Combination therapy with substituted 3-((3-aminophenyl)amino)piperidine-2,6-dione compounds

Abstract

Provided herein are methods of treating, preventing, managing, and / or ameliorating androgen receptor-mediated diseases with a combination of a 3-((3-aminophenyl)amino)piperidine-2,6-dione compound and a second agent.

Description

[Technical Field]

[0001] Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 63 / 424,014, filed November 9, 2022, the disclosure of which is incorporated herein by reference in its entirety.

[0002] Provided herein are methods of treating, preventing, managing, and / or ameliorating androgen receptor-mediated diseases with a 3-((3-aminophenyl)amino)piperidine-2,6-dione compound in combination with a second agent. Also provided herein are combinations of a 3-((3-aminophenyl)amino)piperidine-2,6-dione compound with a second agent for use in such methods. [Background technology]

[0003] Androgen receptor signaling is known to play an important role in the pathogenesis of prostate cancer and is also involved in the development of other androgen receptor-positive cancers (Non-Patent Document 1; Non-Patent Document 2; Non-Patent Document 3; Non-Patent Document 4). Inhibition of androgen receptor signaling by antiandrogens that antagonize the androgen receptor has been used or proposed for the treatment of prostate cancer. Exemplary compounds are disclosed in Patent Document 1. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] U.S. Patent No. 11,149,007 [Non-patent literature]

[0005] [Non-Patent Document 1] Chen Y et al.,Lancet Oncol,2009,10:981-91 [Non-patent document 2] Mills IG, Nat Rev Cancer,2014,14:187-98 [Non-patent document 3] Taplin ME,Nat Clin Pract Oncol,2007,4:236-44 [Non-patent document 4] Wirth MP et al.,Eur Urol,2007,51(2):306-13 Summary of the Invention [Problem to be solved by the invention]

[0006] There is a need for methods of treatment for androgen receptor-mediated diseases using combination therapy of a 3-((3-aminophenyl)amino)piperidine-2,6-dione compound and a second agent. [Means for solving the problem]

[0007] The compounds used in the methods herein are described in U.S. Patent No. 11,149,007, the disclosure of which is incorporated herein by reference in its entirety. In one embodiment, provided herein are methods for treating, preventing, managing, and / or ameliorating androgen receptor-mediated diseases by administering a compound of Formula I described herein in combination with one or more second agents selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor. Accordingly, provided herein are piperidinedione compounds for use in such methods, the methods comprising administering a piperidinedione compound in combination with one or more second agents selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor.

[0008] In certain embodiments, provided herein is a unit dosage form comprising a piperidinedione compound and a second agent selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor.

[0009] Also provided are pharmaceutical packs or kits containing a piperidinedione compound and one or more second agents selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor. Such pharmaceutical packs or kits can optionally be accompanied by notices in a format prescribed by a government agency regulating the manufacture, use, or sale of pharmaceuticals or biological products, which notice reflects approval by the agency for manufacture, use, or sale for human administration. The packs or kits can be labeled with information regarding the mode of administration, the order in which the drugs are administered (e.g., separately, sequentially, or simultaneously), and the like.

[0010] These and other aspects of the subject matter described herein will become evident upon reference to the following detailed description. DETAILED DESCRIPTION OF THE INVENTION

[0011] definition Generally, the nomenclature used herein and the laboratory procedures in organic chemistry, medicinal chemistry, and pharmacology described herein are those well known and commonly employed in the art. Unless otherwise defined, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Generally, the technical teachings of one embodiment can be combined with those disclosed in other embodiments provided herein.

[0012] As used herein, the terms "comprise" and "comprising" can be used interchangeably. The terms "comprise" and "comprising" should be interpreted as specifying the reference to the presence of the stated features or components, but do not exclude the presence or addition of one or more features or components or groups thereof. Furthermore, the terms "comprise" and "comprising" are intended to include examples encompassed by the term "consisting of." Thus, the term "consisting of" can be used in place of the terms "comprising" and "comprising" to provide more specific embodiments of the present invention.

[0013] The term "consisting of" means that the object has at least 90%, 95%, 97%, 98%, or 99% of the recited features or components that make it up. In another embodiment, the term "consisting of" excludes any other features or components from the scope of any subsequent recitation, except those that are not essential to the technical effect being achieved.

[0014] As used herein, the term "or" is to be interpreted as an inclusive "or" meaning any one or any combination. Thus, "A, B, or C" means any of the following: "A; B; C; A and B; A and C; B and C; A, B, and C." Exceptions to this definition occur only where combinations of elements, features, steps, or acts are inherently mutually exclusive in some way.

[0015] An "alkyl" group is a saturated, partially saturated, or unsaturated, straight-chain or branched, acyclic hydrocarbon having 1 to 10 carbon atoms, typically 1 to 8 carbon atoms, or in some embodiments, 1 to 6, 1 to 4, or 2 to 6 carbon atoms. In some embodiments, the alkyl group is a saturated alkyl group. Representative saturated alkyl groups include -methyl, -ethyl, -n-propyl, -n-butyl, -n-pentyl, and -n-hexyl, while saturated branched alkyls include -isopropyl, -sec-butyl, -isobutyl, -tert-butyl, -isopentyl, -neopentyl, tert-pentyl, -2-methylpentyl, -3-methylpentyl, -4-methylpentyl, -2,3-dimethylbutyl, and the like. In some embodiments, the alkyl group is an unsaturated alkyl group, also referred to as an alkenyl or alkynyl group. An "alkenyl" group is an alkyl group containing one or more carbon-carbon double bonds. An "alkynyl" group is an alkyl group containing one or more carbon-carbon triple bonds. Examples of unsaturated alkyl groups include, but are not limited to, vinyl, allyl, -CH=CH(CH), -CH=C(CH), -C(CH)=CH, -C(CH)=CH(CH), -C(CHCH)=CH, -C≡CH, -C≡C(CH), -C≡C(CHCH), -CHC≡CH, -CHC≡C(CH), and -CHC≡C(CHCH), among others. Alkyl groups can be substituted or unsubstituted.When an alkyl group described herein is described as "substituted," the alkyl group can be substituted with any of the following groups: halogen, hydroxy, alkoxy, cycloalkyloxy, aryloxy, heterocyclyloxy, heteroaryloxy, heterocycloalkyloxy, cycloalkylalkyloxy, aralkyloxy, heterocyclylalkyloxy, heteroarylalkyloxy, heterocycloalkylalkyloxy, oxo(=O), amino, alkylamino, cycloalkylamino, arylamino, heterocyclylamino, heteroarylamino, heterocycloalkylamino, ... and optionally substituted by alkylalkylamino, aralkylamino, heterocyclylalkylamino, heteroaralkylamino, heterocycloalkylalkylamino, imino, imido, amidino, guanidino, eneamino, acylamino, sulfonylamino, urea, nitrourea, oxime, hydroxylamino, alkoxyamino, aralkoxyamino, hydrazino, hydrazide, hydrazono, azido, nitro, thio (-SH), alkylthio, =S, sulfinyl, sulfonyl, aminosulfonyl, phosphonate, phosphinyl, acyl, formyl, carboxy, ester, carbamate, amido, cyano, isocyanato, isothiocyanato, cyanato, thiocyanato, or -B(OH).In certain embodiments, when an alkyl group described herein is described as "substituted," the alkyl group can be substituted with halogen (chloro, iodo, bromo, or fluoro), alkyl, hydroxyl, alkoxy, alkoxyalkyl, amino, alkylamino, carboxy, nitro, cyano, thiol, thioether, imine, imide, amidine, guanidine, enamine, aminocarbonyl, acylamino, phosphonate, phosphine, thiocarbonyl, sulfinyl, sulfone, sulfonamide, ketone, aldehyde, ester, urea, urethane, oxime, hydroxylamine, alkoxyamine, aralkoxyamine, N-oxide, hydrazine, hydrazide, hydrazone, azide, isocyanate, isothiocyanate, cyanate, thiocyanate, B(OH), or O(alkyl)aminocarbonyl, in addition to any substituent(s) found in the exemplary compounds and embodiments disclosed herein.

