 - 2.35 (m, 1H), 2.21 (d, J = 13.8 Hz, 2H), 1.70 - 1.58 (m, 2H).

[0277] Manufacturing Example 2: Synthesis of N-((1s,3s)-3-(6-((4-(4-(7-Azaspiro[3,5]nonan-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (intermediate C-8)

[0278] [ka]

[0279] Step 1: Synthesis of tert-butyl 2-(4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate (intermediate C-7) Intermediate C-7 was synthesized using the same method as in step 4 of manufacturing example 1.

[0280] 1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 8.47 (d, J = 7.7 Hz, 1H), 8.40 (s, 1H), 8.32 (s, 1H), 7.72 (d, J = 8.7 Hz, 2H), 7.34 - 7.20 (m, 5H), 6.91 (d, J = 9.0 Hz, 2H), 4.76 (p, J = 8.6 Hz, 1H), 4.16 (h, J = 8.2 Hz, 1H), 3.43 (s, 2H), 3.29 (t, J = 5.7 Hz, 2H), 3.20 (m,2H), 3.09 (m, 4H), 2.85 (m, 2H), 2.71 (t, J = 7.7 Hz, 1H), 2.67 - 2.57 (m, 2H), 2.38 (m, 4H), 1.98 (t, J = 9.4 Hz, 2H), 1.57 (t, J = 9.9 Hz, 2H), 1.49 (t, J = 5.6 Hz, 2H).

[0281] Step 2: Synthesis of N-((1s,3s)-3-(6-((4-(4-(7-azaspiro[3,5]nonan-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (intermediate C-8) Intermediate C- 8 They were synthesized.

[0282] 1H NMR (500 MHz, DMSO-d6) δ 11.71 (s, 1H), 10.33 (s, 1H), 8.79 (s, 2H), 8.68 (s, 1H), 8.60 (d, J = 7.6 Hz, 1H), 8.38 (s, 1H), 7.71 (d, J = 8.3 Hz, 2H), 7.35 - 7.28 (m, 4H), 7.24 (t, J = 6.8 Hz, 1H), 7.05 (d, J = 8.8 Hz, 2H), 4.80 (p, J = 8.5 Hz, 1H), 4.17 (h, J = 8.1 Hz, 1H), 3.81 (d, J = 12.9 Hz, 4H), 3.44 (s, 3H), 3.41 (m, 1H), 3.18 (t, J = 12.4 Hz, 2H), 3.08 - 2.93 (m, 6H), 2.92 - 2.83 (m, 2H), 2.65 (m, 2H), 2.34 (m, 2H), 2.22 (t, J = 10.1 Hz, 2H), 1.82 (t, J = 5.7 Hz, 2H), 1.75 (t, J = 5.7 Hz, 2H).

[0283] Manufacturing Example 3: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(4-(2-(piperidine-4-yl)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide hydrochloride (intermediate C-10)

[0284] [ka]

[0285] Step 1: Synthesis of tert-butyl 4-(2-oxo-2-(4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)ethyl)piperidine-1-carboxylate (intermediate C-9) The reaction was carried out in the same manner as in step 2-1 of Example 1, except that intermediate C-4 (100 mg, 0.192 mmol) and 2-(1-(tert-butoxycarbonyl)piperidine-4-yl)acetic acid (56 mg, 0.231 mmol) were used. The mixture was then separated and purified to obtain the target intermediate C-9 (105 mg, 79%) as a white solid.

[0286] 1 H NMR (400 MHz, CD3OD) δ 8.33 (s, 1H), 8.26 (s, 1H), 7.67 (d, J = 9.0 Hz, 2H), 7.34 (m, 4H), 7.31 - 7.22 (m, 1H), 7.11 - 7.03 (m, 2H), 4.83 (m, 1H), 4.31 (m, 1H), 4.09 (d, J = 13.2 Hz, 2H), 3.77 (m, 4H), 3.55 (s, 2H), 3.18 (dt, J = 16.0, 5.2 Hz, 4H), 3.01 (m, 2H), 2.77 (m, 2H), 2.42 (d, J = 7.0 Hz, 2H), 2.00 (m, 1H), 1.82 - 1.70 (m, 2H), 1.47 (s, 9H), 1.19 (m, 2H).

[0287] Step 2: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(4-(2-(piperidine-4-yl)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide hydrochloride (intermediate C-10) Intermediate C- 10 They were synthesized.

[0288] 1H NMR (400 MHz, CD3OD) δ 8.63 (s, 1H), 8.36 (s, 1H), 7.61 (d, J = 8.9 Hz, 1H), 7.46 (d, J = 9.0 Hz, 2H), 7.34 (m, 4H), 7.30 - 7.24 (m, 1H), 4.98 - 4.93 (m, 1H), 4.28 (m, 1H), 3.91 (m, 4H), 3.54 (m, 4H), 3.48 (t, J = 5.1 Hz, 1H), 3.42 (m, 2H), 3.12 - 2.99 (m, 4H), 2.80 (m, 2H), 2.53 (d, J = 6.8 Hz, 2H), 2.24 - 2.13 (m, 1H), 2.06 (d, J = 14.0 Hz, 2H), 1.61 - 1.45 (m, 2H).

[0289] Manufacturing Example 4: Synthesis of N-((1s,3s)-3-(6-((4-(4-(((1r,4r)-4-(aminomethyl)cyclohexyl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (intermediate C-12)

[0290] [ka]

[0291] Step 1: Synthesis of tert-butyl(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)methyl)cyclohexyl)methyl)carbamate (intermediate C-11) Intermediate C-4 (30 mg, 0.0577 mmol) was dissolved in DMF (5 mL), then tert-butyl(((1r,4r)-4-(iodomethyl)cyclohexyl)methyl)carbamate (24 mg, 0.0693 mmol) and potassium carbonate (20 mg, 0.144 mmol) were added, and the mixture was stirred at 70°C for 12 hours. The reaction product was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, the residue was dried over anhydrous magnesium sulfate, and the mixture was filtered. The filtrate was concentrated under reduced pressure, separated and purified using silica gel column chromatography, and the target intermediate C-11 (17 mg, 34%) was obtained as a white solid.

[0292] 1 H NMR (400 MHz, CDCl3) δ 8.27 (s, 1H), 7.83 (s, 1H), 7.70 - 7.60 (m, 3H), 7.46 - 7.31 (m, 5H), 6.97 (d, J = 8.6 Hz, 2H), 6.78 (d, J = 8.6 Hz, 1H), 4.67 (m, 2H), 4.47 (p, J = 8.1 Hz, 1H), 3.64 (s, 2H), 3.42 (m, 3H), 3.17 - 2.73 (m, 10H), 2.52 (s, 2H), 2.02 (m, 3H), 1.87 - 1.56 (m, 4H), 1.46 (s, 9H), 1.16 - 0.85 (m, 4H).

[0293] Step 2: Synthesis of N-((1s,3s)-3-(6-((4-(4-(((1r,4r)-4-(aminomethyl)cyclohexyl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (intermediate C-12) Intermediate C- 12 They were synthesized.

[0294] 1H NMR (500 MHz, CD3OD) δ 8.57 (s, 1H), 8.29 (m, 1H), 7.55 - 7.23 (m, 9H), 4.28 (m, 1H), 3.98 (d, J = 10.3 Hz, 2H), 3.84 - 3.59 (m, 5H), 3.55 (s, 2H), 3.41 (m, 3H), 3.17 (d, J = 6.8 Hz, 2H), 3.05 (m, 2H), 2.82 (m, 4H), 2.00 (m, 4H), 1.69 (m, 1H), 1.26 (m, 5H).

[0295] Manufacturing Example 5: Synthesis of 6-methyl-N-((1s,3s)-3-(6-((3-(4-(piperidine-4-ylmethyl)piperazine-1-yl)propyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide hydrochloride (intermediate D-4)

[0296] [ka]

[0297] Step 1: Synthesis of tert-butyl 4-(3-((9-((1s,3s)-3-(6-methylpicolinamide)cyclobutyl)-9H-purine-6-yl)amino)propyl)piperazine-1-carboxylate (intermediate D-1) Intermediate D-1 was synthesized by reacting in the same manner as in step 1 of Example 1, except that tert-butyl 4-(3-aminophenyl)piperazine-1-carboxylate was used.

[0298] 1H NMR (400 MHz, CDCl3) δ 8.79 (d, J = 8.6 Hz, 1H), 8.37 (s, 1H), 7.94 (d, J = 7.7 Hz, 1H), 7.80 (s, 1H), 7.67 (t, J = 7.7 Hz, 1H), 7.23 (d, J = 7.7 Hz, 1H), 7.00 (s, 1H), 4.71 (p, J = 8.3 Hz, 1H), 4.53 (h, J = 8.2 Hz, 1H), 3.67 (m, 2H), 3.52 (t, J = 5.1 Hz, 4H), 3.18 - 3.03 (m, 2H), 2.88 (m, 2H), 2.57 (m, 5H), 2.51 - 2.38 (m, 4H), 1.87 (p, J = 6.5 Hz, 2H), 1.40 (s, 9H).

[0299] Step 2: Synthesis of 6-methyl-N-((1s,3s)-3-(6-((3-(piperazine-1-yl)propyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide (intermediate D-2) Intermediate D-2 was synthesized in the same manner as in step 1-1 of Example 1.

[0300] 1 H NMR (300 MHz, CD3OD) δ 8.33 (s, 1H), 8.29 (s, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.85 (t, J = 7.7 Hz, 1H), 7.46 (dd, J = 7.6, 1.2 Hz, 1H), 4.88 (m, 1H), 4.61 (p, J = 8.2 Hz, 1H), 3.68 (m, 2H), 3.15 - 3.03 (m, 2H), 2.98 (m, 2H), 2.89 (t, J = 5.0 Hz, 4H), 2.66 (s, 3H), 2.61 - 2.41 (m, 6H), 1.93 (p, J = 6.9 Hz, 2H).

