Compounds for inhibiting or degrading CDK2 and / or CDK9 and their medical uses

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 the activity of inhibiting or degrading CDK2 (cyclin-dependent kinase 2) and / or CDK9 (cyclin-dependent kinase 9), as well as methods for producing the same. The present invention also relates to pharmaceutical compositions containing 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 the pharmaceutical use of the compound according to the present invention for treating or preventing a disease associated with CDK2 or CDK9. [Background technology]

[0002] CDK (cyclin-dependent kinase) is a serine / threonine protein kinase that is activated by binding to cyclin. CDK has several isoforms, and 21 CDK isoforms are expressed in humans. Each CDK plays a different role in the cell, but functionally they can be broadly divided into those involved in the cell cycle and those involved in transcription.

[0003] CDK2, one of the CDKs that regulates the cell cycle, is activated through binding with cyclin E or cyclin A. The CDK2-cyclin E complex regulates the transition to S-phase, while the CDK2-cyclin A complex regulates DNA synthesis during S-phase. Uncontrolled CDK2 activation induces cells to enter S-phase even in the absence of growth factors, which increases chromosomal instability and cell proliferation, leading to cancer development. Indeed, 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) have been reported to be overexpressed in various cancers. These research results suggest that selective degradation of CDK2 may be effective in treating cancers in which CDK2 is overexpressed. International Patent Publication WO 2006 / 040036 also discloses that CDK2 inhibitors are useful for treating breast cancer, colon cancer, lung cancer, and prostate cancer.

[0004] CDK9 is one of the CDKs that regulate transcription, and CDK9 binds to cyclin T1, cyclin T2, or cyclin K to form the P-TEFb (positive transcription elongation factor) complex, which phosphorylates RNA polymerase II and promotes 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, CDK9 suppression suppresses the proliferation of various cancer cells (prostate, pancreatic, breast, and multiple myeloma), including chronic lymphocytic leukemia (CLL) (Endocrine-Related Cancer, 2016, 23:T211-T226). Furthermore, human immunodeficiency virus (HIV) utilizes host P-TEFb for viral replication, making CDK9 a candidate target protein for suppressing HIV replication (Cancer Biol. Ther., 2002, 1:342-347). Furthermore, International Patent Publication WO 2017 / 001354 discloses that CDK9 inhibitors are useful in the treatment of cancers such as acute myeloid leukemia, multiple myeloma, chronic lymphocytic leukemia, diffuse large B-cell lymphoma, Burkitt's lymphoma, follicular lymphoma, breast cancer, lung cancer, neuroblastoma, colon cancer, etc., and also 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 targeted 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 created by linking inhibitor or binder compounds that bind to specific proteins with ligand compounds that specifically bind to E3 ubiquitin ligases using various linkers. PROTACs target and degrade only disease-causing target proteins, reducing the likelihood of drug resistance. They can achieve sufficient therapeutic effect through target protein degradation even without strong binding affinity. They can also be applied to targets that are untreatable with existing drugs, drawing attention as a novel therapeutic technology.

[0006] However, not all inhibitors (binding factors) can be bound to E3 ubiquitin ligase ligand compounds to produce effective PROTAC substances; their effectiveness varies depending on the binding moiety, 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] WO2019199816 A1 [Patent Document 5] WO2019023553 A1 [Patent Document 6] US20180125821 A1 [Patent Document 7] US20190192668 A1 [Patent Document 8] WO2017197056 A1 [Patent Document 9] WO2019186358 A1 [Patent Document 10] WO2018089736 A1 [Patent Document 11] Korean Registration Patent No. 1893879

Non-licensed literature

[0008]

Non-patent document 1

Non-patent document 2

Non-patent document 3

Non-patent document 4

Non-patented document 5

Non-patent document 6

Non-patent document 7

[0009] One object of the present invention is to provide a compound or a pharmaceutically acceptable salt thereof that has an activity of inhibiting and / or degrading CDK2 and / or CDK9.

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

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

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

[0013] It is still another object of the present invention to provide a pharmaceutical composition for preventing or treating cancer or human immunodeficiency virus (HIV) infection, which comprises the compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0014] It is still another object of the present invention to provide a method for preventing or treating cancer or human immunodeficiency virus infection, which comprises 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 exhibit various pharmacological activities by inhibiting or degrading CDK2 and / or CDK9, pharmaceutical compositions containing them as active ingredients, medical uses of these (particularly for treating or preventing cancer or human immunodeficiency virus (HIV) infection), and therapeutic methods comprising administering these to individuals in need of such 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 have high selectivity in the inhibition of CDK2 and / or CDK9 activity or degradation, and therefore can exhibit excellent medicinal effects. [Brief explanation of the drawings]

[0016] [Figure 1] FIG. 1 is a diagram illustrating the results of evaluating the CDK proteolytic activity of some compounds according to the present invention. [Figure 2] FIG. 1 is a diagram illustrating the results of evaluating the cytotoxicity of some compounds according to the present invention. [Figure 3-13] FIG. 1 is a diagram summarizing the results of analyzing 479 compounds synthesized according to the present invention using a mass spectrometer and / or an NMR spectrometer. DETAILED DESCRIPTION OF THE INVENTION

[0017] Each description and embodiment disclosed in the present invention 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, and the following specific description is not intended to limit the scope of the present invention.

[0018] Additionally, those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein and such equivalents are intended to be encompassed by the present invention.

[0019] Additionally, throughout the specification of the present invention, when a part is described as "comprising" a certain component, this does not mean that it excludes other components, but that it may further include other components, unless otherwise specified. The following description is merely illustrative and is not intended to limit the invention, application, or uses.

[0020] The present invention will now be described in more detail.

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

[0022] [ka]

[0023] In the above 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, where 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 aryl, wherein R a and R b are the same or different and independently represent hydrogen, halogen, amino, C 1-6 Alkyl, Halo-C 1-6 Alkyl, C 6-10 Aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl or 3-10 membered heterocycloalkyl; A is a moiety that acts as an exit vector, L is a linker, ELB is an E3 ubiquitin ligase binder.

[0024] For example, in Formula 1, ELB may have the structure of Formula 2:

[0025] [ka]

[0026] In the above Chemical Formula 2, Cy is C 6-10 aryl, 5-10 membered heteroaryl or 5-10 membered heterocycloalkyl; k is 0 to 2; X is N or C; R2 is absent, hydrogen, deuterium (D), or C1-C3 alkyl; The aryl, heteroaryl or heterocycloalkyl may be unsubstituted or substituted with oxo, halogen, nitro, amino, hydroxy, carboxy, C 1-6 Alkyl, or C 1-6 and substituted with one or more selected from the group consisting of alkoxy.

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

[0031] [ka] .

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

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

[0034] [ka]

[0035] For example, in Formula 1, A may have the structure of Formula 3 below, but is not limited thereto:

[0036] [ka]

[0037] In the above Chemical Formula 3, Cy1 is unsubstituted or C 1-3 Alkyl-substituted C 6-10 aryl or 5-10 membered heteroaryl, Cy2 is a 3-10 membered heterocycloalkyl; l is an integer of 0 to 4, and m, n, and p are each independently 0 or 1, excluding the case where all are 0.

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

[0039] [ka]

[0040] For example, in Chemical Formula 1, the linker can be represented by -L1-L2-.