[0016] A "cycloalkyl" group is a saturated or partially saturated cyclic alkyl group of 3 to 10 carbon atoms, having a single ring or multiple fused or bridged rings, which may be optionally substituted. In some embodiments, a cycloalkyl group has 3 to 8 ring members, while in other embodiments, the number of ring carbon atoms ranges from 3 to 5, 3 to 6, or 3 to 7. In some embodiments, a cycloalkyl group is a saturated cycloalkyl group. Such saturated cycloalkyl groups include, by way of example, single ring structures such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 1-methylcyclopropyl, 2-methylcyclopentyl, 2-methylcyclooctyl, and the like, or multiple ring or bridged ring structures such as 1-bicyclo[1.1.1]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, adamantyl, and the like. In other embodiments, a cycloalkyl group is an unsaturated cycloalkyl group. Examples of unsaturated cycloalkyl groups include, among others, cyclohexenyl, cyclopentenyl, cyclohexadienyl, butadienyl, pentadienyl, and hexadienyl. The cycloalkyl group can be substituted or unsubstituted. Examples of such substituted cycloalkyl groups include cyclohexanol and the like.

[0017] An "aryl" group is an aromatic carbocyclic group of 6 to 14 carbon atoms, having a single ring (e.g., phenyl) or multiple condensed rings (e.g., naphthyl or anthryl). In some embodiments, aryl groups contain 6 to 14 carbons, and in other embodiments 6 to 12, and sometimes 6 to 10 carbon atoms in the ring portion of the group. Specific aryls include phenyl, biphenyl, naphthyl, and the like. Aryl groups can be substituted or unsubstituted. The phrase "aryl group" also includes groups containing condensed rings, such as fused aromatic aliphatic ring systems (e.g., indanyl, tetrahydronaphthyl, and the like).

[0018] A "heteroaryl" group is an aromatic ring system having 1 to 4 heteroatoms as ring atoms in the heteroaromatic ring system, with the remaining atoms being carbon atoms. In some embodiments, heteroaryl groups contain 3 to 6 ring atoms, and in other embodiments 6 to 9, and sometimes 6 to 10 atoms in the ring portion of the group. Suitable heteroatoms include oxygen, sulfur, and nitrogen. In certain embodiments, the heteroaryl ring system is monocyclic or bicyclic. Non-limiting examples include pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, benzisoxazolyl (e.g., benzo[d]isoxazolyl), thiazolyl, pyrrolyl, pyridazinyl, pyrimidyl, pyrazinyl, thiophenyl, benzothiophenyl, furanyl, benzofuranyl, indolyl (e.g., indolyl-2-onyl or isoindolin-1-onyl), azaindolyl (pyrrolopyridyl or 1H-pyrrolo[2,3-b]pyridyl), indazolyl, benzimidazolyl (e.g., 1H-benzo[d]imidazolyl), imidazopyridyl (e.g., Examples of heteroaryl groups include, but are not limited to, azabenzimidazolyl or 1H-imidazo[4,5-b]pyridyl), pyrazolopyridyl, triazolopyridyl, benzotriazolyl (e.g., 1H-benzo[d][1,2,3]triazolyl), benzoxazolyl (e.g., benzo[d]oxazolyl), benzothiazolyl, benzothiadiazolyl, isoxazolopyridyl, thianaphthalenyl, purinyl, xanthinyl, adeninyl, guaninyl, quinolinyl, isoquinolinyl (e.g., 3,4-dihydroisoquinolin-1(2H)-onyl), tetrahydroquinolinyl, quinoxalinyl, and quinazolinyl groups. Heteroaryl groups can be substituted or unsubstituted.