[0301] Step 3: Synthesis of tert-butyl 4-((4-(3-((9-((1s,3s)-3-(6-methylpicolinamide)cyclobutyl)-9H-purine-6-yl)amino)propyl)piperazine-1-yl)methyl)piperidine-1-carboxylate (intermediate D-3) Intermediate D-2 (150 mg, 0.333 mmol) was dissolved in methanol (25 mL), then tert-butyl 4-formylpiperidine-1-carboxylate (106 mg, 0.50 mmol) and acetic acid (0.5 mL) were added and the mixture was stirred for 30 minutes. NaBH3CN (125 mg, 1.98 mmol) was slowly added to the reaction solution, and the mixture was stirred at room temperature for 12 hours. The reaction solution was concentrated under reduced pressure, diluted with saturated sodium bicarbonate solution, and extracted with ethyl acetate. The filtrate was concentrated under reduced pressure and separated and purified using silica gel column chromatography to obtain the target intermediate D-3 (138 mg, 90%) as a white solid (138 mg, 90% yield).

[0302] 1 H NMR (500 MHz, CD3OD) δ 8.34 (s, 1H), 8.30 (s, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.86 (t, J = 7.8 Hz, 1H), 7.47 (d, J = 7.8 Hz, 1H), 4.89 (m, 1H), 4.61 (m, 1H), 4.07 (d, J = 13.2 Hz, 2H), 3.67 (m, 2H), 3.14 - 3.05 (m, 3H), 2.97 (m, 3H), 2.62 (m, 14H), 2.25 (d, J = 6.5 Hz, 2H), 1.94 (m, 2H), 1.77 (d, J = 12.2 Hz, 3H), 1.47 (s, 9H), 1.15 - 0.99 (m, 2H).

[0303] Step 4: Synthesis of 6-methyl-N-((1s,3s)-3-(6-((3-(4-(piperidine-4-ylmethyl)piperazine-1-yl)propyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide hydrochloride (intermediate D-4) Intermediate D-4 was synthesized using the same method as in step 5 of manufacturing example 1.

[0304] 1 H NMR (500 MHz, CD3OD) δ 8.88 (s, 0.5H), 8.73 (s, 0.5H), 8.64 - 8.43 (m, 3H), 8.07 (d, J = 7.8 Hz, 1H), 5.17 - 5.01 (m, 1H), 4.64 (m, 1H), 4.29 (m, 1H), 3.84 (m, 9H), 3.58 - 3.42 (m, 4H), 3.21 - 3.02 (m, 6H), 2.91 (s, 3H), 2.37 (m, 3H), 2.24 (d, J = 14.2 Hz, 2H), 1.59 (m, 2H).

[0305] Manufacturing Example 6: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(4-(3-(piperazin-1-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide hydrochloride (intermediate C-14)

[0306] [ka]

[0307] Step 1: Synthesis of tert-butyl 4-(3-(4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)propyl)piperazine-1-carboxylate (intermediate C-13) Intermediate C-13 was synthesized using the same method as in step 1 of manufacturing example 4.

[0308] 1H NMR (300 MHz, CD3OD) δ 8.32 (s, 1H), 8.25 (s, 1H), 7.65 (d, J = 9.0 Hz, 2H), 7.38 - 7.19 (m, 5H), 7.13 - 6.97 (m, 2H), 4.81 (q, J = 8.6 Hz, 1H), 4.31 (p, J = 8.2 Hz, 1H), 3.55 (s, 2H), 3.47 (t, J = 4.8 Hz, 4H), 3.23 (t, J = 5.0 Hz, 4H), 3.06 - 2.94 (m, 2H), 2.84 - 2.64 (m, 6H), 2.47 (m, 8H), 1.80 (m, 2H), 1.48 (s, 9H).

[0309] Step 2: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(4-(3-(piperazin-1-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide hydrochloride (intermediate C-14) Intermediate C-14 was synthesized using the same method as in step 5 of manufacturing example 1.

[0310] 1 H NMR (400 MHz, CD3OD) δ 8.57 (s, 1H), 8.29 (s, 1H), 7.46 (d, J = 8.7 Hz, 2H), 7.33 (m, 4H), 7.27 (m, 3H), 5.00 - 4.93 (m, 1H), 4.28 (m, 1H), 4.02 (s, 3H), 3.87 - 3.65 (m, 14H), 3.62 - 3.58 (m, 2H), 3.55 (s, 2H), 3.47 (m, 5H), 3.05 (m, 2H), 2.80 (m, 2H), 2.55 - 2.37 (m, 2H).

[0311] Manufacturing Example 7: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(4-(2-(piperidine-4-yloxy)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide hydrochloride (intermediate C-16)

[0312] [ka]

[0313] Step 1: Synthesis of tert-butyl 4-(2-(4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)ethoxy)piperidine-1-carboxylate (intermediate C-15) Intermediate C- 15 They were synthesized.

[0314] 1 H NMR (300 MHz, CD3OD) δ 8.32 (s, 1H), 8.26 (s, 1H), 7.65 (d, J = 8.9 Hz, 2H), 7.41 - 7.23 (m, 5H), 7.04 (d, J = 9.1 Hz, 2H), 4.82 (m, 1H), 4.31 (m, 1H), 3.83 - 3.67 (m, 6H), 3.55 (s, 3H), 3.23 (t, J = 5.1 Hz, 4H), 3.17 (m, 2H), 3.07 - 2.92 (m, 2H), 2.82 - 2.65 (m, 8H), 1.95 - 1.82 (m, 2H), 1.54 (m, 2H), 1.48 (s, H).

[0315] Step 2: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(4-(2-(piperidine-4-yloxy)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide hydrochloride (intermediate C-16) Intermediate C-16 They were synthesized.

[0316] 1 H NMR (400 MHz, CD3OD) δ 8.57 (s, 1H), 8.29 (s, 1H), 7.46 (d, J = 8.7 Hz, 2H), 7.33 (m, 4H), 7.28 - 7.22 (m, 3H), 4.95 (q, J = 8.2, 7.7 Hz, 1H), 4.28 (h, J = 7.8, 7.4 Hz, 1H), 3.99 (t, J = 5.0 Hz, 4H), 3.89 - 3.74 (m, 4H), 3.69 (m, 1H), 3.55 (m, 4H), 3.48 - 3.38 (m, 5H), 3.16 (m, 2H), 3.09 - 2.98 (m, 2H), 2.79 (m, 2H), 2.12 (m, 2H), 1.99 (m, 2H).

[0317] Manufacturing Example 8: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(4-(3-(piperidine-4-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide hydrochloride (intermediate C-18)

[0318] [ka]

[0319] Step 1: Synthesis of tert-butyl 4-(3-(4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)propyl)piperidine-1-carboxylate (intermediate C-17) Intermediate C-17 was synthesized using the same method as in step 1 of manufacturing example 4.

[0320] 1H NMR (300 MHz, CD3OD) δ 8.33 (s, 1H), 8.26 (s, 1H), 7.66 (d, J = 8.9 Hz, 2H), 7.34 (m, 4H), 7.31 - 7.22 (m, 1H), 7.05 (d, J = 9.1 Hz, 2H), 4.81 (q, J = 8.1 Hz, 1H), 4.29 (q, J = 8.2 Hz, 1H), 4.08 (d, J = 12.9 Hz, 2H), 3.55 (s, 2H), 3.24 (t, J = 5.0 Hz, 4H), 3.01 (m, 2H), 2.86 - 2.67 (m, 8H), 2.53 - 2.43 (m, 2H), 1.74 (d, J = 13.0 Hz, 2H), 1.68 - 1.57 (m, 3H), 1.47 (s, 8H), 1.31 (m, 2H), 1.09 (m, 2H).

[0321] Step 2: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(4-(3-(piperidine-4-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide hydrochloride (intermediate C-18) Intermediate C-18 was synthesized using the same method as in step 1 of manufacturing example 4.

[0322] 1H NMR (400 MHz, CD3OD) δ 8.59 (s, 1H), 8.30 (s, 1H), 7.46 (d, J = 8.8 Hz, 2H), 7.33 (m, 4H), 7.27 (m, 3H), 4.95 (m, 1H), 4.29 (p, J = 8.2 Hz, 1H), 4.00 (d, J = 9.7 Hz, 2H), 3.76 (m, 3H), 3.69 (m, 1H), 3.64 - 3.58 (m, 1H), 3.56 (s, 2H), 3.43 (d, J = 12.9 Hz, 2H), 3.31 (m, 1H), 3.26 (m, 2H), 3.09 - 2.97 (m, 4H), 2.80 (m, 2H), 2.03 (d, J = 14.1 Hz, 2H), 1.93 (m, 2H), 1.73 (m, 1H), 1.47 (m, 4H).

[0323] Manufacturing Example 9: Synthesis of N-((1s,3s)-3-(6-((4-(4-(6-azaspiro[3,4]octan-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (intermediate C-20)

[0324] [ka]

[0325] Step 1: Synthesis of tert-butyl 2-(4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)-6-azaspiro[3,4]octane-6-carboxylate (intermediate C-19) Intermediate C-19 was synthesized using the same method as in step 2 of manufacturing example 5.

[0326] 1H NMR (400 MHz, CD3OD) δ 8.32 (s, 1H), 8.25 (s, 1H), 7.65 (d, J = 8.9 Hz, 2H), 7.34 (m, 4H), 7.27 (m, 1H), 7.04 (d, J = 8.7 Hz, 2H), 4.81 (m, 1H), 4.31 (p, J = 8.2 Hz, 1H), 3.55 (s, 2H), 3.37 (m, 3H), 3.24 (m, 5H), 3.07 - 2.95 (m, 2H), 2.87 (m, 1H), 2.77 (m, 2H), 2.59 (t, J = 4.9 Hz, 4H), 2.16 (m, 2H), 1.98 (m, 3H), 1.89 (m, 1H), 1.48 (m, 9H).