[0041] At that time, L2 is a direct connection,

[0042] [ka]

[0043] and L1 is

[0044] [ka]

[0045] or

[0046] [ka]

[0047] may be.

[0048] wherein q, t, v, and y are each independently 0 or 1; r, s, u, and x are each independently an integer of 0 to 6; Cy3 and Cy4 are each independently absent, 3- to 10-membered heterocycloalkyl or C 3-10 It may be, but is not limited to, cycloalkyl.

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

[0050] [ka]

[0051] In one embodiment of the present invention, the ELB moiety of Chemical Formula 1 refers to an E3 ligase ligand, and after the CDK2 and / or CDK9 binder moiety of Chemical Formula 1 according to the present invention binds to CDK2 and / or CDK9, it functions to link the target protein, CDK2 and / or CDK9, to the E3 ligase (Step 1), and after ubiquitin from the E2 complexed with the E3 ligase is polyubiquitinated to lysine in the target protein (Step 2), it functions to degrade or inhibit CDK2 and / or CDK9 through a process of degradation by the proteasome (Step 3). Such degraders can be recycled in the same manner (Step 4).

[0052] In one aspect of the present invention, the linker of Formula 1 is a linker that connects a CDK2 and / or CDK9 inhibitor to an E3 ligase ligand compound, and such a linker can be connected to the CDK2 and / or CDK9 inhibitor compound through an alkyl bond via chloride, bromide, iodide, or tosylate, an amide bond via an acid, or an amide bond via an amine. Examples of such linkers include those disclosed in prior patents US20180353501 A1, WO2019199816 A1, WO2019023553 A1, US20180125821 A1, US20190192668 A1, WO2017197056 A1, WO2019186358 A1, and / or WO2018089736 A1. The contents of the above-referenced prior patent application publications are hereby incorporated by reference in their entirety.

[0053] In a typical embodiment, the linker has a chain of 2 to 14, 15, 16, 17, 18, or 20 or more carbon atoms, wherein one or more carbon atoms can be replaced by a heteroatom such as O, N, S, or P. In certain embodiments, 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 in the chain. For example, the chain can include one or more ethylene glycol units, which can be consecutive, partially consecutive, or discontinuous (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 ethylene glycol units). In certain embodiments, the chain has at least 1, 2, 3, 4, 5, 6, 7, or 8 consecutive chains, which can have branches that are independently alkyl, heteroalkyl, aryl, heteroaryl, alkenyl, or alkynyl, cycloalkyl, or heterocycloalkyl substituents.

[0054] In other embodiments, the linker can comprise or be composed of one or more ethylene glycol, propylene glycol, lactic acid, and / or glycolic acid units. Generally, propylene glycol adds hydrophobicity, while ethylene glycol adds hydrophilicity. Lactic acid segments have a longer half-life than glycolic acid segments. Block and random lactic acid-glycolic acid moieties, as well as ethylene glycol and propylene glycol, are known in the art to be pharmaceutically acceptable and can be modified or arranged to achieve the desired half-life and hydrophilicity. In certain aspects, these units can be flanked or interspersed with other moieties, including alkyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, etc., as needed to achieve appropriate drug properties.

[0055] Non-limiting examples of the compound of Formula 1 according to the present invention are disclosed in Tables 1 to 14 below, each with a name and chemical structure.

[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 according to the present disclosure, for 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 more preferred, but are not limited to these.

[0156] The compounds of the present invention may exist in the form of pharmaceutically acceptable salts. As salts, acid addition salts formed with pharmaceutically acceptable free acids are useful. The term "pharmaceutically acceptable salts" as used herein refers to any organic or inorganic addition salt of the compound represented by Chemical Formula 1 that is relatively non-toxic and harmless at concentrations that have an effective effect on patients, and the side effects caused by this salt do not reduce the beneficial effects of the compound.

[0157] Acid addition salts are prepared by conventional methods, for example, by dissolving the compound in an excess amount of aqueous acid and precipitating the salt with a water-miscible organic solvent such as methanol, ethanol, acetone, or acetonitrile. Equal molar amounts of the compound and an acid or alcohol (e.g., glycol monomethyl ether) in water are heated, and the mixture is then evaporated to dryness, or the precipitated salt can be filtered off with suction.

[0158] In this regard, the free acid may be an organic acid or an inorganic acid. Examples of inorganic acids that may be used include hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, and tartaric acid. Examples of organic acids that may be used include, but are not limited to, 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, and hydroiodic acid.

[0159] Pharmaceutically acceptable metal salts can also be prepared using bases. Alkali metal salts or alkaline earth metal salts can be obtained, for example, by dissolving a compound in an excess amount of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate. In this case, sodium, potassium, or calcium salts are particularly suitable for pharmaceutical purposes, but are not limited to these. Corresponding silver salts can also be obtained by reacting an alkali metal or alkaline earth metal salt with an appropriate 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 compounds of Formula 1. For example, pharmaceutically acceptable salts may include sodium, calcium, and potassium salts of hydroxy groups, and other pharmaceutically acceptable salts of amino groups include hydrobromide, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate, dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate), and p-toluenesulfonate (tosylate) salts, which may be prepared by salt preparation methods known in the art.

[0161] As the salt of the compound of the present invention, any pharmaceutically acceptable salt of the compound of Chemical Formula 1 that exhibits pharmacological activity equivalent to that of the compound of Chemical Formula 1 can be used without limitation.

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

[0163] Furthermore, the compound represented by Chemical Formula 1 according to the present invention may be prepared in a crystalline or amorphous form, and if prepared in a crystalline form, may be optionally hydrated or solvated. The present invention may include not only stoichiometric hydrates 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 preparing the compound of the first aspect or a pharmaceutically acceptable salt thereof, comprising: a first step of reacting a compound of formula 4 with a derivative of an A moiety having an amine group at one end and a protecting group at the other end, followed by deprotection to prepare a compound of formula 5; a second step of reacting the compound of formula 5 with a derivative of an L moiety having a reactive functional group X2 at one end and a protecting group at the other end, followed by deprotection to prepare a compound of formula 6; and a third step of reacting the compound of formula 5 with a CRBN binder having a reactive functional group X3 at one end:

[0165] [ka]

[0166] [ka]

[0167] [ka]

[0168] In the above Chemical Formulas 4 to 6, X1, X2 and X3 are independently halogen or hydroxy; The protecting group is tert-butoxycarbonyl, A' and L1' may be the same as A and L1, respectively, or may be in the form of a salt thereof.

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

[0170] in particular 、 The CRBN binder is

[0171] [ka]

[0172] It may be any one selected from the group consisting of, but is not limited to,

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

[0174] For example, the second step may be i) A compound in which X2 is hydroxy is reacted with EDCI (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide), HOBt (hydroxybenzotriazole), and DIPEA (N,N-diisopropylethylamine) in an organic solvent at 15°C to 40°C, ii) Using a compound in which X2 is halogen, reacting in an organic solvent under basic conditions at 40°C to 80°C, iii) Compounds where X2 is oxo are reacted with DIPEA and sodium triacetoxyborohydride (NaBH(OAc)3) at 15°C to 40°C; or iv) A compound in which X2 is oxo is reacted with sodium cyanoborohydride (NaBH3CN) in the presence of acetic acid in a lower alcohol solvent at 15°C to 40°C, This can be achieved by treating with a strong acid solution in an organic solvent to deprotect the compound, but is not limited thereto.