[0019] A "heterocyclyl" is an aromatic (also called heteroaryl) or non-aromatic cycloalkyl in which 1 to 4 of the ring carbon atoms are independently replaced with a heteroatom from the group consisting of O, S, and N. In some embodiments, heterocyclyl groups contain 3 to 10 ring members, while other such groups have 3 to 5, 3 to 6, or 3 to 8 ring members. A heterocyclyl can also be attached to other groups at any ring atom (i.e., any carbon atom or heteroatom of the heterocyclic ring). Heterocycloalkyl groups can be substituted or unsubstituted. Heterocyclyl groups include unsaturated, partially saturated, and saturated ring systems, such as imidazolyl, imidazolinyl, and imidazolidinyl (e.g., imidazolidin-4-one or imidazolidin-2,4-dionyl) groups. The term heterocyclyl includes fused ring species, including those containing fused aromatic and non-aromatic groups, such as 1-aminotetralin and 2-aminotetralin, benzotriazolyl (e.g., 1H-benzo[d][1,2,3]triazolyl), benzimidazolyl (e.g., 1H-benzo[d]imidazolyl), 2,3-dihydrobenzo[1,4]dioxinyl, and benzo[1,3]dioxolyl. The term also includes bridged polycyclic ring systems containing heteroatoms, such as, but not limited to, quinuclidyl. Representative examples of heterocyclyl groups include, but are not limited to, aziridinyl, azetidinyl, azepanyl, oxetanyl, pyrrolidyl, imidazolidinyl (e.g., imidazolidin-4-onyl or imidazolidin-2,4-dionyl), pyrazolidinyl, thiazolidinyl, tetrahydrothiophenyl, tetrahydrofuranyl, dioxolyl, furanyl, thiophenyl, pyrrolyl, pyrrolinyl, imidazolyl, imidazolinyl, pyrazolyl, pyrazolinyl, triazolyl, tetrazolyl, oxazolyl, benzisoxazolyl (e.g., benzo[d]isoxazolyl), thiazolyl, thiazolinyl, isothiazolyl, thiadiazolyl, oxadiazolyl, piperidyl, piperazinyl (e.g., piperazin-2-onyl), morpholinyl aryl, thiomorpholinyl, tetrahydropyranyl (e.g., tetrahydro-2H-pyranyl), tetrahydrothiopyranyl, oxathianyl, dioxyl, dithianyl, pyranyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, triazinyl, dihydropyridyl, dihydrodithionyl, dihydrodithionyl, 1,4-dioxaspiro[4.5]decanyl, homopiperazinyl, quinuclidyl, indolyl (e.g., indolyl-2-onyl or isoindolin-1-onyl), indolinyl, isoindolyl, isoindolinyl, azaindolyl (pyrrolopyridyl or 1H-pyrrolo[2,3-b]pyridyl), indazolyl, indolizinyl, benzotriazolyl (e.g., 1H-benzo[d][1,2,3]triazolyl), benzimidazolyl (e.g., 1H-benzo[d]imidazolyl or 1H-benzo[d]imidazol-2(3H)-onyl), benzofuranyl, benzothiophenyl, benzothiazolyl, benzoxadiazolyl, benzoxazinyl, benzodithiinyl, benzoxathiinyl, benzothiazolyl, dioxolyl, benzoxazolyl (i.e., benzo[d]oxazolyl), benzothiazolyl, benzothiadiazolyl, benzo[1,3]dioxolyl, pyrazolopyridyl (e.g., 1H-pyrazolo[3,4-b]pyridyl, 1H-pyrazolo[4,3-b]pyridyl), imidazopyridyl (e.g., azabenzimidazolyl or 1H-imidazo[4,5-b]pyridyl), triazolopyridyl, isoxazolopyridyl, purinyl, xanthinyl, adeninyl, guaninyl, quinolinyl, isoquinolinyl (e.g., 3,4-dihydroisoquinolin-1(2H)-onyl), quinolidinyl, quinoxalinyl, quinazolinyl, cinnolinyl, phthalazinyl, naphthyridinyl, pteridinyl, thianaphthalenyl, dihydrobenzothiazinyl, dihydrobenzofuranyl, dihydroindolyl, dihydrobenzodioxinyl, tetrahydroindolyl, tetrahydroindazolyl, tetrahydrobenzimidazolyl, tetrahydrobenzotriazolyl, tetrahydropyrrolopyridyl, tetrahydropyrazolopyridyl, tetrahydroimidazopyridyl, tetrahydrotriazolopyridyl, tetrahydropyrimidin-2(1H)-one, and tetrahydroquinolinyl groups. Representative non-aromatic heterocyclyl groups do not include fused ring species containing fused aromatic groups. Examples of non-aromatic heterocyclyl groups include aziridinyl, azetidinyl, azepanyl, pyrrolidyl, imidazolidinyl (e.g., imidazolidin-4-onyl or imidazolidin-2,4-dionyl), pyrazolidinyl, thiazolidinyl, tetrahydrothiophenyl, tetrahydrofuranyl, piperidyl, piperazinyl (e.g., piperazin-2-onyl), morpholinyl, thiomorpholinyl, tetrahydropyranyl (e.g., tetrahydro-2H-pyranyl), tetrahydrothiopyranyl, oxathianyl, dithianyl, 1,4-dioxaspiro[4.5]decanyl, homopiperazinyl, quinuclidyl, or tetrahydropyrimidin-2(1H)-one. Representative substituted heterocyclyl groups may be mono- or multiply substituted, including, but not limited to, pyridyl or morpholinyl groups that are di-, tri-, tetra-, pentapi-, or hexa-substituted, or di-substituted with various substituents such as those listed below.

[0020] As used herein, unless otherwise specified, a "cycloalkylalkyl" group is a group of the formula: -alkyl-cycloalkyl, where alkyl and cycloalkyl are defined above. Substituted cycloalkylalkyl groups can be substituted on the alkyl, the cycloalkyl, or both the alkyl and cycloalkyl portions of the group. Representative cycloalkylalkyl groups include, but are not limited to, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, cyclopentylpropyl, cyclohexylpropyl, and the like.

[0021] As used herein, unless otherwise specified, an "aralkyl" group is a group of the formula: -alkyl-aryl, where alkyl and aryl are defined above. Substituted aralkyl groups can be substituted on the alkyl, aryl, or both the alkyl and aryl portions of the group. Representative aralkyl groups include, but are not limited to, benzyl and phenethyl groups, and aralkyl groups in which the aryl group is fused to a cycloalkyl group (e.g., indan-4-ylethyl).

[0022] As used herein, unless otherwise specified, a "heterocyclylalkyl" group is a group of the formula: -alkyl-heterocyclyl, where alkyl and heterocyclyl are defined above. A "heteroarylalkyl" group is a group of the formula: -alkyl-heteroaryl, where alkyl and heteroaryl are defined above. A "heterocycloalkylalkyl" group is a group of the formula: -alkyl-heterocycloalkyl, where alkyl and heterocycloalkyl are defined above. Substituted heterocyclylalkyl groups can be substituted on the alkyl, the heterocyclyl, or both the alkyl and heterocyclyl portions of the group. Representative heterocyclylalkyl groups include, but are not limited to, morpholin-4-ylethyl, morpholin-4-ylpropyl, furan-2-ylmethyl, furan-3-ylmethyl, pyridin-3-ylmethyl, tetrahydrofuran-2-ylethyl, and indol-2-ylpropyl.

[0023] "Halogen" is fluorine, chlorine, bromine or iodine.

[0024] A "hydroxyalkyl" group is an alkyl group as defined above that is substituted with one or more hydroxy groups.

[0025] An "alkoxy" group is an --O-(alkyl), where alkyl is defined above.

[0026] An "alkoxyalkyl" group is an -(alkyl)-O-(alkyl), where alkyl is defined above.

[0027] An "amino" group is a group of the formula: -NH, -NH(R # ) or -N(R # )2 groups, and each R #are independently an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, an aryl group, an aralkyl group, a heterocyclyl group (e.g., a heteroaryl group or a heterocycloalkylalkyl group), or a heterocyclylalkyl group (e.g., a heteroarylalkyl group or a heterocycloalkylalkyl group), as defined above, each of which is independently substituted or unsubstituted.

[0028] In one embodiment, an "amino" group is an "alkylamino" group, which is a radical of the formula: -NH-alkyl or -N(alkyl), where each alkyl is independently defined above. The terms "cycloalkylamino," "arylamino," "heterocyclylamino," "heteroarylamino," "heterocycloalkylamino," and the like reflect the description of "alkylamino" above, with the term "alkyl" replaced by "cycloalkyl," "aryl," "heterocyclyl," "heteroaryl," "heterocycloalkyl," and the like, respectively.

[0029] A "carboxy" group is a radical of the formula: --C(O)OH.

[0030] As used herein, unless otherwise specified, an "acyl" group is a group of the formula: -C(O)(R # ) or —C(O)H, and R # is defined above. A "formyl" group is a radical of the formula: --C(O)H.

[0031] As used herein, unless otherwise specified, an "amide" group is a group of the formula: -C(O)-NH, -C(O)-NH(R # ), -C(O)-N(R # )2, -NH-C(O)H, -NH-C(O)-(R # ), -N(R # )-C(O)H or -N(R # )-C(O)-(R # ) group, and each R # are independently defined above.