[0327] Two steps: Synthesis of N-((1s,3s)-3-(6-((4-(4-(6-azaspiro[3,4]octan-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (intermediate C-20) Intermediate C-20 was synthesized using the same method as in step 5 of manufacturing example 1.

[0328] 1 H NMR (400 MHz, CD3OD) δ 8.57 (s, 1H), 8.29 (s, 1H), 7.48 - 7.42 (m, 2H), 7.33 (m, 4H), 7.27 (d, J = 9.0 Hz, 2H), 5.00 - 4.92 (m, 1H), 4.28 (p, J = 8.2 Hz, 1H), 4.07 - 3.86 (m, 4H), 3.62 (m, 2H), 3.55 (s, 2H), 3.42 - 3.35 (m, 4H), 3.16 (t, J = 11.8 Hz, 2H), 3.09 - 2.99 (m, 2H), 2.83 - 2.59 (m, 5H), 2.54 (t, J = 10.1 Hz, 1H), 2.21 (q, J = 7.2 Hz, 2H).

[0329] Manufacturing Example 10: Synthesis of N-((1s,3s)-3-(6-((4-(4-(7-(azetidine-3-yl)-7-azaspiro[3,5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (intermediate C-24)

[0330] [ka]

[0331] Step 1: Synthesis of tert-butyl 2-(4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate (intermediate C-21) Intermediate C-21 was synthesized using the same method as in step 2 of manufacturing example 5.

[0332] 1 H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 8.47 (d, J = 7.7 Hz, 1H), 8.40 (s, 1H), 8.32 (s, 1H), 7.72 (d, J = 8.7 Hz, 2H), 7.34 - 7.20 (m, 5H), 6.91 (d, J = 9.0 Hz, 2H), 4.76 (p, J = 8.6 Hz, 1H), 4.16 (h, J = 8.2 Hz, 1H), 3.43 (s, 2H), 3.29 (t, J = 5.7 Hz, 2H), 3.20 (m,2H), 3.09 (m, 4H), 2.85 (m, 2H), 2.71 (t, J = 7.7 Hz, 1H), 2.67 - 2.57 (m, 2H), 2.38 (m, 4H), 1.98 (t, J = 9.4 Hz, 2H), 1.57 (t, J = 9.9 Hz, 2H), 1.49 (t, J = 5.6 Hz, 2H).

[0333] Step 2: Synthesis of N-((1s,3s)-3-(6-((4-(4-(7-azaspiro[3,5]nonan-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (intermediate C-22) Intermediate C-22 was synthesized using the same method as in step 5 of manufacturing example 1.

[0334] 1 H NMR (500 MHz, DMSO-d6) δ 11.71 (s, 1H), 10.33 (s, 1H), 8.79 (s, 2H), 8.68 (s, 1H), 8.60 (d, J = 7.6 Hz, 1H), 8.38 (s, 1H), 7.71 (d, J = 8.3 Hz, 2H), 7.35 - 7.28 (m, 4H), 7.24 (t, J = 6.8 Hz, 1H), 7.05 (d, J = 8.8 Hz, 2H), 4.80 (p, J = 8.5 Hz, 1H), 4.17 (h, J = 8.1 Hz, 1H), 3.81 (d, J = 12.9 Hz, 4H), 3.44 (s, 3H), 3.41 (m, 1H), 3.18 (t, J = 12.4 Hz, 2H), 3.08 - 2.93 (m, 6H), 2.92 - 2.83 (m, 2H), 2.65 (m, 2H), 2.34 (m, 2H), 2.22 (t, J = 10.1 Hz, 2H), 1.82 (t, J = 5.7 Hz, 2H), 1.75 (t, J = 5.7 Hz, 2H).

[0335] Step 3: Synthesis of tert-butyl3-(2-(4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)-7-azaspiro[3,5]nonane-7-yl)azetidine-1-carboxylate (intermediate C-23) Intermediate C-23 was synthesized using the same method as in step 4 of manufacturing example 1.

[0336] 1H NMR (400 MHz, CD3OD) δ 8.32 (s, 1H), 8.25 (s, 1H), 7.66 (d, J = 8.8 Hz, 2H), 7.40 - 7.18 (m, 5H), 7.04 (d, J = 8.8 Hz, 2H), 4.81 (q, J = 8.3 Hz, 1H), 4.31 (m, 1H), 3.97 (m, 2H), 3.78 (m, 2H), 3.55 (s, 2H), 3.24 (m, 4H), 3.13 - 2.95 (m, 3H), 2.90 (t, J = 8.0 Hz, 1H), 2.76 (m, 2H), 2.62 (m, 4H), 2.47 - 2.21 (m, 2H), 2.09 (m, 2H), 1.73 (m, 4H), 1.65 (t, J = 5.5 Hz, 2H), 1.46 (s, 9H), 1.39 (d, J = 6.4 Hz, 2H).

[0337] Step 4: Synthesis of N-((1s,3s)-3-(6-((4-(4-(7-(azetidine-3-yl)-7-azaspiro[3,5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (intermediate C-24) Intermediate C-24 was synthesized using the same method as in step 5 of manufacturing example 1.

[0338] 1H NMR (400 MHz, CD3OD) δ 8.55 (s, 1H), 8.28 (s, 1H), 7.45 (d, J = 8.8 Hz, 2H), 7.38 - 7.18 (m, 7H), 4.95 (m, 2H), 4.71 (m, 2H), 4.47 - 4.35 (m, 3H), 4.28 (p, J = 8.4 Hz, 1H), 4.00 (d, J = 13.4 Hz, 2H), 3.89 (m, 1H), 3.76 (t, J = 5.7 Hz, 1H), 3.72 - 3.58 (m, 6H), 3.55 (s, 2H), 3.19 - 2.99 (m, 5H), 2.79 (m, 2H), 2.58 (m, 1H), 2.39 (m, 2H), 2.23 - 2.05 (m, 4H).

[0339] Manufacturing Example 11: Synthesis of N-((1s,3s)-3-(6-((4-(4-(7-(azetidine-3-ylmethyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (intermediate C-25)

[0340] [ka]

[0341] Step 1: Synthesis of tert-butyl 3-((2-(4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)-7-azaspiro[3.5]nonane-7-yl)methyl)azetidine-1-carboxylate (intermediate C-25) Intermediate C-25 was synthesized using the same method as in step 1 of manufacturing example 4.

[0342] 1H NMR (300 MHz, CD3OD) δ 8.32 (s, 1H), 8.26 (s, 1H), 7.65 (d, J = 9.0 Hz, 2H), 7.34 (m, 4H), 7.27 (m, 1H), 7.04 (d, J = 9.0 Hz, 2H), 4.83 (m, 1H), 4.63 (s, 4H), 4.31 (p, J = 8.5 Hz, 1H), 4.06 (t, J = 8.4 Hz, 2H), 3.69 - 3.59 (m, 2H), 3.55 (s, 2H), 3.23 (m, 4H), 3.01 (m, 2H), 2.89 - 2.66 (m, 6H), 2.59 (m, 4H), 2.46 (m, 2H), 2.16 - 2.00 (m, 2H), 1.74 (m, 3H), 1.66 (t, J = 5.8 Hz, 2H), 1.45 (s, 9H).

[0343] Step 2: Synthesis of N-((1s,3s)-3-(6-((4-(4-(7-(azetidine-3-ylmethyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide (intermediate C-26) Intermediate C-26 was synthesized using the same method as in step 5 of manufacturing example 1.

[0344] 1 1H NMR (400 MHz, CD3OD) δ 8.56 (s, 1H), 8.28 (s, 1H), 7.46 (d, J = 8.5 Hz, 2H), 7.33 (m, 4H), 7.26 (d, J = 8.6 Hz, 3H), 4.89 (m, 2H), 4.26 (m, 4H), 4.15 - 3.95 (m, 4H), 3.90 (m, 1H), 3.76 (m, 1H), 3.72 - 3.60 (m, 5H), 3.54 (m, 4H), 3.45 (m, 2H), 3.10 (m, 6H), 2.79 (m, 2H), 2.61 (m, 1H), 2.40 (m, 3H), 2.08 (m, 4H).

[0345] Manufacturing Example 12: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(1-(piperidine-4-ylmethyl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide hydrochloride (intermediate E-4)

[0346] [ka]

[0347] Step 1: Synthesis of tert-butyl 4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperidine-1-carboxylate (intermediate E-1) Intermediate E-1 was synthesized using the same method as in step 2 of manufacturing example 1.

[0348] 1 H NMR (500 MHz, DMSO-d6) δ 9.83 (s, 1H), 8.48 (d, J = 7.7 Hz, 1H), 8.45 (s, 1H), 8.38 (s, 1H), 7.85 (d, J = 8.6 Hz, 2H), 7.39 - 7.15 (m, 7H), 4.78 (p, J = 8.6 Hz, 1H), 4.16 (q, J = 8.1 Hz, 1H), 4.08 (m, 2H), 3.44 (s, 2H), 2.92 - 2.74 (m, 4H), 2.72 - 2.59 (m, 3H), 1.76 (d, J = 12.8 Hz, 2H), 1.50 (m, 2H), 1.43 (s, 9H).

[0349] Step 2: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide hydrochloride (intermediate E-2) Intermediate E-2 was synthesized using the same method as in step 3 of manufacturing example 1.

[0350] 1 H NMR (400 MHz, CD3OD) δ 8.36 (s, 1H), 8.26 (s, 1H), 7.77 - 7.68 (m, 2H), 7.38 - 7.22 (m, 7H), 4.85 - 4.74 (m, 1H), 4.30 (p, J = 8.3 Hz, 1H), 3.54 (s, 2H), 3.21 - 3.13 (m, 2H), 3.00 (m, 2H), 2.76 (m, 4H), 2.71 - 2.62 (m, 1H).

[0351] Step 3: Synthesis of tert-butyl 4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperidin-1-yl)methyl)piperidine-1-carboxylate (Intermediate E-3) Intermediate E-3 was synthesized in the same manner as in Step 4 of Preparation Example 1 described above.