[0175] Furthermore, depending on the type of linker to be introduced, the second step may involve consecutively carrying out two or more of the same or different reactions selected from the above four reactions, but is not limited thereto.

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

[0177] As mentioned above, the reaction in each step can be carried out in a lower alcohol or organic solvent. For example, the lower alcohol solvent can be C 1-4 The alkyl alcohol may be, but is not limited to, methanol or ethanol, and the organic solvent may be, but is not limited to, dimethylformamide (DMF), dichloromethane (DCM), dimethyl sulfoxide (DMSO), etc., which may be used alone or in combination.

[0178] The strong acid solution may be a solution containing hydrochloric acid, and the basic condition may be achieved using potassium carbonate (K2CO3), but is not limited thereto.

[0179] The specific reactions for carrying out steps 1 to 3 are merely suggested as examples, and the scope of the present invention is not limited thereto, and similar reactions known in the art can be used without limitation. Furthermore, the preparation method of the present invention may further include, but is not limited to, steps of separation, purification, and / or washing after each step.

[0180] A third aspect of the present invention provides a composition comprising a 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 preventing or treating 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 aspect" and "pharmaceutically acceptable salt" of the present invention are as defined above.

[0184] In specific examples of the present invention, it was confirmed that the compounds of the present invention exhibited the effect of degrading or inhibiting the activity of CDK2, CDK9, or both, suggesting that compositions containing the compounds of the present invention can efficiently inhibit or degrade CDK2, CDK9, or both, and further suggesting that they can be useful in the prevention or treatment of diseases induced by these enzymes.

[0185] As used herein, the term "prevention" refers to any action that inhibits or delays the occurrence, spread, and recurrence of cancer or viral infection diseases by administering the composition of the present invention, and "treatment" refers to any action that improves or beneficially alters the symptoms of the 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 cancer diseases or human immunodeficiency virus infection diseases, and examples of the cancer diseases include pseudomyxoma, intrahepatic bile duct cancer, hepatoblastoma, liver cancer, thyroid cancer, colon cancer, testicular cancer, myelodysplastic syndrome, glioblastoma, oral cancer, lip cancer, mycosis fungoides, acute myeloid leukemia, acute lymphocytic leukemia, basal cell carcinoma, ovarian epithelial cancer, ovarian germ cell cancer, 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 of Vater cancer, bladder cancer, peritoneal cancer, parathyroid cancer, adrenal cancer, nasal and paranasal sinus cancer, non-small cell lung cancer, non-Hodgkin's lymphoma, tongue cancer, astrocytoma, small cell lung cancer, pediatric brain cancer, pediatric 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 , endometrial cancer, uterine sarcoma, prostate cancer, metastatic bone cancer, metastatic brain cancer, mediastinal cancer, colon cancer, rectal carcinoid, vaginal cancer, spinal cancer, acoustic neuroma, pancreatic cancer, salivary gland cancer, Kaposi's sarcoma, Paget's disease, tonsillar cancer, squamous cell carcinoma, lung adenocarcinoma, lung cancer, lung squamous cell carcinoma, skin cancer, anal cancer, rhabdomyosarcoma, laryngeal cancer, pleural cancer, and thymic cancer. 、 The cancer disease may be, but is 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) and acute myeloid leukemia), pancreatic cancer, colorectal cancer, lung cancer, colon cancer, or multiple myeloma. Meanwhile, the human immunodeficiency virus infection disease may be, but is not limited to, acquired immune deficiency syndrome (AIDS). Furthermore, the human immunodeficiency virus may be, but is not limited to, human immunodeficiency virus-1 (HIV-1), the most common and highly pathogenic variant.

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

[0188] The compositions of the present invention may further comprise a pharmaceutically acceptable carrier, diluent, or excipient, and may be formulated into various forms, such as oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, or sterile injection solutions, according to the intended purpose, and may be administered orally or via various routes, including intravenous, intraperitoneal, subcutaneous, rectal, and topical administration. Examples of suitable carriers, excipients, or diluents contained 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. The composition of the present invention may further contain fillers, anti-agglomerating agents, lubricants, wetting agents, flavorings, emulsifiers, preservatives, and the like.

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

[0190] Oral liquid preparations include suspensions, oral liquids, emulsions, syrups, etc., and may contain various excipients such as wetting agents, sweeteners, flavoring agents, preservatives, etc. in addition to water and liquid paraffin, which are frequently used simple diluents.

[0191] Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and ethyl oleate. Injectable esters such as are used. Suppository bases include witepsol, macrogol, twin 61, cocoa butter, laurin butter, glycerogelatin, etc. On the other hand, injections may contain conventional additives such as solubilizers, isotonicity agents, suspending agents, emulsifiers, stabilizers, preservatives, etc.

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

[0193] The terms "compound of the first aspect" and "pharmaceutically acceptable salt" of the present invention are as defined above.

[0194] The term "individual" as used herein refers to any animal, including monkeys, cows, horses, sheep, pigs, chickens, turkeys, quails, cats, dogs, mice, rats, rabbits, or guinea pigs, including humans, that are suffering from or may develop the viral infectious disease, and administration of the pharmaceutical composition of the present invention to an individual can effectively prevent or treat the disease. The pharmaceutical composition of the present invention can be administered in conjunction with an existing therapeutic agent.

[0195] The term "administration" as used herein means providing a predetermined substance to a patient by any suitable method. The administration route of the composition of the present invention can be any common route as long as it can deliver the substance to the target tissue. Administration can be by, but is not limited to, intraperitoneal, intravenous, intramuscular, subcutaneous, intradermal, oral, topical, intranasal, pulmonary, or rectal administration. The pharmaceutical composition of the present 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 infusion injection. Injectable preparations can be prepared using aqueous solvents such as saline and Ringer's solution, or non-aqueous solvents such as vegetable oils, higher fatty acid esters (e.g., ethyl oleate), and alcohols (e.g., ethanol, benzyl alcohol, propylene glycol, glycerin), and can contain pharmaceutical carriers such as stabilizers to prevent deterioration (e.g., ascorbic acid, sodium bisulfite, sodium metabisulfite, BHA, tocopherol, EDTA), emulsifiers, buffers for pH adjustment, and preservatives to prevent microbial growth (e.g., phenylmercuric nitrate, thimerosal, benzalkonium chloride, phenol, cresol, benzyl alcohol, etc.).

[0196] The term "therapeutically effective amount" used in combination with an active ingredient in the present invention means an amount of a triazolomethylurea derivative compound, or a pharmaceutically acceptable salt thereof, effective for preventing or treating a target disease.

[0197] The pharmaceutical composition of the present invention may further contain, as an active ingredient, a known drug used for the prevention or treatment of each known disease in addition to the compound of the present invention or a pharmaceutically acceptable salt thereof, depending on the type of disease to be prevented or treated. For example, when used for the prevention or treatment of viral infections, the pharmaceutical composition of the present invention may further contain, as an active ingredient, a known drug in addition to the compound of the present invention or a pharmaceutically acceptable salt thereof, and may be used in combination with other known therapies for the treatment of these diseases.