[0032] In one embodiment, an "amide" group has the formula: -C(O)-NH, -C(O)-NH(R # ), -C(O)-N(R # )2 is an "aminocarbonyl" group, and each R # are independently defined above.

[0033] In one embodiment, an "amide" group has the formula: -NH-C(O)H, -NH-C(O)-(R # ), -N(R # )-C(O)H or -N(R # )-C(O)-(R # ) is an "acylamino" group, and each R # are independently defined above.

[0034] A "sulfonylamino" group is a group of the formula: -NHSO(R # ) or -N(alkyl)SO2(R # ) groups, where each alkyl and R # is defined above.

[0035] A "urea" group is a group of the formula: -N(alkyl)C(O)N(R # )2, -N(alkyl)C(O)NH(R # ), -N(alkyl)C(O)NH2, -NHC(O)N(R # )2, -NHC(O)NH(R # ) or —NH(CO)NH2, where each alkyl and R # are independently as defined above.

[0036] When groups described herein (with the exception of alkyl groups) are described as "substituted," they can be substituted with any suitable substituent(s). Illustrative examples of substituents include those found in the exemplary compounds and embodiments disclosed herein, as well as halogen (chloro, iodo, bromo, or fluoro), alkyl, hydroxyl, alkoxy, alkoxyalkyl, amino, alkylamino, carboxy, nitro, cyano, thiol, thioether, imine, imide, amidine, guanidine, enamine, aminocarbonyl, acylamino, phosphonate, phosphine, thiocarbonyl, sulfinyl, sulfone, sulfonamide, ketone, aldehyde, ester, urea, urethane, oxime, hydroxylamine, alkoxyamine, aralkoxyamine, N-oxide, hydrazine, hydrazide, hydrazone, azide, isocyanate, isothiocyanate, cyanate, thiocyanate, oxygen (=O), B(OH), O(alkyl)aminocarbonyl, monocyclic or fused or fused rings. Examples include cycloalkyl, which may be a single ring or multiple rings, fused or non-fused (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl); heterocyclyl, which may be a single ring or multiple rings, fused or non-fused (e.g., pyrrolidyl, piperidyl, piperazinyl, morpholinyl, or thiazinyl); aryl or heteroaryl, which may be a single ring or multiple rings, fused or non-fused (e.g., phenyl, naphthyl, pyrrolyl, indolyl, furanyl, thiophenyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, triazolyl, tetrazolyl, pyrazolyl, pyridyl, quinolinyl, isoquinolinyl, acridinyl, pyrazinyl, pyridazinyl, pyrimidyl, benzimidazolyl, benzothiophenyl, or benzofuranyl); aryloxy, aralkyloxy, heterocyclyloxy, and heterocyclylalkoxy.

[0037] As used herein, the term "piperidinedione compound" refers to compounds of Formula (I) and further embodiments provided herein. In one embodiment, a "piperidinedione compound" is a compound set forth in Table 1. The term "piperidinedione compound" includes pharmaceutically acceptable salts, tautomers, isotopic substitutions, and stereoisomers of the compounds provided herein.

[0038] As used herein, "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic acids or bases, including inorganic and organic acids and bases. Suitable pharmaceutically acceptable base addition salts of compounds of Formula (I) include, but are not limited to, metallic salts made from aluminum, calcium, lithium, magnesium, potassium, sodium, and zinc, or organic salts made from lysine, N,N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N-methyl-glucamine), and procaine. Suitable non-toxic acids include, but are not limited to, inorganic and organic acids such as acetic acid, alginic acid, anthranilic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, formic acid, fumaric acid, furoic acid, galacturonic acid, gluconic acid, glucuronic acid, glutamic acid, glycolic acid, hydrobromic acid, hydrochloric acid, isethionic acid, lactic acid, maleic acid, malic acid, mandelic acid, methanesulfonic acid, mucic acid, nitric acid, pamoic acid, pantothenic acid, phenylacetic acid, phosphoric acid, propionic acid, salicylic acid, stearic acid, succinic acid, sulfanilic acid, sulfuric acid, tartaric acid, and p-toluenesulfonic acid. Specific non-toxic acids include hydrochloric acid, hydrobromic acid, maleic acid, phosphoric acid, sulfuric acid, and methanesulfonic acid. Accordingly, specific examples of salts include formic acid hydrochloride and mesylate. Others are well known in the art, see, e.g., Remington's Pharmaceutical Sciences, 18th eds., Mack Publishing, Easton PA (1990) or Remington: The Science and Practice of Pharmacy, 19th eds., Mack Publishing, Easton PA (1995).

[0039] As used herein, unless otherwise indicated, the term "stereoisomer" or "stereoisomerically pure" refers to one stereoisomer of a piperidinedione compound that is substantially free of other stereoisomers of that compound. For example, a stereoisomerically pure compound having one chiral center is substantially free of the opposite enantiomer of that compound. A stereoisomerically pure compound having two chiral centers is substantially free of other diastereomers of that compound. A typical stereoisomerically pure compound contains more than about 80% by weight of one stereoisomer of the compound and less than about 20% by weight of other stereoisomers of the compound, more than about 90% by weight of one stereoisomer of the compound and less than about 10% by weight of other stereoisomers of the compound, more than about 95% by weight of one stereoisomer of the compound and less than about 5% by weight of other stereoisomers of the compound, or more than about 97% by weight of one stereoisomer of the compound and less than about 3% by weight of other stereoisomers of the compound. The piperidinedione compounds may have chiral centers and may exist as racemates, individual enantiomers or diastereomers, and mixtures thereof. All such isomeric forms, including mixtures thereof, are included in the embodiments disclosed herein.

[0040] The use of stereomerically pure forms of such piperidinedione compounds, as well as mixtures of these forms, are encompassed by the embodiments disclosed herein. For example, mixtures containing equal or unequal amounts of the enantiomers of a particular piperidinedione compound can be used in the methods and compositions disclosed herein. These isomers can be asymmetrically synthesized or resolved using standard techniques, such as chiral columns or chiral resolving agents. For example, Jacques, J., et al., Enantiomers, Racemates and Resolutions (Wiley-Interscience, New York, 1981); Wilen, SH, et al., Tetrahedron 33:2725 (1977); Eliel, EL, Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); Wilen, SH, Tables of Resolving Agents and Optical Resolutions p.268(ELEliel,Ed.,Univ.of Notre Dame Press,Notre Dame,IN,1972);Synthetic Methods(Wiley-VCH Verlag GmbH&Co.KGaA,Weinheim,Germany,2014);Toda,F.,Enantiomer Separation:Fundamentals and Practical Methods(Springer Science&Business Media,2007);Subramanian,G.Chiral Separation Techniques:A Practical See, for example, Ahuja, S., Chiral Separation Methods for Pharmaceutical and Biotechnological Products (John Wiley & Sons, 2011).