[0352] 1 H NMR (400 MHz, CD3OD) δ 8.37 (s, 1H), 8.28 (s, 1H), 7.74 (d, J = 8.5 Hz, 2H), 7.34 (m, 4H), 7.28 (m, 3H), 4.85 - 4.76 (m, 1H), 4.30 (h, J = 7.9 Hz, 1H), 4.11 (d, J = 13.2 Hz, 2H), 3.55 (s, 2H), 3.19 (d, J = 11.5 Hz, 2H), 3.08 - 2.98 (m, 2H), 2.77 (m, 2H), 2.64 (m, 1H), 2.44 (d, J = 6.7 Hz, 2H), 2.31 (m, 2H), 1.93 - 1.74 (m, 7H), 1.48 (s, 9H), 1.14 (m, 2H).

[0353] Step 4: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(1-(piperidine-4-ylmethyl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide hydrochloride (intermediate E-4) Intermediate E-4 was synthesized using the same method as in step 5 of manufacturing example 1.

[0354] 1 H NMR (500 MHz, CD3OD) δ 8.61 (s, 1H), 8.32 (s, 1H), 7.58 (d, J = 8.6 Hz, 2H), 7.54 (d, J = 8.5 Hz, 2H), 7.34 (m, 4H), 7.30 - 7.23 (m, 1H), 4.99 - 4.93 (m, 1H), 4.33 - 4.23 (m, 1H), 3.82 (d, J = 12.0 Hz, 2H), 3.56 (s, 2H), 3.49 (d, J = 12.9 Hz, 2H), 3.28 - 3.18 (m, 4H), 3.16 - 2.99 (m, 5H), 2.81 (m, 2H), 2.41 - 2.29 (m, 3H), 2.19 (t, J = 16.3 Hz, 4H), 1.61 (m, 2H).

[0355] Manufacturing Example 13: Synthesis of N-((1s,3s)-3-(6-((4-(1-(7-azaspiro[3,5]nonan-2-yl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (intermediate E-6)

[0356] [ka]

[0357] Step 1: tert-butyl2-(4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperidine-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate (intermediate E-5) Intermediate E-5 was synthesized using the same method as in step 4 of manufacturing example 1.

[0358] 1 H NMR (400 MHz, CD3OD) δ 8.38 (s, 1H), 8.28 (s, 1H), 7.77 (d, J = 8.6 Hz, 2H), 7.34 (m, 4H), 7.32 - 7.24 (m, 3H), 4.85 - 4.78 (m, 1H), 4.36 - 4.25 (m, 1H), 3.55 (s, 2H), 3.42 (m, 1H), 3.37 (m, 2H), 3.26 (d, J = 11.3 Hz, 2H), 3.06 - 2.96 (m, 2H), 2.77 (m, H), 2.33 (m, 2H), 2.21 (t, J = 10.1 Hz, 2H), 2.06 - 1.77 (m, 7H), 1.63 (t, J = 5.6 Hz, 2H), 1.59 - 1.54 (m, 2H), 1.47 (s, 9H).

[0359] Step 2: Synthesis of N-((1s,3s)-3-(6-((4-(1-(7-azaspiro[3,5]nonan-2-yl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (intermediate E-6) Intermediate E-6 was synthesized using the same method as in step 5 of manufacturing example 1.

[0360] 1H NMR (500 MHz, CD3OD) δ 8.55 (s, 1H), 8.27 (s, 1H), 7.53 (d, J = 8.5 Hz, 2H), 7.50 (d, J = 8.6 Hz, 2H), 7.30 (m, 4H), 7.23 (m, 1H), 4.91 (m, 1H), 4.24 (p, J = 8.3 Hz, 1H), 3.80 - 3.71 (m, 1H), 3.61 (d, J = 11.9 Hz, 2H), 3.51 (s, 2H), 3.18 (t, J = 5.9 Hz, 2H), 3.12 (t, J = 5.7Hz, 2H), 3.06 - 2.93 (m, 5H), 2.76 (m, 2H), 2.41 (t, J = 10.3 Hz, 2H), 2.34 (t, J = 10.6 Hz, 2H), 2.17 (m, 4H), 1.92 (m, 4H).

[0361] Example 13: Synthesis of N-((1s,3s)-3-(6-(4-(4-((1-(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)-4-methoxybenzoyl)piperidine-4-yl)methyl)piperazine-1-yl)phenylamino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide (Compound 186)

[0362] [ka]

[0363] Except for using intermediate C-6 (10 mg, 0.0162 mmol) and 3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)-4-methoxybenzoic acid (CRBN binder 8, 5.2 mg, 0.0194 mmol), the reaction was carried out in the same manner as in step 3 of Example 1, followed by separation and purification to obtain the target compound 186 (9 mg, 69%) as a white solid.

[0364] 1H NMR (500 MHz, DMSO-d6) δ 10.37 (s, 1H), 9.86 (s, 2H), 8.56 - 8.40 (m, 2H), 8.35 (s, 0.5H), 8.23 ​​(d, J = 2.5 Hz, 0.5H), 7.78 (d, J = 8.5 Hz, 1H), 7.43 - 7.15 (m, 8H), 7.02 (d, J = 8.6 Hz, 1H), 4.85 - 4.68 (m, 1H), 4.4 (m,1H), 4.16 (m, 1H), 3.86 (s, 3H), 3.76 (d, J = 10.9 Hz, 2H), 3.61 (t, J = 6.8 Hz, 4H), 3.15 (m, 7H), 2.93 - 2.81 (m, 2H), 2.73 - 2.60 (m, 5H), 2.18 (m, 1H), 1.88 (m, 3H), 1.23 (m, 4H).

[0365] Compounds 187-479 were synthesized using the same method as compound 186, with the corresponding starting materials and CRBN binders, respectively.

[0366] Experimental Example 1: Identification of Compounds To identify the 479 compounds synthesized by the above-described series of examples, they were analyzed using a mass spectrometer and / or an NMR spectrometer, and the results are summarized in Figures 3 to 13 below.

[0367] Experimental Example 2: Evaluation of CDK proteolytic activity To evaluate the CDK protein degradation activity of the compound according to the present invention, the following experiment was conducted.

[0368] MDA-MB-231 cells were placed in 5 × 10⁶ well plates. 5Cells were injected one by one into each well. The following day, each well was treated with the compound to final concentrations of 100 nM, 1 μM, and 10 μM. The well used as the control group was treated with the same amount of DMSO as the compound. After 16 hours of treatment, the cells were collected and cell lysates were prepared using Triton X-100 lysis buffer (50 mM HEPES, pH 7.5, 40 mM NaCl, 1% Triton X-100, 1 mM EDTA, 1 mM EGTA, 10 mM pyrophosphate, 10 mM β-glycerophosphate, 50 mM NaF, 1 mM NaVO4, protease inhibitor). After quantification, the cell lysates were separated by size using polyacrylamide gel electrophoresis (SDS-PAGE). Western blots were then performed using antibodies that recognize CDK2, CDK9, and tubulin, respectively. The results obtained by Western blotting were quantitatively analyzed using the ImageJ program, and a representative image of the experimental results is shown in Figure 1. In addition, the residue rates calculated based on the enzyme resolution of CDK2 and CDK9 are shown in Table 15 below.

[0369] [Table 15-1]

[0370] [Table 15-2]

[0371] [Table 15-3]

[0372] [Table 15-4]

[0373] [Table 15-5]

[0374] Table 15-6

[0375] Table 15-7

[0376] Table 15-8

[0377] Table 15-9

[0378] Table 15-10

[0379] Table 15-11

[0380] Table 15-12

[0381] Table 15-13

[0382] Table 15-14

[0383] Table 15-15

[0384]

Table 15-16

[0385]

Table 15-17

[0386]

Table 15-18

[0387] Experimental Example 3: Evaluation of Cytotoxicity To evaluate the cytotoxicity of the compounds according to the present invention, an experiment was conducted as follows.

[0388] MDA-MB-231 cells were seeded at 3×10 3 cells per well in a 96-well plate. On the next day, each well was treated with the compound to final concentrations of 3 nM, 10 nM, 30 nM, 100 nM, 300 nM, 1 μM, 3 μM, and 10 μM. The wells used as the control group were treated with the same amount of DMSO as the compound. 72 hours after compound treatment, the number of surviving cells was analyzed using the CellTiter-Glo Luminescent Cell Viability Assay (Promega). Luminescence was measured using a VICTOR X3 Multilabel Plate Reader (PerkinElmer). The GI of the compound 50 was calculated using GraphPad Prism 5.01 software, and the result image of a representative experiment is presented in Figure 2.

[0389] Experimental Example 4: Evaluation of CDK Protein Inhibition To evaluate the inhibition of CDK2 and CDK9 protein activity by the compounds according to the present invention, experiments were conducted using KINOMEscan Technology provided by Eurofins, and the results for some selected compounds are shown in Tables 16 and 17 below.

[0390] [Table 16-1]

[0391] [Table 16-2]

[0392] [Table 17]

[0393] As can be seen from the table above, most of the compounds of the present invention exhibit high degradation activity against CDK2 and / or CDK9. In particular, some compounds showed relatively much higher degradation activity. This suggests that pharmaceutical compositions targeting CDK2 and / or CDK9-mediated diseases containing the compounds of the examples of the present invention as active ingredients may be provided.

[0394] From the above description, those skilled in the art will understand that the present invention can be implemented in other specific forms without altering its technical idea or essential features. In this regard, it should be understood that the embodiments described above are merely illustrative and not limiting. The scope of the present invention should be interpreted as encompassing all modified or altered forms derived from the meaning and scope of the claims, which will be described later, and their equivalent concepts, rather than from the above detailed description.