[0198] The compositions of the present invention are administered in a pharmaceutically effective amount. The term "pharmaceutically effective amount" as used herein refers to an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to any medical treatment, without causing adverse effects. The effective dose level can be determined based on factors including the patient's health status, the type and severity of the disease, the activity of the drug, sensitivity to the drug, the method, time, route and excretion rate of administration, duration of treatment, coadministration or concurrent use of other drugs, and other factors well known in the medical field. The compositions of the present invention can be administered as an individual therapeutic agent or in combination with other therapeutic agents, and can be administered sequentially or simultaneously with conventional therapeutic agents, in single or multiple administrations. Taking all of the above factors into consideration, it is important to administer an amount that can achieve maximum efficacy at a minimum dose without adverse effects, which can be easily determined by one skilled in the art.

[0199] For example, the dosage may increase or decrease depending on the route of administration, severity of the disease, sex, body weight, age, etc., and therefore the above dosage does not limit the scope of the present invention in any way.

[0200] in particular 、 The effective amount of the compound in the composition of the present invention varies depending on the age, sex, and weight of the patient, and is generally 1 to 100 mg per kg of body weight, preferably 5 to 60 mg, administered daily or every other day, or in 1 to 3 divided doses per day. However, since the amount may increase or decrease depending on the route of administration, severity of the disease, sex, weight, age, etc., the above dosage does not limit the scope of the present invention in any way.

[0201] Hereinafter, the present invention will be described in detail with reference to examples to facilitate understanding of the present invention. However, the examples according to the present invention may be modified into various other forms, and the scope of the present invention should not be construed as being limited to the following examples. The examples of the present invention are provided to more completely explain the present invention to those having average knowledge in the field to which the present invention pertains.

[0202] Preparation of the Compound of the Present Invention The synthesis processes of some compounds of the present invention are described below. Compounds not mentioned below can be prepared by the same method except for the starting materials, intermediates and / or reactants.

[0203] Some intermediates, particularly CDK inhibitor moieties, can be prepared by the methods disclosed in Korean Patent No. 1893879, the entire contents of which are incorporated herein by reference.

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

[0205] [ka]

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

[0207] Example 1 Synthesis of N-((1r,3r)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)acetamido)hexanoyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide (Compound 1)

[0208] [ka]

[0209] Step 1: Synthesis of tert-butyl 4-((9-((1s,3s)-3-(6-methylpicolinamido)cyclobutyl)-9H-purin-6-yl)amino)piperidine-1-carboxylate (Intermediate A-1) N-((1s,3s)-3-(6-chloro-9H-purin-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 stirred at 90 °C for 3 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure and purified using silica gel column chromatography to obtain the desired 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-(piperidin-4-ylamino)-9H-purin-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. The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to give the desired intermediate A-2 (143 mg, 0.35 mmol, quantitative) 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-methylpicolinamido)cyclobutyl)-9H-purin-6-yl)amino)piperidin-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·HO (40 mg, 0.28 mmol) were dissolved in DMF (1 mL), and DIPEA (0.2 mL, 1.25 mmol) was added. The mixture was stirred at room temperature for 12 hours. The reaction 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 under reduced pressure and purified using silica gel column chromatography to obtain the desired 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)piperidin-4-yl)amino)-9H-purin-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 stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to give the desired 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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)acetamido)hexanoyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide (Compound 1) Intermediate A-4 (10 mg, 0.019 mmol), (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycine (6 mg, 0.019 mmol), EDCI·HCl (4 mg, 0.021 mmol), and HOBt·HO (3 mg, 0.021 mmol) were dissolved in DMF (1 mL). DIPEA (0.02 mL, 0.095 mmol) was added and the mixture was stirred at room temperature for 12 hours. The reaction 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 under reduced pressure and purified using silica gel column chromatography to obtain the desired 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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)acetamido)hexanoyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide (Compound 2)

[0219] [ka]

[0220] Compound 2 was synthesized in the same manner as in Example 1 above, except that CRBN binder 1 was replaced with (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycine (CRBN binder 2).

[0221] Example 3 Synthesis of N-((1r,3r)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetamido)hexanoyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide (Compound 3)

[0222] [ka]

[0223] Compound 3 was synthesized in the same manner as in Example 1, except that CRBN binder 1 was replaced with 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetic acid (CRBN binder 3).

[0224] Example 4 Synthesis of N-((1r,3r)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)hexanoyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide (Compound 4)

[0225] [ka]

[0226] Synthesis was carried out in the same manner as in Example 1, except that 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)hexanoyl)piperidin-4-yl)amino)-9H-purin-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-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione (22 mg, 0.08 mmol) and DIPEA (0.04 mL, 0.23 mmol) were added. The mixture was stirred 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, and the residue was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography to obtain the desired 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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexanoyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide (Compound 6)

[0231] [ka]

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

[0233] Compounds 7 to 153 were synthesized using the corresponding linkers by the same or similar methods as in Examples 1 to 6. The following describes additional intermediates and synthetic methods for the compounds, and compounds for which no specific method is specified were synthesized using the corresponding intermediates and appropriate reactions.

[0234] Example 7 Synthesis of N-((1s,3s)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide (Compound 154)

[0235] [ka]

[0236] Step 1: Synthesis of (1s,3s)-3-(6-chloro-9H-purin-9-yl)cyclobutan-1-amine hydrochloride (Intermediate B-1) Intermediate B (tert-butyl (1s,3s)-3-(6-chloro-9H-purin-9-yl)cyclobutylcarbamate, 5.7 g, 17.6 mmol) was dissolved in dichloromethane (20 mL), and 4N hydrochloric acid in 1,4-dioxene (53 mmol) was added. The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to give the desired 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-purin-9-yl)cyclobutyl)acetamide (Intermediate B-2) Intermediate B-1 (650 mg, 2.4988 mmol) was dissolved in dichloromethane (10 mL), and then TEA (1.044 mL) was added. Acetic anhydride (0.354 mL) was added and stirred at room temperature. After the reaction was completed, 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 purified by silica gel column chromatography to obtain the desired 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-purin-6-yl)amino)methyl)piperidine-1-carboxylate (Intermediate B-3) The reaction was carried out in the same manner as in Step 1 of Example 1, except that intermediate B-2 (170 mg, 0.6398 mmol) and tert-butyl 4-(aminomethyl)piperidine-1-carboxylate (136 mg, 0.9597 mmol) were used as reactants, and the resulting mixture was separated and purified to give the desired intermediate B-3 (256 mg, 90%) 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-((piperidin-4-ylmethyl)amino)-9H-purin-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, to obtain the desired Intermediate B-4 (214 mg) 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-purin-6-yl)amino)methyl)piperidin-1-yl)methyl)piperidine-1-carboxylate (Intermediate B-5) Intermediate B-4 (210 mg, 0.5527 mmol) was dissolved in dichloromethane (20 mL), and then DIPEA (144 μL) and tert-butyl 4-formylpiperidine-1-carboxylate (188 mg, 0.8291 mmol) were added and stirred. NaBH(OAC) (152 mg, 0.7185 mmol) was added and stirred overnight at room temperature. Upon completion of the reaction, the solvent was removed by concentration under reduced pressure, and the mixture was purified by silica gel column chromatography to obtain the desired 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-(piperidin-4-ylmethyl)piperidin-4-yl)methyl)amino)-9H-purin-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, to obtain the desired Intermediate B-6 (211 mg) 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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide (Compound 154) The reaction was carried out in the same manner as in Step 3 of Example 1, except that intermediate B-6 (20 mg, 0.0419 mmol) and CRBN binder 3 (16 mg, 0.0503 mmol) were used, and the product was separated and purified to obtain the desired 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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide (Compound 155)

[0250] [ka]

[0251] Compound 154 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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide (Compound 156)

[0253] [ka]

[0254] Compound 154 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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide (Compound 157)

[0256] [ka]

[0257] Compound 154 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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide (Compound 159)

[0262] [ka]

[0263] Compound 154 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 corresponding linkers in the same or similar manner as compounds 155-160.