[0041] It should also be noted that the piperidinedione compounds may include E and Z isomers or mixtures thereof, as well as cis and trans isomers or mixtures thereof. In certain embodiments, the piperidinedione compounds are isolated as either the E or Z isomer. In other embodiments, the piperidinedione compounds are a mixture of E and Z isomers.

[0042] "Tautomers" refer to isomeric forms of a compound that are in equilibrium with each other. The concentrations of isomeric forms depend on the environment in which the compound is found, and can vary depending on, for example, whether the compound is a solid or in an organic or aqueous solution. For example, in aqueous solution, pyrazole exists in the following isomeric forms: [ka] which are called tautomers of each other.

[0043] As will be readily understood by those skilled in the art, a wide variety of functional groups and other structures may exhibit tautomerism, and all tautomers of the compounds of formula (I) are within the scope of the invention.

[0044] It is also noted that the piperidinedione compounds may contain unnatural proportions of atomic isotopes at one or more atoms. For example, the compounds may contain, for example, tritium ( 3 H), iodine-125( 125 I), sulfur 35( 35 S) or carbon 14 ( 14 It can be radiolabeled with a radioisotope such as deuterium ( 2 H), carbon-13 ( 13 C) or nitrogen-15( 15The compound may be enriched in an isotope, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 112, 113, 120, 121, 132, 143, 144, 150, 165, 170, 171, 182, 192, 193, 194, 195, 196, 197, 198, 199, As used herein, "deuterated" means that at least one hydrogen (H) is replaced with a deuterium (D or 2 H), meaning that the compound is enriched with deuterium at at least one position.

[0045] It is understood that each piperidinedione compound referred to herein can be provided in the form of any pharmaceutically acceptable salt discussed herein, regardless of stereoisomeric or isotopic composition.Similarly, it is understood that the isotopic composition can vary independently of the stereoisomeric composition of each piperidinedione compound referred to herein.Furthermore, the isotopic composition is limited to the elements present in each piperidinedione compound or its salt, but can vary independently of the choice of a pharmaceutically acceptable salt of each piperidinedione compound.

[0046] It should be noted that where there is a discrepancy between a depicted structure and the name for that structure, the depicted structure shall prevail.

[0047] The term "subject" or "patient" refers to animals, including, but not limited to, mammals, including primates (e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, rats, or mice. The terms "subject" and "patient" are used interchangeably herein in reference to a mammalian subject, such as a human subject.

[0048] As used herein, the term "androgen receptor" or "AR" or "NR3C4" refers to a nuclear hormone receptor that is activated by the binding of androgen hormones, including testosterone or dihydrotestosterone. The term "androgen receptor" can refer to the nucleotide sequence or protein sequence of the human androgen receptor (e.g., Entrez 367, Uniprot P10275, RefSeq NM_000044, or RefSeq NP_000035).

[0049] As used herein, the term "full-length AR" (AR-FL) refers to an AR protein containing all four functional domains, including the N-terminal transactivation domain (NTD, exon 1), the DNA-binding domain (DBD, exons 2-3), the hinge domain (exon 4), and the C-terminal ligand-binding domain (LBD, exons 4-8).

[0050] The term "castration-resistant prostate cancer" (CRPC) refers to advanced prostate cancer that worsens or progresses while a patient is undergoing androgen deprivation therapy or other therapies that lower testosterone, or prostate cancer that is considered hormone-refractory, hormone-naive, androgen-independent, or resistant to chemical or surgical castration. Castration-resistant prostate cancer (CRPC) is advanced prostate cancer that develops despite ongoing ADT and / or surgical castration. Castration-resistant prostate cancer is characterized by a history of surgical castration, treatment with gonadotropin-releasing hormone agonists (e.g., leuprolide) or antagonists (e.g., degarelix or abarelix), antiandrogens (e.g., bicalutamide, flutamide, enzalutamide, ketoconazole, aminoglutethamide), chemotherapy (e.g., docetaxel, paclitaxel, cabazitaxel, adriamycin, mitoxantrone, estramustine, cyclophosphamide), kinase inhibitors (imatinib (Gleevec®) or gefitinib (Iressa®), cabozantinib), or other anticancer drugs. It is defined as prostate cancer that continues to progress or worsen or continues to adversely affect the patient's health despite continued treatment with nib (Cometriq®, also known as XL184)) or other prostate cancer therapies (e.g., vaccines (sipuleucel-T (Provenge®), GVAX, etc.), herbs (PC-SPES) and lyase inhibitors (abiraterone)), as evidenced by increased or rising serum levels of prostate-specific antigen (PSA), metastasis, bone metastasis, pain, lymph node metastasis, increase in size of tumor growth or serum markers, worsening of prognostic markers or patient condition.

[0051] As used herein, unless otherwise specified, the phrase "unit dose" refers to a physically discrete unit of formulation appropriate for the subject to be treated (e.g., for a single dose). Each unit contains a predetermined amount of an active agent selected to produce a desired therapeutic effect (it being understood that multiple doses may be necessary to achieve the desired or optimal effect), optionally together with a pharmaceutically acceptable carrier (which may be provided in a predetermined amount). A unit dose may be, for example, a liquid (e.g., an acceptable carrier) containing a predetermined amount of one or more therapeutic agents, a predetermined amount of one or more therapeutic agents in solid form, a sustained-release formulation or drug delivery device containing a predetermined amount of one or more therapeutic agents, etc. It will be understood that a unit dose may contain various components in addition to the therapeutic agents. For example, acceptable carriers (e.g., pharmaceutically acceptable carriers), diluents, stabilizers, buffers, preservatives, etc., may be included, as described below. However, it will be understood that the total daily usage of the formulations of the present disclosure will be determined by the attending physician within the scope of sound medical judgment. The specific effective dosage level for a particular subject or organism will vary depending on a variety of factors, including the disease being treated and its severity, the activity of the specific active compound used, the particular composition used, the age, weight, general health, sex and diet of the subject, the time of administration, the excretion rate of the specific active compound used, the duration of treatment, drugs and / or additional therapies used in combination with or simultaneously with the specific compound used, and similar factors well known in the medical arts.

[0052] A "pharmaceutically acceptable excipient" refers to a substance that aids in the administration of an active agent to a subject, for example, by modifying the stability of the active agent or by modifying its absorption by the subject upon administration. Pharmaceutically acceptable excipients typically do not cause significant adverse toxicological effects to patients. Examples of pharmaceutically acceptable excipients include, for example, water, NaCl (including saline), normal saline, half-normal saline, sucrose, glucose, bulking agents, buffers, binders, fillers, disintegrants, lubricants, coating agents, sweeteners, flavorings, alcohol, oils, gelatin, carbohydrates such as amylose or starch, fatty acid esters, hydroxymethylcellulose, polyvinylpyrrolidine, coloring agents, and the like. Those skilled in the art will recognize that other pharmaceutical excipients known in the art are useful in the present invention, including, for example, those listed in Handbook of Pharmaceutical Excipients, Rowe RC, Shesky PJ, and Quinn ME, 6th Ed., The Pharmaceutical Press, RPS Publishing (2009). The terms "bulking agent" and "buffering agent" are used in accordance with their clear and ordinary meaning within the art.