Claims

1. Compound of the chemical formula 1 below: 【Chemistry 1】 In the aforementioned chemical formula 1, R １ is C １－１０ alkyl, C6-10 aryl, -C １－３ alkyl-C ６－１０ aryl, 5-10 membered heteroaryl (wherein said heteroaryl contains one nitrogen atom), -C １－３ alkyl-5-10 membered heteroaryl (wherein said heteroaryl contains one nitrogen atom), C ３－１０ cycloalkyl, -C １－３ alkyl-C ３－１０ cycloalkyl, 3-10 membered heterocycloalkyl (wherein said heterocycloalkyl contains one nitrogen atom), or -C １－３ alkyl-3-10 membered heterocycloalkyl (wherein said heterocycloalkyl contains one nitrogen atom), wherein C6-10 aryl, 5-10 membered heteroaryl (wherein said heteroaryl contains one nitrogen atom), C3-10 cycloalkyl, or 3-10 membered heterocycloalkyl (wherein said heterocycloalkyl contains one nitrogen atom) is unsubstituted, or substituted with one or more groups selected from the group consisting of halogen, cyano, tert-butoxycarbonyl (-Boc), amino, nitro, hydroxy, C １－６ alkyl, halo-C １－６ alkyl, -OR ａ , -C(=O)R ａ , -C(=O)OR ａ , -C(O)NR ａ R ｂ , -SO ２ R ａ , -S(O)R ａ , -SO(N)R ａ , C １－２ alkyl-C ６－１０ aryl and C ６－１０ aryl, wherein R ａ and R ｂ are the same or different, and each independently is hydrogen, halogen, amino, C １－６ alkyl, halo-C １－６ alkyl, C ６－１０ aryl, 5-10 membered heteroaryl (wherein said heteroaryl contains one nitrogen atom), C ３－１０ It is a cycloalkyl or a 3-10 membered heterocycloalkyl (where the heterocycloalkyl contains one nitrogen atom), A is a moiety that acts as an exit vector. L stands for linker. ELB is an E3 ubiquitin ligase binder. Here, The above-mentioned A has the structure of the following chemical formula 3: 【Chemistry 2】 In the aforementioned chemical formula 3, Cy 1 is an unsubstituted or C1-3 alkyl-substituted C6-10 aryl or 5-10 membered heteroaryl (where the heteroaryl contains one or two nitrogen atoms), Cy2 is a 3-10 membered heterocycloalkyl (where the heterocycloalkyl contains one or two nitrogen atoms), l is an integer from 0 to 4, m, n, and p are mutually independent of each other and can be either 0 or 1, except when all are 0. The linker is -L1-L2-, L2 is directly connected. 【Transformation 3】 And, L1 is 【Chemistry 4】 or 【Transformation 5】 And, Here, q, t, v, x, and z are mutually independent of each other and are either 0 or 1. r, s, u, and y are independent integers between 0 and 6. Ch is a C1-4 alkenyl or C1-4 alkynyl, Cy3 and Cy4 are not present independently of each other, and are 3-10 membered heterocycloalkyls (where the heterocycloalkyl contains one or two nitrogen atoms) or C3-10 cycloalkyls, and The aforementioned ELB has the structure of the following chemical formula 2: 【Transformation 6】 In the aforementioned chemical formula 2, Cy is a C6-10 aryl, a 5-10 membered heteroaryl (where the heteroaryl contains one oxygen atom or one or three nitrogen atoms) or a 5-10 membered heterocycloalkyl (where the heterocycloalkyl contains one oxygen atom or one or three nitrogen atoms); k is between 0 and 2; X is either N or C; R2 is non-existent, hydrogen, deuterium (D), or C1-C3 alkyl; The aryl, heteroaryl, or heterocycloalkyl group is either unsubstituted or substituted with one or more selected from the group consisting of oxo, halogen, nitro, amino, hydroxy, carboxy, C1-6 alkyl, or C1-6 alkoxy groups.

2. The compound according to claim 1, wherein the chemical formula 2 is one of the following structures: 【Transformation 7】 (R ３ is hydrogen or halogen, X ２ (It is CH or N).

3. The compound according to claim 1, wherein the chemical formula 2 is one of the following structures: 【Transformation 8】 。

4. The aforementioned R １ C １－６ Alkyl, -C １－３ Alkyl-phenyl, phenyl, -C １－３ Alkyl-pyridyl, or pyridyl, where phenyl or pyridyl is unsubstituted, or C １－３ Alkyl, halogen, cyano, and halo-C １－３ The compound according to claim 1, substituted with one or more substituents selected from the group consisting of alkyl groups.

5. The aforementioned R １ The compound according to claim 1, wherein the compound is one of the following structures: 【Chemistry 9】