[0265] Preparation Example 1: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(4-(piperidin-4-ylmethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide hydrochloride (Intermediate C-6)

[0266] [ka]

[0267] Step 1: Synthesis of N-((1s,3s)-3-(6-chloro-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide (Intermediate C-2) Intermediate B-1 (500 mg, 1.92 mmol) was dissolved in dichloroethane (15 mL), and then 2-phenylacetic acid chloride (508 μL, 3.84 mmol) and DIPEA (1.4 mL, 7.68 mmol) were added and stirred at room temperature for 12 hours. After the reaction was completed, 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 purified by silica gel column chromatography to obtain the desired 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-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazine-1-carboxylate (Intermediate C-3) The reaction was carried out in the same manner as in Step 1 of Example 1, except that intermediate C-2 (750 mg, 2.194 mmol) and tert-butyl 4-(4-aminophenyl)piperazine-1-carboxylate (1.1 g, 3.949 mmol) were used, and the product was separated and purified to obtain the desired intermediate C-3 (1.0 g) as an ivory 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-(piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide hydrochloride (Intermediate C-4) The reaction was carried out in the same manner as in Step 1-1 of Example 1, except that Intermediate C-3 (1.0 g, 1.71 mmol) was used, to obtain the desired Intermediate C-4 (850 mg) 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-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)methyl)piperidine-1-carboxylate (Intermediate C-5) Intermediate C-4 (100 mg, 0.192 mmol) was dissolved in dichloromethane (10 mL), and then DIPEA (100 μL, 0.576 mmol) and tert-butyl 4-formylpiperidine-1-carboxylate (82 mg, 0.385 mmol) were added and stirred. NaBH(OAc) (142 mg, 0.672 mmol) was added and stirred at room temperature for 12 hours. Upon completion of the reaction, the solvent was removed by concentration under reduced pressure, and the mixture was purified by silica gel column chromatography to obtain the desired 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] Step 5: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(4-(piperidin-4-ylmethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide hydrochloride (Intermediate C-6) The reaction was carried out in the same manner as in Step 2-1 of Example 1, except that Intermediate C-5 (90 mg, 0.132 mmol) was used, to obtain the desired Intermediate C-6 (75 mg) 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] Production Example 2: Synthesis of N-((1s,3s)-3-(6-((4-(4-(7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-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-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate (Intermediate C-7) Intermediate C-7 was synthesized in the same manner as in Step 4 of Preparation 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)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (Intermediate C-8) Intermediate C-7 was synthesized in the same manner as in Step 5 of Preparation Example 1.

[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] Production Example 3: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(4-(2-(piperidin-4-yl)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-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-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-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)piperidin-4-yl)acetic acid (56 mg, 0.231 mmol) were used, and the product was separated and purified to obtain the desired 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-(piperidin-4-yl)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide hydrochloride (Intermediate C-10) Intermediate C-7 was synthesized in the same manner as in Step 5 of Preparation Example 1.

[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] Production Example 4: Synthesis of N-((1s,3s)-3-(6-((4-(4-(((1r,4r)-4-(aminomethyl)cyclohexyl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-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-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)methyl)cyclohexyl)methyl)carbamate (Intermediate C-11) Intermediate C-4 (30 mg, 0.0577 mmol) was dissolved in DMF (5 mL), and 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. The mixture was stirred at 70 °C for 12 hours. The reaction 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 under reduced pressure and purified using silica gel column chromatography to obtain the desired intermediate C-11 (17 mg, 34%) 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)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (Intermediate C-12) Intermediate C-7 was synthesized in the same manner as in Step 5 of Preparation Example 1.

[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] Production Example 5: Synthesis of 6-methyl-N-((1s,3s)-3-(6-((3-(4-(piperidin-4-ylmethyl)piperazin-1-yl)propyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide hydrochloride (Intermediate D-4)

[0296] [ka]

[0297] Step 1: Synthesis of tert-butyl 4-(3-((9-((1s,3s)-3-(6-methylpicolinamido)cyclobutyl)-9H-purin-6-yl)amino)propyl)piperazine-1-carboxylate (Intermediate D-1) Intermediate D-1 was synthesized 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-(piperazin-1-yl)propyl)amino)-9H-purin-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-methylpicolinamido)cyclobutyl)-9H-purin-6-yl)amino)propyl)piperazin-1-yl)methyl)piperidine-1-carboxylate (Intermediate D-3) Intermediate D-2 (150 mg, 0.333 mmol) was dissolved in methanol (25 mL), followed by the addition of tert-butyl 4-formylpiperidine-1-carboxylate (106 mg, 0.50 mmol) and acetic acid (0.5 mL) and stirring for 30 minutes. NaBH3CN (125 mg, 1.98 mmol) was slowly added to the reaction solution, followed by stirring 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 purified using silica gel column chromatography to obtain the desired 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-(piperidin-4-ylmethyl)piperazin-1-yl)propyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide hydrochloride (Intermediate D-4) Intermediate D-4 was synthesized in the same manner as in Step 5 of Preparation 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] Production Example 6: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(4-(3-(piperazin-1-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-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-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)propyl)piperazine-1-carboxylate (Intermediate C-13) Intermediate C-13 was synthesized in the same manner as in Step 1 of Preparation 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-purin-9-yl)cyclobutyl)acetamide hydrochloride (Intermediate C-14) Intermediate C-14 was synthesized in the same manner as in Step 5 of Preparation 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] Preparation Example 7: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(4-(2-(piperidin-4-yloxy)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-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-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)ethoxy)piperidine-1-carboxylate (Intermediate C-15) Intermediate C-13 was synthesized in the same manner as in Step 1 of Preparation Example 4.

[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-(piperidin-4-yloxy)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide hydrochloride (Intermediate C-16) Intermediate C-14 was synthesized in the same manner as in Step 5 of Preparation Example 1.