[0053] As used herein, unless otherwise specified, the term "about," when used in reference to a dose, amount, or weight percent of a component of a composition or dosage form, means a dose, amount, or weight percent that would be recognized by one of ordinary skill in the art as providing an equivalent pharmacological effect to that obtained from the specified dose, amount, or weight percent. Specifically, the term "about" is meant to encompass doses, amounts, or weight percents within 30%, 25%, 20%, 15%, 10%, or 5% of the specified dose, amount, or weight percent.

[0054] As used herein, "administering" or "administration" refers to the act of physically delivering a substance present outside the body to a subject. Administration includes all forms known in the art to deliver therapeutic agents, including, but not limited to, topical, mucosal, injection, intradermal, intravenous, intramuscular delivery, or other physical delivery methods described herein or known in the art (e.g., implantation of a sustained release device such as a mini-osmotic pump into a subject, liposomal formulation, buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, intraarteriole, intraperitoneal, intraventricular, intracranial, or transdermal).

[0055] "Co-administered" means that a compound, composition, or agent described herein is administered simultaneously with, immediately before, or immediately after the administration of one or more additional compounds, compositions, or agents, including, for example, anti-cancer agents. Co-administration is intended to include simultaneous or sequential administration of compounds, compositions, or agents, individually or in combination (two or more compounds or agents). Co-administration includes administration of two compounds, compositions, or agents simultaneously or nearly simultaneously (e.g., within about 1, 5, 10, 15, 20, or 30 minutes) or sequentially in any order. Thus, co-administration can include administration of one active agent (e.g., a compound described herein) 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, or 24 hours before the administration of a second active agent. Co-administration can also be achieved by co-formulation, e.g., preparing a single dosage form containing both active agents. The active agents can be formulated separately. In such cases, the active agents are mixed together in the final dosage unit. Alternatively, co-administration as described herein can involve administering two separate unit dosage forms of at least two separate active agents (e.g., a piperidinedione compound and a second active agent described herein).

[0056] As used herein, the term "daily" is intended to mean that a therapeutic compound, such as a piperidinedione compound, is administered once or more than once daily for a period of time. The term "continuous" is intended to mean that a therapeutic compound, such as a piperidinedione compound, is administered daily for an uninterrupted period of at least 10 days to 52 weeks. As used herein, the terms "intermittent" or "intermittently" are intended to mean stopping and starting at regular or irregular intervals. For example, intermittent administration of a piperidinedione compound can be administration for 1 to 6 days per week, administration in cycles (e.g., daily administration for 1 to 10 consecutive days of a 28-day cycle, followed by a rest period without administration for the remainder of the 28-day cycle, or daily administration for 2 to 8 consecutive weeks, followed by a rest period without administration for up to 1 week), or administration every other day. As used herein, the term "cycle" is intended to mean that a therapeutic compound, such as a piperidinedione compound, is administered daily or continuously, separated by rest periods.

[0057] "Cycle therapy" refers to a regimen or therapy that includes dosing periods as described herein and rest periods as described herein.

[0058] As used herein, the term "administration period" refers to the period during which a subject is continuously or actively administered a compound or composition described herein.

[0059] As used herein, the term "drug holiday" often refers to a period of time following an administration period during which a subject is not administered a compound or composition described herein (e.g., a cessation of treatment). In certain embodiments, a "drug holiday" refers to a period during which a subject is not administered a single agent or during which treatment using a particular compound is discontinued. In such embodiments, a second therapeutic agent (e.g., an agent different from the compound or composition administered during the previous administration period) can be administered to the subject.

[0060] An "effective amount" is an amount sufficient to achieve the effect for which it is administered (e.g., treat a disease or alleviate one or more symptoms of a disease or condition). Thus, administration of an "amount" of a compound described herein to a subject refers to administration of an "effective amount" to achieve the desired therapeutic result. Therefore, for purposes of this specification, a "therapeutically effective amount" of a compound described herein is determined by considerations known in the art. The term "therapeutically effective amount" of a composition described herein refers to an amount of the composition that, when administered, is sufficient to treat one or more symptoms of a disease described herein. The administration of a compound described herein can be determined depending on factors such as the individual's medical condition, age, sex, and weight. A therapeutically effective amount also refers to an amount in which any toxic or adverse effects of the piperidinedione compound are outweighed by the therapeutically beneficial effects.

[0061] As used herein, "maintenance therapy" refers to treatment given to a disease after remission or best response has been achieved to prevent or delay recurrence. Maintenance therapy may include chemotherapy, hormone therapy, or targeted therapy.

[0062] "Remission," as used herein, is the reduction or elimination of signs and symptoms of cancer, such as multiple myeloma. In a partial remission, some, but not all, signs and symptoms of cancer have disappeared. In a complete remission, all signs and symptoms of cancer have disappeared, although the cancer may still be present in the body.

[0063] "Relapse" refers to the situation in which leukemia cells return to the bone marrow and normal blood cells decrease in patients whose leukemia has gone into remission after treatment.

[0064] The term "refractory or resistant" refers to the situation where leukemia cells persist in a patient's bone marrow even after intensive treatment.

[0065] The term "drug resistance" refers to a state in which a disease does not respond to treatment with a particular drug. Drug resistance can be intrinsic, meaning that the disease has never responded to a particular drug, or it can be acquired, meaning that the disease no longer responds to a particular drug that it previously responded to. In certain embodiments, drug resistance is intrinsic. In certain embodiments, drug resistance is acquired.

[0066] compound As used herein, the following formula (I): [ka] (In the formula, R N is H, Each R 1 are independently halogen, CN and C 1~3 alkyl, R 2 and R 3 are each independently H and C 1~3 alkyl, or R 2 and R 3 and the carbon to which they are attached are substituted or unsubstituted C 3~6 forming a cycloalkyl, Each R 4 are independently substituted or unsubstituted C 1~3 alkyl or two R 4 The groups, together with the same carbon atom or adjacent carbon atoms to which they are attached, may form a substituted or unsubstituted C 3~6 Form a cycloalkyl or two R 4 groups, taken together with the non-adjacent carbon atoms to which they are attached, form a substituted or unsubstituted 4- to 7-membered heterocyclyl; X is N, L is -O(C 1~6 alkyl)- or -(C 1~9 alkyl)-, n is 0 to 4, m is 0 to 8; V is [ka] where: A is N, CH or CR A and B is N, CH or CR B and Each R A are independently halogen, substituted or unsubstituted C 1~6 Alkyl and substituted or unsubstituted C 3~6 cycloalkyl; Each R B are independently halogen and substituted or unsubstituted C 1~6 alkyl, R C is a halogen or CF3, R 5 and R 6 is C 1~3 alkyl or R 5 and R 6 together with the carbon atoms to which they are attached, form a substituted or unsubstituted C 3~6 forming a cycloalkyl or a 3- to 6-membered heterocyclyl; a is 0 to 3, and b is 0 to 2) or a pharmaceutically acceptable salt, tautomer, isotopic substitution or stereoisomer thereof.