6. The compound according to claim 1, wherein A is one of the following structures: 【Chemistry 10】 。

7. The compound according to claim 1, wherein L1 is one of the following structures: 【Chemistry 11】

8. The aforementioned compound, N-((1s,3s)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)amino)acetamide)hexanoyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)acetamide)hexanoyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetamide)hexanoyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetamide)hexanoyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)amino)hexanoyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)hexanoyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetamide)ethoxy)ethoxy)acetyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetamide)ethoxy)ethoxy)acetyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)amino)acetamide)ethoxy)ethoxy)acetyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)acetamide)ethoxy)ethoxy)acetyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)amino)ethoxy)ethoxy)acetyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)ethoxy)ethoxy)acetyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)amino)acetamide)hexyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)acetamide)hexyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetamide)hexyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetamide)hexyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)amino)hexyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)hexyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)amino)acetamide)ethoxy)ethoxy)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)acetamide)ethoxy)ethoxy)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetamide)ethoxy)ethoxy)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetamide)ethoxy)ethoxy)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)amino)ethoxy)ethoxy)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)ethoxy)ethoxy)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)methyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)methyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperidine-4-yl)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-(2-(2,4-dioxocyclohexyl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(3-(4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperazine-1-yl)propyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(3-(4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperazine-1-yl)propyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(3-(4-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperazine-1-yl)propyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(3-(4-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperazine-1-yl)propyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(3-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)propyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(3-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperazine-1-yl)propyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)oxy)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperidine-4-yl)oxy)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)oxy)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)oxy)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)oxy)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)oxy)ethyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)acetyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperidine-4-yl)acetyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)acetyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)acetyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)acetyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)acetyl)piperidine-4-yl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(6-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)amino)acetamide)hexanoyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(6-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)acetamide)hexanoyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(6-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetamide)hexanoyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(6-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetamide)hexanoyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(6-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)amino)hexanoyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(6-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)hexanoyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetamide)ethoxy)ethoxy)acetyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetamide)ethoxy)ethoxy)acetyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)amino)acetamide)ethoxy)ethoxy)acetyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)acetamide)ethoxy)ethoxy)acetyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)ethoxy)ethoxy)acetyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)oxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetamide)ethoxy)ethoxy)ethyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)acetamide)ethoxy)ethoxy)ethyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetamide)ethoxy)ethoxy)ethyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)amino)acetamide)ethoxy)ethoxy)ethyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)methoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperidine-4-yl)methoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)methoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)methoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(3-(4-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperazine-1-yl)propoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(3-(4-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperazine-1-yl)propoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(3-(4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperazine-1-yl)propoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(3-(4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperazine-1-yl)propoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(3-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)propoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(3-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperazine-1-yl)propoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)methoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)oxy)acetyl)piperidine-4-yl)methoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)methoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)methoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(3-(4-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperazine-1-yl)propoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(3-(4-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperazine-1-yl)propoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(3-(4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperazine-1-yl)propoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(3-(4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperazine-1-yl)propoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(3-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)propoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(3-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperazine-1-yl)propoxy)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)methyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)methyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-((3-(4-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperazine-1-yl)propyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-((3-(4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperazine-1-yl)propyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-((3-(4-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperazine-1-yl)propyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-((3-(4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperazine-1-yl)propyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-((3-(4-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)propyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-((3-(4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methyl)piperazine-1-yl)propyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-((3-(4-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)propyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-((3-(4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)methyl)piperazine-1-yl)propyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)methyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)methyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide, N-((1s,3s)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)oxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide, N-((1s,3s)-3-(6-(((1-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide, N-((1s,3s)-3-(6-(((1-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)glycyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide, N-((1s,3s)-3-(6-(((1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide, N-((1s,3s)-3-(6-(((1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)glycyl)piperidine-4-yl)methyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)methyl)piperazine-1-yl)benzyl)amino)-9H-purine-9-yl)cyclobutyl)acetamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-((2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Oxy)Acetyl)Piperidin-4-yl)Methyl)Piperazine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-((2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindoline-4-yl)Oxy)Acetyl)Piperidin-4-yl)Methyl)Piperazine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Glycyl)Piperidine-4-yl)Methyl)Piperazine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-4-yl)Glycyl)Piperidine-4-yl)Methyl)Piperazine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Piperidin-4-yl)Methyl)Piperazine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-4-yl)Piperidin-4-yl)Methyl)Piperazine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-(((1-((1-(2-((2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-4-yl)Oxy)Acetyl)Piperidin-4-yl)Methyl)Piperidin-4-yl)Methyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-(((1-((1-(2-((2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Oxy)Acetyl)Piperidin-4-yl)Methyl)Piperidin-4-yl)Methyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-(((1-((1-((2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-4-yl)Glycyl)Piperidin-4-yl)Methyl)Piperidin-4-yl)Methyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-(((1-((1-((2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Glycyl)Piperidin-4-yl)Methyl)Piperidin-4-yl)Methyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-(((1-((1-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-4-yl)Piperidin-4-yl)Methyl)Piperidin-4-yl)Methyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-(((1-((1-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Piperidin-4-yl)Methyl)Piperidin-4-yl)Methyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)oxy)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-5-yl)oxy)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)glycyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-(((1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-(((1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)oxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-(((1-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-(((1-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)-4-methoxybenzoyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)benzofuran-6-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(3-((1-(2,6-dioxopiperidine-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-yl)amino)phenyl)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(1-(2,6-dioxopiperidine-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)-4-methoxybenzoyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)benzofuran-6-carbonyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(3-((1-(2,6-dioxopiperidine-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-yl)amino)phenyl)acetyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(1-(2,6-dioxopiperidine-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-yl)piperidine-4-carbonyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)-4-methoxybenzoyl)piperidine-4-yl)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)benzofuran-6-carbonyl)piperidine-4-yl)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(3-((1-(2,6-dioxopiperidine-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-yl)amino)phenyl)acetyl)piperidine-4-yl)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(1-(2,6-dioxopiperidine-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-yl)piperidine-4-carbonyl)piperidine-4-yl)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, 3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)-4-methoxy-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)methyl)cyclohexyl)methyl)benzamide, 3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)methyl)cyclohexyl)methyl)benzofuran-6-carboxamide, 2-(3-((1-(2,6-dioxopiperidine-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-yl)amino)phenyl)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)methyl)cyclohexyl)methyl)acetamide, 1-(1-(2,6-dioxopiperidine-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-yl)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)methyl)cyclohexyl)methyl)piperidine-4-carboxamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)glycyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)oxy)acetyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-5-yl)glycyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-5-yl)oxy)acetyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)glycyl)piperidine-4-yl)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)oxy)acetyl)piperidine-4-yl)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-5-yl)oxy)acetyl)piperidine-4-yl)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, 2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)methyl)cyclohexyl)methyl)acetamide, 2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)methyl)cyclohexyl)methyl)acetamide, 2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)methyl)cyclohexyl)methyl)acetamide, 2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)amino)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)methyl)cyclohexyl)methyl)acetamide, 2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-5-yl)oxy)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)methyl)cyclohexyl)methyl)acetamide, N-((1s,3s)-3-(6-((4-(4-(((1r,4r)-4-(((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)amino)methyl)cyclohexyl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, 2-(3-(2,6-dioxopiperidine-3-yl)phenoxy)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamide)cyclobutyl)-9H-purine-6-yl)amino)phenyl)piperazine-1-yl)methyl)cyclohexyl)methyl)acetamide, N-((1s,3s)-3-(6-((3-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)methyl)piperazine-1-yl)propyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(3-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(3-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(3-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((3-(4-((1-(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)-4-methoxybenzoyl)piperidine-4-yl)methyl)piperazine-1-yl)propyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((1-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)propyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((1-(2-(3-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)propyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperazine-1-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperazine-1-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperazine-1-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperazine-1-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)-4-methoxybenzoyl)piperazine-1-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperazine-1-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-(3-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperazine-1-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperazine-1-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)acetyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(((1r,4r)-4-(((2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)amino)methyl)cyclohexyl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)oxy)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)oxy)acetyl)piperidine-4-yl)oxy)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-5-yl)oxy)acetyl)piperidine-4-yl)oxy)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)oxy)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)-4-methoxybenzoyl)piperidine-4-yl)oxy)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)oxy)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-(2-(3-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)oxy)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)oxy)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)oxy)acetyl)piperidine-4-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)oxy)acetyl)piperidine-4-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)-4-methoxybenzoyl)piperidine-4-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(2-(3-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)oxy)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(6-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)-6-azaspiro[3.4]octan-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(6-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)oxy)acetyl)-6-azaspiro[3.4]octan-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(6-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)-6-azaspiro[3.4]octan-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(6-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-5-yl)oxy)acetyl)-6-azaspiro[3.4]octan-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(6-(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)-4-methoxybenzoyl)-6-azaspiro[3,4]octan-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(6-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)-6-azaspiro[3.4]octan-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(6-(2-(3-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)-6-azaspiro[3.4]octan-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)azetidine-3-yl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-yl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)-4-methoxybenzoyl)azetidine-3-yl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)azetidine-3-yl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(3-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)azetidine-3-yl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-((1-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)azetidine-3-yl)methyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-((1-(2-(3-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)azetidine-3-yl)methyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)glycyl)azetidine-3-yl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-5-yl)glycyl)azetidine-3-yl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)azetidine-3-yl)methyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-((1-(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)-4-methoxybenzoyl)azetidine-3-yl)methyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-(2-(3-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)-4-methoxybenzoyl)piperidine-4-yl)methyl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)-7-azaspiro[3.5]nonane-2-yl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-(2-(3-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)-7-azaspiro[3.5]nonane-2-yl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)-4-methoxybenzoyl)-7-azaspiro[3.5]nonane-2-yl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)oxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methyl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-(2-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-5-yl)oxy)acetyl)piperidine-4-yl)methyl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)glycyl)piperidine-4-yl)methyl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)methyl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)oxy)acetyl)-7-azaspiro[3.5]nonane-2-yl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)glycyl)-7-azaspiro[3.5]nonane-2-yl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-5-yl)oxy)acetyl)-7-azaspiro[3.5]nonane-2-yl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-5-yl)glycyl)-7-azaspiro[3.5]nonane-2-yl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)-7-azaspiro[3.5]nonane-2-yl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)-7-azaspiro[3.5]nonane-2-yl)piperidine-4-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-Dioxopiperidine-3-yl)-6-Fluoro-1,3-Dioxoisoindorin-5-yl)Piperidin-4-yl)Methyl)Piperazine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((4-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Piperadin-1-yl)Methyl)Piperadin-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((4-(2-(2,6-Dioxopiperidine-3-yl)-6-Fluoro-1,3-Dioxoisoindorin-5-yl)Piperadin-1-yl)Methyl)Piperadin-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-5-yl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((4-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-4-yl)Piperadin-1-yl)Methyl)Piperadin-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-(3-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)amino)propanoyl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((4-((2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-4-yl)Glycyl)Piperazine-1-yl)Methyl)Piperidine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((4-((2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Glycyl)Piperazine-1-yl)Methyl)Piperidine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-(7-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)-7-Azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-(7-(2-(2,6-Dioxopiperidine-3-yl)-6-Fluoro-1,3-Dioxoisoindorin-5-yl)-7-Azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-(7-(3-(2,6-Dioxopiperidine-3-yl)-4-Oxo-3,4-Dihydrobenzo[d][1,2,3]triazine-6-yl)-7-Azaspiro[3.5]nonane-2-yl)Piperadin-1-yl)Phenyl)amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-(7-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-5-yl)glycyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((4-(4-((4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)methyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-((4-((4-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperazine-1-yl)methyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-((4-((3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-5-yl)piperazine-1-yl)methyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((4-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)glycyl)piperazine-1-yl)methyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((4-(2-((2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindoline-5-yl)Oxy)Acetyl)Piperazine-1-yl)Methyl)Piperidine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, N-((1s,3s)-3-(6-((4-(4-((4-(2-((2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)oxy)acetyl)piperazine-1-yl)methyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((4-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperazine-1-yl)methyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperidine-4-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(2-(4-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)-7-azaspiro[3.5]nonane-7-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(2-(4-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)-7-azaspiro[3.5]nonane-7-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(2-(4-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperazine-1-yl)-7-azaspiro[3.5]nonane-7-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(4-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)ethyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(4-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)ethyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(4-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperazine-1-yl)ethyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(((4-((2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)methyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperidine-4-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)azetidine-3-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)azetidine-3-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)propyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)propyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(4-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperazine-1-yl)propyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)azetidine-3-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperidine-4-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(4-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperazine-1-yl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(3-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)azetidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(3-(4-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)azetidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(2-(4-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperazine-1-yl)-7-azaspiro[3.5]nonane-7-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(2-(4-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperazine-1-yl)-7-azaspiro[3.5]nonane-7-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(4-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperazine-1-yl)ethyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(4-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperazine-1-yl)ethyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(4-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperazine-1-yl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(4-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperazine-1-yl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperazine-1-yl)propyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperazine-1-yl)propyl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(3-(4-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperazine-1-yl)azetidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(4-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)piperidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-((4-((3-(2,6-Dioxopiperidine-3-yl)-4-Oxo-3,4-Dihydrobenzo[d][1,2,3]triazine-6-yl)piperazine-1-yl)Methyl)piperidine-1-yl)Phenyl)amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-Dioxopiperidine-3-yl)-4-Oxo-3,4-Dihydrobenzo[d][1,2,3]triazine-6-yl)piperidine-4-yl)Methyl)piperazine-1-yl)Phenyl)amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperidine-4-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(3-(4-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperazine-1-yl)azetidine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-yl)methyl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Piperidin-4-carbonyl)-7-Azaspiro[3.5]nonane-2-yl)Piperazine-1-yl)Phenyl)amino)-9H-Purine-9-yl)Cyclobutyl)Benzamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Azetidine-3-carbonyl)-7-Azaspiro[3.5]nonane-2-yl)Piperazine-1-yl)Phenyl)amino)-9H-Purine-9-yl)Cyclobutyl)Benzamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(7-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-fluoropicolinamide, 6-Chloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide, 6-Cyano-N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Azetidine-3-carbonyl)Piperidin-4-yl)Methyl)Piperazine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Piperidin-4-carbonyl)Piperidin-4-yl)Methyl)Piperazine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Piperidin-4-yl)Methyl)Piperidin-4-yl)Ethyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-Dioxopiperidine-3-yl)-6-Fluoro-1,3-Dioxoisoindorin-5-yl)Piperidin-4-yl)Methyl)Piperidin-4-yl)Ethyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((2-(1-((1-(3-(2,6-Dioxopiperidine-3-yl)-4-Oxo-3,4-Dihydrobenzo[d][1,2,3]triazine-6-yl)piperidine-4-yl)Methyl)piperidine-4-yl)Ethyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((2-(1-((1-(1-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Azetidine-3-carbonyl)Piperidin-4-yl)Methyl)Piperidin-4-yl)Ethyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((2-(1-((1-(1-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Piperidin-4-carbonyl)Piperidin-4-yl)Methyl)Piperidin-4-yl)Ethyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-yl)methyl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Piperidin-4-yl)Ethyl)Piperazine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-Dioxopiperidine-3-yl)-6-Fluoro-1,3-Dioxoisoindorin-5-yl)Piperidin-4-yl)Ethyl)Piperazine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-(2-(1-(3-(2,6-Dioxopiperidine-3-yl)-4-Oxo-3,4-Dihydrobenzo[d][1,2,3]triazine-6-yl)piperidine-4-yl)Ethyl)Piperazine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, N-((1s,3s)-3-(6-((4-(4-(1-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)butyl)piperidine-4-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Azetidine-3-carbonyl)Piperidin-4-yl)Ethyl)Piperazine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Piperidin-4-carbonyl)Piperidin-4-yl)Ethyl)Piperazine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 6-Cyano-N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, 6-Chloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide, 6-Chloro-N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide, 6-Cyano-N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide, 6-Chloro-N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide, 6-Cyano-N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-(3-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)propyl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)propyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindoline-4-yl)butyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-fluoropicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-fluoropicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)glycyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-fluoropicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)propyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-fluoropicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-4-yl)butyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-fluoropicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(4-(2,6-Dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-(4-(2,6-Dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, 6-Chloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide, 6-Cyano-N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-1-oxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-(7-(2-(4-(2,6-Dioxopiperidine-3-yl)phenoxy)acetyl)-7-Azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(4-(2,6-dioxopiperidine-3-yl)phenoxy)acetyl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)-2-methylphenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)methyl)piperazine-1-yl)-2-methylphenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)-2-methylphenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)-2-methylphenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, 6-Chloro-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide, 6-Chloro-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide, 6-Chloro-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide, 6-Cyano-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide, 6-Cyano-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)ethyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)propyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperidine-4-yl)ethyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-Dioxopiperidine-3-yl)-6-Fluoro-1,3-Dioxoisoindorin-5-yl)Piperidin-4-Carbonyl)Piperidin-4-yl)Methyl)Piperazine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(2-(2,6-Dioxopiperidine-3-yl)-6-Fluoro-1,3-Dioxoisoindorin-5-yl)Piperidin-4-Carbonyl)Piperidin-4-yl)Ethyl)Piperazine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-fluoropicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-fluoropicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-fluoropicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)azetidine-3-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, 6-Cyano-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)picolinamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-((4-((4-(1-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Azetidine-3-carbonyl)Piperazine-1-yl)Methyl)Piperidine-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-((4-((4-(1-(2-(2,6-Dioxopiperidine-3-yl)-1,3-Dioxoisoindorin-5-yl)Piperidin-4-carbonyl)Piperazine-1-yl)Methyl)Piperidin-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, 2,6-Dichloro-N-((1s,3s)-3-(6-((4-((4-((4-(1-(2-(2,6-Dioxopiperidine-3-yl)-6-Fluoro-1,3-Dioxoisoindorin-5-yl)Piperidin-4-Carbonyl)Piperazine-1-yl)Methyl)Piperidin-1-yl)Phenyl)Amino)-9H-Purin-9-yl)Cyclobutyl)Benzamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidine-3-yl)-6-fluoro-1,3-dioxoisoindorin-5-yl)piperidine-4-carbonyl)piperidine-4-yl)methyl)piperazine-1-yl)-2-methylphenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidine-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazine-6-yl)piperidine-4-yl)methyl)piperazine-1-yl)-2-methylphenyl)amino)-9H-purine-9-yl)cyclobutyl)-6-methylpicolinamide, or N-((1s,3s)-3-(6-((4-(4-(7-(4-(4-(2-(2,6-dioxopiperidine-3-yl)-1,3-dioxoisoindorin-5-yl)piperazine-1-yl)buto-2-in-1-yl)-7-azaspiro[3.5]nonane-2-yl)piperazine-1-yl)phenyl)amino)-9H-purine-9-yl)cyclobutyl)-2-phenylacetamide The compound according to claim 1.