[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] Preparation Example 8: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(4-(3-(piperidin-4-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-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-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)propyl)piperidine-1-carboxylate (Intermediate C-17) Intermediate C-17 was synthesized in the same manner as in Step 1 of Preparation 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-(piperidin-4-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide hydrochloride (Intermediate C-18) Intermediate C-18 was synthesized in the same manner as in Step 1 of Preparation 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] Production Example 9: Synthesis of N-((1s,3s)-3-(6-((4-(4-(6-azaspiro[3.4]octan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-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-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)-6-azaspiro[3.4]octane-6-carboxylate (Intermediate C-19) Intermediate C-19 was synthesized in the same manner as in Step 2 of Preparation 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] Step 2: Synthesis of N-((1s,3s)-3-(6-((4-(4-(6-azaspiro[3.4]octan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (Intermediate C-20) Intermediate C-20 was synthesized in the same manner as in Step 5 of Preparation 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] Production Example 10: Synthesis of N-((1s,3s)-3-(6-((4-(4-(7-(azetidin-3-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-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-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate (Intermediate C-21) Intermediate C-21 was synthesized in the same manner as in Step 2 of Preparation 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)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (Intermediate C-22) Intermediate C-22 was synthesized in the same manner as in Step 5 of Preparation 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-butyl 3-(2-(4-(4-((9-((1s,3s)-3-(2-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)-7-azaspiro[3.5]nonan-7-yl)azetidine-1-carboxylate (Intermediate C-23) Intermediate C-23 was synthesized in the same manner as in Step 4 of Preparation 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-(azetidin-3-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (Intermediate C-24) Intermediate C-24 was synthesized in the same manner as in Step 5 of Preparation 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] Production Example 11: Synthesis of N-((1s,3s)-3-(6-((4-(4-(7-(azetidin-3-ylmethyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-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-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)-7-azaspiro[3.5]nonan-7-yl)methyl)azetidine-1-carboxylate (Intermediate C-25) Intermediate C-25 was synthesized in the same manner as in Step 1 of Preparation 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-(azetidin-3-ylmethyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide (Intermediate C-26) Intermediate C-26 was synthesized in the same manner as in Step 5 of Preparation Example 1.

[0344] 1 H 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] Preparation Example 12: Synthesis of 2-phenyl-N-((1s,3s)-3-(6-((4-(1-(piperidin-4-ylmethyl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide hydrochloride (Intermediate E-4)

[0346] [ka]

[0347] Step 1: Synthesis of tert-butyl 4-(4-((9-((1s,3s)-3-(2-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperidine-1-carboxylate (Intermediate E-1) Intermediate E-1 was synthesized in the same manner as in Step 2 of Preparation 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-(piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide hydrochloride (Intermediate E-2) Intermediate E-2 was synthesized in the same manner as in Step 3 of Preparation 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.

[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-(piperidin-4-ylmethyl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide hydrochloride (Intermediate E-4) Intermediate E-4 was synthesized in the same manner as in Step 5 of Preparation 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] Production Example 13: Synthesis of N-((1s,3s)-3-(6-((4-(1-(7-azaspiro[3.5]nonan-2-yl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (Intermediate E-6)

[0356] [ka]

[0357] Step 1: tert-butyl 2-(4-(4-((9-((1s,3s)-3-(2-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperidin-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate (Intermediate E-5) Intermediate E-5 was synthesized in the same manner as in Step 4 of Preparation 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)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide hydrochloride (Intermediate E-6) Intermediate E-6 was synthesized in the same manner as in Step 5 of Preparation 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-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxybenzoyl)piperidin-4-yl)methyl)piperazin-1-yl)phenylamino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide (Compound 186)

[0362] [ka]

[0363] The reaction was carried out in the same manner as in Step 3 of Example 1, except that intermediate C-6 (10 mg, 0.0162 mmol) and 3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxybenzoic acid (CRBN binder 8, 5.2 mg, 0.0194 mmol) were used, and the product was separated and purified to obtain the desired 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 to 479 were synthesized in the same manner as compound 186 using the corresponding starting materials and CRBN binder.

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

[0367] Experimental Example 2: Evaluation of CDK proteolytic activity To evaluate the CDK proteolytic activity of the compounds according to the present invention, the following experiment was carried out.

[0368] MDA-MB-231 cells were plated in 6-well plates at 5 × 10 5Each well was injected with 100 nM, 1 μM, or 10 μM of compound. The next day, each well was treated with compound at a final concentration of 100 nM, 1 μM, or 10 μM. Control wells were treated with the same amount of DMSO as the compound. After 16 hours of treatment, cells were harvested 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). Cell lysates were quantified and separated by size using polyacrylamide gel electrophoresis (SDS-PAGE). Western blots were then performed using antibodies recognizing CDK2, CDK9, and tubulin, respectively. The results of Western blotting were quantitatively analyzed using the ImageJ program, and representative images of the experimental results are shown in Figure 1. The enzyme degradation ability for CDK2 and CDK9 was calculated as a residual rate, and is 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, the following experiment was carried out.

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

[0389] Experimental Example 4: Evaluation of CDK protein inhibition In order to evaluate the inhibition of CDK2 and CDK9 protein activity of the compounds according to the present invention, experiments were conducted using KINOMEscan Technology provided by Eurofins, and the results of 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 exhibited relatively high degradation activity. This suggests that a pharmaceutical composition for treating CDK2 and / or CDK9-mediated diseases containing the compounds of the examples of the present invention as active ingredients can be provided.

[0394] From the above description, those skilled in the art to which the present invention pertains will understand that the present invention may be embodied in other specific forms without changing the technical spirit or essential characteristics thereof. In this regard, it should be understood that the above-described embodiments are merely illustrative and not limiting. The scope of the present invention should be interpreted as including within the meaning and scope of the claims below, and all modifications and variations derived from the equivalent concepts thereof, rather than the above detailed description.

Claims

1. A compound of the following formula 1 or a pharmaceutically acceptable salt thereof: 【Chemical 1】 In the above Chemical Formula 1, R １ 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- to 10-membered heterocycloalkyl, or —C １－３ alkyl-3-10 membered heterocycloalkyl, where 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 , -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 independently represent hydrogen, halogen, amino, C １－６ Alkyl, halo-C １－６ Alkyl, C ６－１０ Aryl, 5-10 membered heteroaryl, C ３－１０ cycloalkyl or 3- to 10-membered heterocycloalkyl; A is a moiety that acts as an exit vector, L is a linker, ELBs are E3 ubiquitin ligase binders.

2. The ELB is a compound of claim 1 having the structure of Formula 2: 【Chemistry 2】 In the above Chemical Formula 2, Cy is C ６－１０ aryl, 5-10 membered heteroaryl or 5-10 membered heterocycloalkyl; k is 0 to 2; X is N or C; R ２ is absent, hydrogen, deuterium (D), or C １ -C ３ Alkyl; The aryl, heteroaryl or heterocycloalkyl may be unsubstituted or substituted with oxo, halogen, nitro, amino, hydroxy, carboxy, C １－６ Alkyl, or C １－６ and substituted with one or more selected from the group consisting of alkoxy.

3. The compound of claim 2, wherein the formula 2 has any one of the following structures: 【Chemistry 3】 (R ３ is hydrogen or halogen, and X ２ is CH or N).

4. The compound of claim 2, wherein the formula 2 has any one of the following structures: 【Chemistry 4】 。

5. The R １ is C １－６ Alkyl, -C １－３ Alkyl-phenyl, phenyl, -C １－３ alkyl-pyridyl, or pyridyl, where phenyl or pyridyl is unsubstituted or １－３ Alkyl, halogen, cyano, and halo-C １－３ 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, substituted with one or more substituents selected from the group consisting of alkyl.