[0067] As used herein, the following formula (I): [ka] (In the formula, R N is H, Each R 1 are independently halogen, CN and C 1~3 alkyl, R 2 and R 3 are each independently H and C 1~3 alkyl, or R 2 and R 3and the carbon to which they are attached are substituted or unsubstituted C 3~6 forming a cycloalkyl, Each R 4 are independently substituted or unsubstituted C 1~3 alkyl or two R 4 The groups, together with the same carbon atom or adjacent carbon atoms to which they are attached, may form a substituted or unsubstituted C 3~6 Form a cycloalkyl or two R 4 groups, taken together with the non-adjacent carbon atoms to which they are attached, form a substituted or unsubstituted 4- to 7-membered heterocyclyl; X is N, L is -O(CH2) p -or-(CH2) p - and n is 0 to 4, m is 0 to 8; p is 1 to 3; V is [ka] where: A is N, CH or CR A and B is N, CH or CR B and Each R A are independently halogen, substituted or unsubstituted C 1~6 Alkyl and substituted or unsubstituted C 3~6 cycloalkyl; Each R B are independently halogen and substituted or unsubstituted C 1~6 alkyl, R C is a halogen or CF3, R 5 and R 6 is C 1~3 alkyl or R 5 and R 6 together with the carbon atoms to which they are attached, form a substituted or unsubstituted C 3~5forming a cycloalkyl or a 3- to 5-membered heterocyclyl; a is 0 to 3, and b is 0 to 2) or a pharmaceutically acceptable salt, tautomer, isotopic substitution or stereoisomer thereof.

[0068] In one embodiment of the compound of formula (I), the compound is [ka] In another embodiment of the compound of formula (I), the compound is [ka] is.

[0069] In some embodiments of compounds of Formula (I), (IIa), and (IIb), each R 1 are independently halogen and C 1~3 In some embodiments of compounds of Formula (I), (IIa), and (IIb), each R 1 is independently selected from Cl, F, Br, CN, —CH, —CHCH, and isopropyl. 1 is independently selected from Cl, F, CN, and —CH. In some embodiments, each R 1 is independently selected from Cl, F and CN.

[0070] In some embodiments of the compounds of Formula (I), n is 0. In other embodiments, n is 1 or 2.

[0071] In some embodiments of the compound of Formula (I), the compound is [ka] is.

[0072] In other embodiments of the compound of formula (I), the compound is [ka] is.

[0073] In still other embodiments of the compounds of Formula (I), the compound is [ka] is.

[0074] In some embodiments, the compound is a compound of formula (III), (IV), or (V), wherein each R 1 is independently selected from Cl, F, CN, and CH. In some such embodiments, the compound is of formula (III), (IV), or (V), and R 1 is F or Cl. In some embodiments of compounds of Formula (III), R 1 is F, Cl, or CN. In some embodiments of the compound of Formula (IV), R 1 is F.

[0075] In some embodiments of the compounds of Formula (I), R 2 and R 3 are each independently selected from H, substituted or unsubstituted methyl and ethyl, or R 2 and R 3 and the carbon to which they are attached form a substituted or unsubstituted cyclopropyl, cyclobutyl, or cyclopentyl. In some such embodiments, R 2 and R 3 are each independently selected from H and methyl, or R 2 and R 3 and the carbon to which they are attached form an unsubstituted cyclopropyl. 2 and R 3 are both H or methyl, or R 2 and R 3 and the carbon to which they are attached form an unsubstituted cyclopropyl. In some embodiments, R 2 and R 3 is H.

[0076] In some embodiments of the compounds of Formula (I), each R 4 are independently selected from substituted or unsubstituted methyl and ethyl, or two R 4 The groups, taken together with the same carbon atom to which they are attached, form a substituted or unsubstituted cyclopropyl or cyclobutyl. 4 are independently substituted or unsubstituted methyl, or two R 4 In yet another embodiment, the R groups, taken together with the same carbon atom to which they are attached, form an unsubstituted cyclopropyl. 4 are independently selected from methyl, CF3 and CH2OH, or two R 4 In yet another embodiment, R 4 is methyl. In some embodiments, R 4 is ethyl.

[0077] In some embodiments of the compounds of Formula (I), m is 0, 1, 2, 3, or 4. In some embodiments, m is 0, 1, or 2.

[0078] In some embodiments of the compounds of Formula (I), two R 4 In some such embodiments, the compounds are: [ka] is.

[0079] In some such embodiments, the compound is [ka] is.

[0080] In some such embodiments, the compound is [ka] is.

[0081] In some embodiments of the compounds of formula (I), (IIa), (IIb), (III), (IV), (V), (VI), (VII), (VIII), (IX) and (X), exemplary L groups include, but are not limited to, -O(CH2)(CH2)-, -O(CH2)(CH(CH3))-, -O(CH2)(C(CH3)2)-, -O(CH(CH3))(CH2)-, -O(C(CH3)2)(CH2)-, -O(CH(CH3))(CH(CH3))-, -O(CH(CH3))(C(CH3)2)-, -O(C(CH3)2)(CH(CH3))-, -(CH2)-, -(CH2)(CH2)-, -(CH2)(CH2)(CH2)-, -(C(CH3)2)(C(CH3)2)-, -(CH(CH3))-, -(C(CH3)2)-, -(CH(CH3))(CH(CH3))-, -(CH(CH3))(C(CH3)2)-, -(C(CH3)2)(CH(CH3))-, -(C(CH3)2)(C(CH3)2)-, -(CH3)(CH3)(CH(CH3))-, -(CH2)(CH(CH3))(CH2)-, -(CH(CH3))(CH2)(CH2)-, -(CH2)(CH2)(C(CH2)2)-, -(CH2)(C(CH2)2)(CH2)-, -(C(CH2)2)(CH2)(CH2)-, -(CH2)(CH(CH3))(CH(CH3))-, -(CH(CH3))(CH(CH3))(CH(CH3))-, -(CH(CH3))(CH(CH3))(CH2)-, -(CH(CH3))(CH2)(CH(CH3))-, -(CH2)(CH(CH3))(C(CH3)2)-, -(CH(CH3))(CH2)(C(CH2)2)-, -(C(CH3)2)(CH2)(C(CH3)2)-, -(CH2)(C(CH3)2)(C(CH3)2)-, -(CH2)(C(CH3)2)(CH(CH3))-, -(CH(CH3)(C(CH3)2)(CH2)-, -(C(CH3)2)(CH2)(CH(CH3))-, -(C(CH3)2)(CH(CH3))(CH2)-, -(C(CH3)2)(C(CH3)2)(CH2)-, -(CH(CH3))(CH(CH3))(C(CH3)2)-, -(CH(CH3))(C(CH3)2)(C(CH3)2)-, -(C(CH3)2)(CH(CH3))(C(CH3)2)-,-(CH(CH3))(C(CH3)2)(CH(CH3))-, -(C(CH3)2)(C(CH3)2)(CH(CH3))-, -(C(CH3)2)(CH(CH3))(CH(CH3))- and -(C(CH3)2)(C(CH3)2)(C(CH3)2)-. ,