9. The first step involves reacting the compound of chemical formula 4 with a derivative of A moiety containing an amine group at one end and a protecting group at the other, and deprotecting it to prepare the compound of chemical formula 5; The compound of chemical formula 5 has a reactive functional group X at one end. ２ The second step involves reacting the other end with a derivative of L1 moiety containing a protecting group to deprotect it and prepare the compound of chemical formula 6; and The compound of chemical formula 5 has a reactive functional group X at one end. ３ A method for producing a compound according to any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof, comprising a third step of reacting with a CRBN binder containing: 【Chemistry 12】 In the aforementioned chemical formulas 4 to 6, X １ and X ３ These are, independently of each other, halogens or hydroxyls. X ２ These are halogens, oxo, or hydroxyl compounds. The protecting group is tert-butoxycarbonyl. A' and L1' may be identical to A and L1, respectively, or in the form of salts thereof. Here, The first step is carried out by using a compound in which X1 is a halogen, reacting it in a lower alcohol solvent at a temperature of 70°C to 100°C, and then deprotecting it by treating it with a strong acid solution in an organic solvent. The second step involves reacting a compound in which X2 is hydroxyl with EDCI (1-ethyl-3-(3-dimethylaminopropyl)carbonidimide), HOBt (hydroxybenzotriazole), and DIPEA (N,N-disopropylethylamine) in an organic solvent at 15°C to 40°C, and then deprotecting the compound by treating it with a strong acid solution in an organic solvent. The third step is carried out by reacting a compound in which X3 is hydroxyl with EDCI, HOBt, and DIPEA in an organic solvent at 15°C to 40°C. The aforementioned CRBN binder is 【Chemistry 13】 It is one of the groups selected from the group consisting of, The above-mentioned A has the structure of the following chemical formula 3: 【Chemistry 14】 In the aforementioned chemical formula 3, Cy 1 is an unsubstituted or C1-3 alkyl-substituted C6-10 aryl or 5-10 membered heteroaryl (where the heteroaryl contains one nitrogen atom), Cy2 is a 3-10 membered heterocycloalkyl (where the heterocycloalkyl contains one nitrogen atom), l is an integer between 0 and 4, and m, n, and p are independently 0 or 1, except when all are 0; The aforementioned L1 is 【Chemistry 15】 or 【Chemistry 16】 And, Here, q, t, v, x, and z are mutually independent of each other and are either 0 or 1. r, s, u, and y are independent integers between 0 and 6. Ch is a C1-4 alkenyl or C1-4 alkynyl, Cy3 and Cy4 are 3-10 membered heterocycloalkyl groups (where the heterocycloalkyl group contains one nitrogen atom) or C3-10 cycloalkyl groups that do not exist independently of each other.

10. A first step of preparing a compound of chemical formula 5 by reacting the compound of chemical formula 4 below with a derivative of A moiety having an amine group at one end and a protecting group at the other end, and deprotecting it; A second step involves reacting the compound of chemical formula 5 with a derivative of L1 moiety containing a reactive functional group X2 at one end and a protecting group at the other end, thereby deprotecting and preparing the compound of chemical formula 6; and A method for producing the compound of any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof, comprising a third step of reacting the compound of chemical formula 5 with a CRBN binder having a reactive functional group X3 at one end: 【Chemistry 17】 In the aforementioned chemical formulas 4 to 6, X1 and X3 are independently halogens or hydroxyls. X2 is a halogen, oxo, or hydroxyl, The protecting group is tert-butoxycarbonyl. A' and L1' may be identical to A and L1, respectively, or in the form of salts thereof. Here, The first step is carried out by using a compound in which X1 is a halogen, reacting it in a lower alcohol solvent at a temperature of 70°C to 100°C, and then deprotecting it by treating it with a strong acid solution in an organic solvent. The second step involves reacting a compound in which X2 is hydroxyl with EDCI (1-ethyl-3-(3-dimethylaminopropyl)carbonidimide), HOBt (hydroxybenzotriazole), and DIPEA (N,N-disopropylethylamine) in an organic solvent at 15°C to 40°C, and then deprotecting the compound by treating it with a strong acid solution in an organic solvent. The third step is carried out by reacting a compound in which X3 is a halogen with DIPEA in an organic solvent at 70°C to 100°C. The aforementioned CRBN binder is [Chemistry 18] It is one of the groups selected from the group consisting of, The above-mentioned A has the structure of the following chemical formula 3: 【Chemistry 19】 In the aforementioned chemical formula 3, Cy 1 is an unsubstituted or C1-3 alkyl-substituted C6-10 aryl or 5-10 membered heteroaryl (where the heteroaryl contains one nitrogen atom), Cy2 is a 3-10 membered heterocycloalkyl (where the heterocycloalkyl contains one nitrogen atom), l is an integer between 0 and 4, and m, n, and p are independently 0 or 1, except when all are 0; The aforementioned L1 is 【Chemistry 20】 or 【Chemistry 21】 And, Here, q, t, v, x, and z are mutually independent of each other and are either 0 or 1. r, s, u, and y are independent integers between 0 and 6. Ch is a C1-4 alkenyl or C1-4 alkynyl, Cy3 and Cy4 are 3-10 membered heterocycloalkyl groups (where the heterocycloalkyl group contains one nitrogen atom) or C3-10 cycloalkyl groups that do not exist independently of each other.