6. The R １ 2. The compound of claim 1, wherein: 【Chemistry 5】

7. 2. The compound of claim 1, wherein A has the structure of Formula 3: 【Chemistry 6】 In the above Chemical Formula 3, Cy １ is unsubstituted or C １－３ Alkyl-substituted C ６－１０ aryl or 5-10 membered heteroaryl, Cy ２ is a 3- to 10-membered heterocycloalkyl; l is an integer of 0 to 4, m, n, and p are each independently 0 or 1, excluding the case where all are 0.

8. 8. The compound of claim 7, wherein A is any one of the following structures: 【Chemistry 7】 。

9. the linker is -L1-L2-; L2 is direct connection, 【Chemistry 8】 and L1 is 【Chemistry 9】 or 【Chemistry 10】 and where: q, t, v, x and z are each independently 0 or 1; r, s, u, and y are each independently an integer from 0 to 6; Ch is C １－４ Alkenyl or C １－４ is alkynyl, Cy ３ and Cy ４ are independently absent, 3-10 membered heterocycloalkyl or C ３－１０ 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, which is cycloalkyl.

10. 10. The compound of claim 9, wherein L1 has any one of the following structures: 【Chemistry 11】

11. The compound is N-((1s,3s)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)acetamido)hexanoyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)acetamido)hexanoyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetamido)hexanoyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)hexanoyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)hexanoyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexanoyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetamido)ethoxy)ethoxy)acetyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)ethoxy)ethoxy)acetyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)acetamido)ethoxy)ethoxy)acetyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)acetamido)ethoxy)ethoxy)acetyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)ethoxy)ethoxy)acetyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)acetyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)acetamido)hexyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)acetamido)hexyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetamido)hexyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)hexyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)hexyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)acetamido)ethoxy)ethoxy)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)acetamido)ethoxy)ethoxy)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetamido)ethoxy)ethoxy)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)ethoxy)ethoxy)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)ethoxy)ethoxy)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-(2-(2,4-dioxocyclohexyl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(3-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperazin-1-yl)propyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(3-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperazin-1-yl)propyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(3-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperazin-1-yl)propyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(3-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperazin-1-yl)propyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)propyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperazin-1-yl)propyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)oxy)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)oxy)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)oxy)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)oxy)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)oxy)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)oxy)ethyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)acetyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)acetyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)acetyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)acetyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)acetyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((1-(2-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)acetyl)piperidin-4-yl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)acetamido)hexanoyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)acetamido)hexanoyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetamido)hexanoyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)hexanoyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)hexanoyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexanoyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetamido)ethoxy)ethoxy)acetyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)ethoxy)ethoxy)acetyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)acetamido)ethoxy)ethoxy)acetyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)acetamido)ethoxy)ethoxy)acetyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)acetyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)ethoxy)ethoxy)ethyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)acetamido)ethoxy)ethoxy)ethyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetamido)ethoxy)ethoxy)ethyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-(((1-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)acetamido)ethoxy)ethoxy)ethyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)methoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)methoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(3-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperazin-1-yl)propoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(3-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperazin-1-yl)propoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(3-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperazin-1-yl)propoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(3-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperazin-1-yl)propoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)propoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperazin-1-yl)propoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)methoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)methoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(3-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperazin-1-yl)propoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(3-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperazin-1-yl)propoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(3-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperazin-1-yl)propoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(3-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperazin-1-yl)propoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)propoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperazin-1-yl)propoxy)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-((3-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperazin-1-yl)propyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-((3-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperazin-1-yl)propyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-((3-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperazin-1-yl)propyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-((3-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperazin-1-yl)propyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-((3-(4-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)propyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-((3-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)propyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-((3-(4-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)propyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1r,3r)-3-(6-((3-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)propyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide, N-((1s,3s)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide, N-((1s,3s)-3-(6-(((1-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide, N-((1s,3s)-3-(6-(((1-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide, N-((1s,3s)-3-(6-(((1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide, N-((1s,3s)-3-(6-(((1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)benzyl)amino)-9H-purin-9-yl)cyclobutyl)acetamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)methyl)piperazin-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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, 2,6-dichloro-N-((1s,3s)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-(((1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-(((1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-(((1-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-(((1-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-(((1-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxybenzoyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)benzofuran-6-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(3-((1-(2,6-dioxopiperidin-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)amino)phenyl)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(1-(2,6-dioxopiperidin-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxybenzoyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)benzofuran-6-carbonyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(3-((1-(2,6-dioxopiperidin-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)amino)phenyl)acetyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(1-(2,6-dioxopiperidin-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)piperidine-4-carbonyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxybenzoyl)piperidin-4-yl)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)benzofuran-6-carbonyl)piperidin-4-yl)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(3-((1-(2,6-dioxopiperidin-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)amino)phenyl)acetyl)piperidin-4-yl)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(1-(2,6-dioxopiperidin-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)piperidine-4-carbonyl)piperidin-4-yl)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, 3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxy-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)methyl)cyclohexyl)methyl)benzamide, 3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)methyl)cyclohexyl)methyl)benzofuran-6-carboxamide, 2-(3-((1-(2,6-dioxopiperidin-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)amino)phenyl)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)methyl)cyclohexyl)methyl)acetamide, 1-(1-(2,6-dioxopiperidin-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)methyl)cyclohexyl)methyl)piperidine-4-carboxamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, 2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)methyl)cyclohexyl)methyl)acetamide, 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)methyl)cyclohexyl)methyl)acetamide, 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)methyl)cyclohexyl)methyl)acetamide, 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)methyl)cyclohexyl)methyl)acetamide, 2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)methyl)cyclohexyl)methyl)acetamide, N-((1s,3s)-3-(6-((4-(4-(((1r,4r)-4-(((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)methyl)cyclohexyl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, 2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)-N-(((1r,4r)-4-((4-(4-((9-((1s,3s)-3-(2-phenylacetamido)cyclobutyl)-9H-purin-6-yl)amino)phenyl)piperazin-1-yl)methyl)cyclohexyl)methyl)acetamide, N-((1s,3s)-3-(6-((3-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperazin-1-yl)propyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((3-(4-((1-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxybenzoyl)piperidin-4-yl)methyl)piperazin-1-yl)propyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((1-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)propyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((3-(4-((1-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)propyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperazin-1-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperazin-1-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperazin-1-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperazin-1-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxybenzoyl)piperazin-1-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperazin-1-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperazin-1-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperazin-1-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)acetyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(((1r,4r)-4-(((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)amino)methyl)cyclohexyl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)oxy)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)oxy)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)oxy)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)oxy)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxybenzoyl)piperidin-4-yl)oxy)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)oxy)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)oxy)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)oxy)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxybenzoyl)piperidin-4-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)oxy)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)-6-azaspiro[3.4]octan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)-6-azaspiro[3.4]octan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)-6-azaspiro[3.4]octan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(6-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)-6-azaspiro[3.4]octan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(6-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxybenzoyl)-6-azaspiro[3.4]octan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(6-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)-6-azaspiro[3.4]octan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(6-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)-6-azaspiro[3.4]octan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)azetidin-3-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidin-3-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxybenzoyl)azetidin-3-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)azetidin-3-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)azetidin-3-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-((1-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)azetidin-3-yl)methyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-((1-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)azetidin-3-yl)methyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)azetidin-3-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)azetidin-3-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)azetidin-3-yl)methyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-((1-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxybenzoyl)azetidin-3-yl)methyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxybenzoyl)piperidin-4-yl)methyl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)-7-azaspiro[3.5]nonan-2-yl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)-7-azaspiro[3.5]nonan-2-yl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-4-methoxybenzoyl)-7-azaspiro[3.5]nonan-2-yl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperidin-4-yl)methyl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperidin-4-yl)methyl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)-7-azaspiro[3.5]nonan-2-yl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)-7-azaspiro[3.5]nonan-2-yl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)-7-azaspiro[3.5]nonan-2-yl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)-7-azaspiro[3.5]nonan-2-yl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)-7-azaspiro[3.5]nonan-2-yl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(1-(7-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-7-azaspiro[3.5]nonan-2-yl)piperidin-4-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-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-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-(3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)propanoyl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-((4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperazin-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-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-(7-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-(7-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-(7-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-(7-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)glycyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((4-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((4-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-((4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)oxy)acetyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((4-(4-((4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((4-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperidin-4-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)-7-azaspiro[3.5]nonan-7-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)-7-azaspiro[3.5]nonan-7-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(2-(4-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperazin-1-yl)-7-azaspiro[3.5]nonan-7-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)ethyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)ethyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(4-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperazin-1-yl)ethyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperidin-4-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidin-3-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)azetidin-3-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)azetidin-3-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)propyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)propyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperazin-1-yl)propyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)azetidin-3-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperidin-4-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(4-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperazin-1-yl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)azetidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)azetidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(2-(4-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperazin-1-yl)-7-azaspiro[3.5]nonan-7-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(2-(4-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperazin-1-yl)-7-azaspiro[3.5]nonan-7-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(4-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperazin-1-yl)ethyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(4-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperazin-1-yl)ethyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(4-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperazin-1-yl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(4-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperazin-1-yl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperazin-1-yl)propyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(4-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperazin-1-yl)propyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(3-(4-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperazin-1-yl)azetidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-((4-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperidin-4-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(3-(4-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperazin-1-yl)azetidin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidin-3-yl)methyl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(7-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-fluoropicolinamide, 6-chloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide, 6-cyano-N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperidin-4-yl)methyl)piperazin-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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, 2,6-dichloro-N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-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-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-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-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-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-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidin-3-yl)methyl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)ethyl)piperazin-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-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)ethyl)piperazin-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-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((4-(4-(1-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)butyl)piperidin-4-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperidin-4-yl)ethyl)piperazin-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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, 6-cyano-N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, 6-chloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide, 6-chloro-N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide, 6-cyano-N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide, 6-chloro-N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide, 6-cyano-N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide, N-((1s,3s)-3-(6-((2-(1-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-(3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)propyl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)propyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)butyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-fluoropicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-fluoropicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-fluoropicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)propyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-fluoropicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)butyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-fluoropicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-(7-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, 6-chloro-N-((1s,3s)-3-(6-((4-(4-((1-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide, 6-cyano-N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-(7-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)-2-methylphenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperazin-1-yl)-2-methylphenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)-2-methylphenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)-2-methylphenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((2-(1-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, 6-chloro-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide, 6-chloro-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide, 6-chloro-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide, 6-cyano-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide, 6-cyano-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(2-(1-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)ethyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(3-(1-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)propyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, N-((1s,3s)-3-(6-((2-(1-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperidin-4-yl)ethyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-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-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)ethyl)piperazin-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-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)benzamide, N-((1s,3s)-3-(6-((4-(4-(7-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-fluoropicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-fluoropicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-fluoropicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-(trifluoromethyl)picolinamide, 6-cyano-N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)picolinamide, 2,6-dichloro-N-((1s,3s)-3-(6-((4-(4-((4-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidine-3-carbonyl)piperazin-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-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperazin-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-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperazin-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-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(1-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperidine-4-carbonyl)piperidin-4-yl)methyl)piperazin-1-yl)-2-methylphenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, N-((1s,3s)-3-(6-((4-(4-((1-(3-(2,6-dioxopiperidin-3-yl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)piperidin-4-yl)methyl)piperazin-1-yl)-2-methylphenyl)amino)-9H-purin-9-yl)cyclobutyl)-6-methylpicolinamide, or N-((1s,3s)-3-(6-((4-(4-(7-(4-(4-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)but-2-yn-1-yl)-7-azaspiro[3.5]nonan-2-yl)piperazin-1-yl)phenyl)amino)-9H-purin-9-yl)cyclobutyl)-2-phenylacetamide 2. The compound of claim 1, wherein:

12. A first step of preparing a compound of formula 5 by reacting a compound of formula 4 below with a derivative of the A moiety containing an amine group at one end and a protecting group at the other end, followed by deprotection; The compound of Formula 5 is provided with a reactive functional group X at one end. ２ a second step of reacting the compound of formula 6 with a derivative of the L1 moiety containing a protecting group at the other end, followed by deprotection to provide a compound of formula 6; and The compound of Formula 5 is treated by adding a reactive functional group X ３ 12. A method for preparing the compound of any one of claims 1-11, or a pharmaceutically acceptable salt thereof, comprising a third step of reacting a CRBN binder comprising: 【Chemistry 12】 In the above Chemical Formulas 4 to 6, X １ , X ２ and X ３ are each independently halogen or hydroxy, The protecting group is tert-butoxycarbonyl, A' and L1' may be the same as A and L1, respectively, or may be in the form of a salt thereof.

13. The CRBN binder comprises: 【Chemistry 13】 The method according to claim 12, wherein the compound is any one selected from the group consisting of:

14. The first step is X １ is a halogen, in a lower alcohol solvent at 70°C to 100°C to react, and then deprotect the compound by treating with a strong acid solution in an organic solvent.

15. The second stage comprises: i) X ２ is a hydroxyl group, and reacting it with EDCI (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide), HOBt (hydroxybenzotriazole), and DIPEA (N,N-diisopropylethylamine) in an organic solvent at 15°C to 40°C, ii) X ２ is a halogen, and reacting in an organic solvent under basic conditions at 40°C to 80°C, iii) X ２ Compounds in which 1 is oxo were used, and DIPEA and sodium triacetoxyborohydride (NaBH(OAc) ３ ) at 15°C to 40°C, or iv) X ２ is oxo, sodium cyanoborohydride (NaBH ３ CN) at 15°C to 40°C, The method according to claim 12, wherein the deprotection is carried out by treating with a strong acid solution in an organic solvent.

16. The third stage is i) X ３ is a hydroxyl group, and reacting it with EDCI, HOBt, and DIPEA in an organic solvent at 15°C to 40°C; ii) X ３ The method according to claim 12, wherein the compound is a halogen, and the compound is reacted with DIPEA in an organic solvent at 70°C to 100°C.

17. A composition comprising a compound according to any one of claims 1 to 11 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

18. A pharmaceutical composition for inhibiting or degrading CDK2 (cyclin-dependent kinase 2), CDK9 (cyclin-dependent kinase 9), or both, comprising the compound according to any one of claims 1 to 11 or a pharmaceutically acceptable salt thereof as an active ingredient.

19. A pharmaceutical composition for preventing or treating cancer diseases or human immunodeficiency virus (HIV) infection diseases, comprising the compound according to any one of claims 1 to 11 or a pharmaceutically acceptable salt thereof as an active ingredient.

20. 20. The pharmaceutical composition of claim 19, 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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