11. A first step of preparing a compound of chemical formula 5 by reacting the compound of chemical formula 4 below with a derivative of A moiety having an amine group at one end and a protecting group at the other end, and deprotecting it; A second step involves reacting the compound of chemical formula 5 with a derivative of L1 moiety containing a reactive functional group X2 at one end and a protecting group at the other end, thereby deprotecting and preparing the compound of chemical formula 6; and A method for producing the compound of any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof, comprising a third step of reacting the compound of chemical formula 5 with a CRBN binder having a reactive functional group X3 at one end: 【Chemistry 22】 In the aforementioned chemical formulas 4 to 6, X1 and X3 are independently halogens or hydroxyls. X2 is a halogen, oxo, or hydroxyl, The protecting group is tert-butoxycarbonyl. A' and L1' may be identical to A and L1, respectively, or in the form of salts thereof. Here, The first step is carried out by using a compound in which X1 is a halogen, reacting it in a lower alcohol solvent at a temperature of 70°C to 100°C, and then deprotecting it by treating it with a strong acid solution in an organic solvent. The second step is carried out by reacting a compound in which X2 is a halogen under basic conditions in an organic solvent at 40°C to 80°C, and then treating it with a strong acid solution in the organic solvent to deprotect it. The third step is carried out by reacting a compound in which X3 is hydroxyl with EDCI, HOBt, and DIPEA in an organic solvent at 15°C to 40°C. The aforementioned CRBN binder is 【Chemistry 23】 It is one of the groups selected from the group consisting of, The above-mentioned A has the structure of the following chemical formula 3: 【Chemistry 24】 In the aforementioned chemical formula 3, Cy 1 is an unsubstituted or C1-3 alkyl-substituted C6-10 aryl or 5-10 membered heteroaryl (where the heteroaryl contains one nitrogen atom), Cy2 is a 3-10 membered heterocycloalkyl (where the heterocycloalkyl contains one nitrogen atom), l is an integer between 0 and 4, and m, n, and p are independently 0 or 1, except when all are 0; The aforementioned L1 is 【Chemistry 25】 or 【Chemistry 26】 And, Here, q, t, v, x, and z are mutually independent of each other and are either 0 or 1. r, s, u, and y are independent integers between 0 and 6. Ch is a C1-4 alkenyl or C1-4 alkynyl, Cy3 and Cy4 are 3-10 membered heterocycloalkyl groups (where the heterocycloalkyl group contains one nitrogen atom) or C3-10 cycloalkyl groups that do not exist independently of each other.

12. A first step of preparing a compound of chemical formula 5 by reacting the compound of chemical formula 4 below with a derivative of A moiety having an amine group at one end and a protecting group at the other end, and deprotecting it; A second step involves reacting the compound of chemical formula 5 with a derivative of L1 moiety containing a reactive functional group X2 at one end and a protecting group at the other end, thereby deprotecting and preparing the compound of chemical formula 6; and A method for producing the compound of any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof, comprising a third step of reacting the compound of chemical formula 5 with a CRBN binder having a reactive functional group X3 at one end: 【Chemistry 27】 In the aforementioned chemical formulas 4 to 6, X1 and X3 are independently halogens or hydroxyls. X2 is a halogen, oxo, or hydroxyl, The protecting group is tert-butoxycarbonyl. A' and L1' may be identical to A and L1, respectively, or in the form of salts thereof. Here, The first step is carried out by using a compound in which X1 is a halogen, reacting it in a lower alcohol solvent at a temperature of 70°C to 100°C, and then deprotecting it by treating it with a strong acid solution in an organic solvent. The second step is carried out by reacting a compound in which X2 is a halogen under basic conditions in an organic solvent at 40°C to 80°C, and then treating it with a strong acid solution in an organic solvent to deprotect it. The third step is carried out by reacting a compound in which X3 is a halogen with DIPEA in an organic solvent at 70°C to 100°C. The aforementioned CRBN binder is 【Chemistry 28】 It is one of the groups selected from the group consisting of, The above-mentioned A has the structure of the following chemical formula 3: 【Chemistry 29】 In the aforementioned chemical formula 3, Cy 1 is an unsubstituted or C1-3 alkyl-substituted C6-10 aryl or 5-10 membered heteroaryl (where the heteroaryl contains one nitrogen atom), Cy2 is a 3-10 membered heterocycloalkyl (where the heterocycloalkyl contains one nitrogen atom), l is an integer between 0 and 4, and m, n, and p are independently 0 or 1, except when all are 0; The aforementioned L1 is 【Transformation 30】 or 【Chemistry 31】 And, Here, q, t, v, x, and z are mutually independent of each other and are either 0 or 1. r, s, u, and y are independent integers between 0 and 6. Ch is a C1-4 alkenyl or C1-4 alkynyl, Cy3 and Cy4 are 3-10 membered heterocycloalkyl groups (where the heterocycloalkyl group contains one nitrogen atom) or C3-10 cycloalkyl groups that do not exist independently of each other.

13. A first step of preparing a compound of chemical formula 5 by reacting the compound of chemical formula 4 below with a derivative of A moiety having an amine group at one end and a protecting group at the other end, and deprotecting it; A second step involves reacting the compound of chemical formula 5 with a derivative of L1 moiety containing a reactive functional group X2 at one end and a protecting group at the other end, thereby deprotecting and preparing the compound of chemical formula 6; and A method for producing the compound of any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof, comprising a third step of reacting the compound of chemical formula 5 with a CRBN binder having a reactive functional group X3 at one end: 【Chemistry 32】 In the aforementioned chemical formulas 4 to 6, X1 and X3 are independently halogens or hydroxyls. X2 is a halogen, oxo, or hydroxyl, The protecting group is tert-butoxycarbonyl. A' and L1' may be identical to A and L1, respectively, or in the form of salts thereof. Here, The first step is carried out by using a compound in which X1 is a halogen, reacting it in a lower alcohol solvent at a temperature of 70°C to 100°C, and then deprotecting it by treating it with a strong acid solution in an organic solvent. The second step is to use a compound in which X2 is an oxo, i) React DIPEA with sodium triacetoxyborohydride (NaBH(OAc)3) at 15°C to 40°C, or ii) React sodium borohydride (NaBH3CN) with acetic acid in a lower alcohol solvent at 15°C to 40°C. This is done by treating the area with a strong acid solution in an organic solvent to deprotect it. The third step is carried out by reacting a compound in which X3 is hydroxyl with EDCI, HOBt, and DIPEA in an organic solvent at 15°C to 40°C. The aforementioned CRBN binder is 【Transformation 33】 It is one of the groups selected from the group consisting of, The above-mentioned A has the structure of the following chemical formula 3: 【Transformation 34】 In the aforementioned chemical formula 3, Cy 1 is an unsubstituted or C1-3 alkyl-substituted C6-10 aryl or 5-10 membered heteroaryl (where the heteroaryl contains one nitrogen atom), Cy2 is a 3-10 membered heterocycloalkyl (where the heterocycloalkyl contains one nitrogen atom), l is an integer between 0 and 4, and m, n, and p are independently 0 or 1, except when all are 0; The aforementioned L1 is 【Chemistry 35】 or 【Transformation 36】 And, Here, q, t, v, x, and z are mutually independent of each other and are either 0 or 1. r, s, u, and y are independent integers between 0 and 6. Ch is a C1-4 alkenyl or C1-4 alkynyl, Cy3 and Cy4 are 3-10 membered heterocycloalkyl groups (where the heterocycloalkyl group contains one nitrogen atom) or C3-10 cycloalkyl groups that do not exist independently of each other.

14. A first step of preparing a compound of chemical formula 5 by reacting the compound of chemical formula 4 below with a derivative of A moiety having an amine group at one end and a protecting group at the other end, and deprotecting it; A second step involves reacting the compound of chemical formula 5 with a derivative of L1 moiety containing a reactive functional group X2 at one end and a protecting group at the other end, thereby deprotecting and preparing the compound of chemical formula 6; and A method for producing the compound of any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof, comprising a third step of reacting the compound of chemical formula 5 with a CRBN binder having a reactive functional group X3 at one end: 【Chemistry 37】 In the aforementioned chemical formulas 4 to 6, X1 and X3 are independently halogens or hydroxyls. X2 is a halogen, oxo, or hydroxyl, The protecting group is tert-butoxycarbonyl. A' and L1' may be identical to A and L1, respectively, or in the form of salts thereof. Here, The first step is carried out by using a compound in which X1 is a halogen, reacting it in a lower alcohol solvent at a temperature of 70°C to 100°C, and then deprotecting it by treating it with a strong acid solution in an organic solvent. The second step is to use a compound in which X2 is an oxo, i) React DIPEA with sodium triacetoxyborohydride (NaBH(OAc)3) at 15°C to 40°C, or ii) React sodium borohydride (NaBH3CN) with acetic acid in a lower alcohol solvent at 15°C to 40°C. This is done by treating the area with a strong acid solution in an organic solvent to deprotect it. The third step is carried out by reacting a compound in which X3 is a halogen with DIPEA in an organic solvent at 70°C to 100°C. The aforementioned CRBN binder is 【Transformation 38】 It is one of the groups selected from the group consisting of, The above-mentioned A has the structure of the following chemical formula 3: 【Chemistry 39】 In the aforementioned chemical formula 3, Cy 1 is an unsubstituted or C1-3 alkyl-substituted C6-10 aryl or 5-10 membered heteroaryl (where the heteroaryl contains one nitrogen atom), Cy2 is a 3-10 membered heterocycloalkyl (where the heterocycloalkyl contains one nitrogen atom), l is an integer between 0 and 4, and m, n, and p are independently 0 or 1, except when all are 0; The aforementioned L1 is 【Chemistry 40】 or 【Chemistry 41】 And, Here, q, t, v, x, and z are mutually independent of each other and are either 0 or 1. r, s, u, and y are independent integers between 0 and 6. Ch is a C1-4 alkenyl or C1-4 alkynyl, Cy3 and Cy4 are 3-10 membered heterocycloalkyl groups (where the heterocycloalkyl group contains one nitrogen atom) or C3-10 cycloalkyl groups that do not exist independently of each other.

15. A composition comprising a compound according to any one of claims 1 to 8, and a pharmaceutically acceptable carrier.

16. A pharmaceutical composition for inhibiting or degrading CDK2 (cyclin-dependent kinase 2), CDK9 (cyclin-dependent kinase 9), or both, comprising a compound described in any one of claims 1 to 8 as an active ingredient.

17. A pharmaceutical composition for the prevention or treatment of cancer or human immunodeficiency virus (HIV) infection, comprising a compound according to any one of claims 1 to 8 as an active ingredient.

18. The pharmaceutical composition according to claim 17, wherein the cancer is prostate cancer, lymphoma, glioblastoma, neuroblastoma, ovarian cancer, hepatocellular carcinoma, liver cancer, breast cancer, leukemia, pancreatic cancer, colorectal cancer, lung cancer, colon cancer, or multiple myeloma.

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