[0082] In some embodiments of a compound of Formula (I), L is -O(CH2)(CH2)-, -O(CH2)(CH(CH3))-, -O(CH2)(C(CH3)2)-, -O(CH(CH3))(CH2)-, O(CH(CH3))(CH(CH3))-, -O(CH(CH3))(C(CH3)2)-, -O(C(CH3)2)(CH2)-, -(CH2)-, -(CH2)(CH2)-, or -(CH2)(CH2)(CH2)(CH2)-. In some embodiments of a compound of Formula (I), L is -O(CH2)( In some embodiments of the compound of Formula (I), L is -O(CH)(CH)-, -O(CH)(CH(CH))-, -O(CH)(CH(CH))-, -O(CH(CH))(CH)-, or -(CH)(CH)(CH)(CH)-. In other embodiments, L is -O(CH)(CH)- or -(CH)(CH)(CH)(CH)-. In still other embodiments, L is -O(CH)(CH)-. In some embodiments of the compound of Formula (I), L is -O(CH)(CH)-, -O(CH)(CH(CH))-, -O(CH(CH))(CH)-, or -(CH)(CH)(CH)(CH)-.

[0083] In some embodiments of the compounds of Formula (I), A is CH. In some embodiments of the compounds of Formula (I), B is CH. In some other embodiments, B is N.

[0084] In some embodiments of the compounds of Formula (I), a is 0, 1, or 2.

[0085] In some embodiments of the compounds of Formula (I), each R Ais independently selected from Cl, Br, F, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, CH2CH2CH(CH3)2, CH(CH3)CH(CH3), CF3, CF(CH3), CF2CH3, CH2CH2F, CH2CHF2, CH2CF3, CH2OH, CH(CH3)OH, CH2CH2OH, CH(CH3)CH2OH, CH2CH(CH3)OH, cyclopropyl, cyclobutyl, and cyclopentyl. In some such embodiments, each R A are independently selected from Cl, Br, F, methyl, ethyl, n-propyl, isopropyl, isobutyl, sec-butyl, CF, CFCH, CHCHF, CHCHF, CHOH, CH(CH)OH, cyclopropyl, cyclobutyl, and cyclopentyl. In some embodiments, when B is CH, each R A are independently selected from Cl, Br, F, methyl, ethyl, n-propyl, isopropyl, isobutyl, sec-butyl, CF, CFCH, CHCHF, CHCHF, cyclopropyl, cyclobutyl, and cyclopentyl. In other embodiments, when B is N, each R A is independently selected from Cl, F, methyl, ethyl, n-propyl, isopropyl, sec-butyl, CF2CH3, CH2CH2F, CH2CHF2, CH2OH, CH(CH3)OH, cyclopropyl, and cyclobutyl. In some such embodiments, each R A is independently selected from ethyl, isopropyl, and cyclopropyl.

[0086] In some embodiments of the compounds of Formula (I), b is 0 or 1. In some embodiments of the compounds of Formula (I), R B is methyl. In some embodiments of the compounds of Formula (I), R C is CF3 or Cl.

[0087] In some embodiments of the compounds of Formula (I), R 5 and R 6 is methyl or R 5and R 6 together with the carbon atom to which they are attached form cyclopropyl, cyclobutyl, tetrahydrofuranyl, or tetrahydropyranyl. In some embodiments, R 5 and R 6 is methyl or R 5 and R 6 together with the carbon atom to which they are attached form cyclobutyl or tetrahydrofuranyl. 5 and R 6 is methyl or R 5 and R 6 together with the carbon atom to which they are attached form cyclobutyl, cyclopentyl, cyclohexyl, or tetrahydrofuranyl.

[0088] In some embodiments of compounds of Formula (III), (IV), or (V), each R 1 are independently selected from Cl, F, CN, and CH; R 2 and R 3 is H. In some such embodiments, each R 4 are independently selected from methyl, CF3 and CH2OH, or two R 4 In some such embodiments, R 4 is methyl. In some such embodiments, R 4 is ethyl. In some other such embodiments, L is -O(CH2)(CH2)- or -(CH2)(CH2)(CH2)-. In some other such embodiments, L is -O(CH2)(CH(CH3))-, -O(CH(CH3))(CH2)-. In still other such embodiments, A is CH. In still other such embodiments, B is CH and each R Ais independently selected from Cl, Br, F, methyl, ethyl, n-propyl, isopropyl, isobutyl, sec-butyl, CF, CFCH, CHCHF, CHCHF, cyclopropyl, cyclobutyl, and cyclopentyl. In other such embodiments, B is N and each R A is independently selected from Cl, F, methyl, ethyl, n-propyl, isopropyl, sec-butyl, CF2CH3, CH2CH2F, CH2CHF2, CH2OH, CH(CH3)OH, and cyclopropyl. In some other such embodiments, each R A is ethyl, isopropyl, or cyclopropyl. In still other such embodiments, R 5 and R 6 is methyl or R 5 and R 6 together with the carbon atom to which they are attached form cyclobutyl or tetrahydrofuranyl. 5 and R 6 is methyl or R 5 and R 6 together with the carbon atom to which they are attached form cyclobutyl, cyclopentyl, cyclohexyl, or tetrahydrofuranyl.

[0089] In some embodiments of compounds of Formula (I), (IIa) and (IIb), R N is H, Each R 1 is independently selected from Cl, F, Br, CN, —CH3, —CH2CH3, and isopropyl; R 2 and R 3 are each independently selected from H, substituted or unsubstituted methyl and ethyl, or R 2 and R 3 and the carbon to which they are attached form a substituted or unsubstituted cyclopropyl, cyclobutyl, or cyclopentyl; Each R 4are independently selected from substituted or unsubstituted methyl or ethyl, or two R 4 groups, taken together with the same carbon atom or adjacent carbon atoms to which they are attached, form a substituted or unsubstituted cyclopropyl or cyclobutyl, or two R 4 groups, taken together with the non-adjacent carbon atoms to which they are attached, form a substituted or unsubstituted 4- to 7-membered heterocyclyl; X is N, L is -O(C 1~5 alkyl)- or -(C 1~5 alkyl)-, n is 0 to 4, m is 0 to 2; V is [ka] where: A is N, CH or CR A and B is N, CH or CR B and Each R A is independently selected from Cl, Br, F, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, CH2CH2CH(CH3)2, CH(CH3)CH(CH3)2, CF3, CF2CH3, CH2CH2F, CH2CHF2, CH2CF3, CH2OH, CH(CH3)OH, CH2CH2OH, CH(CH3)CH2OH, CH2CH(CH3)OH, cyclopropyl, cyclobutyl and cyclopentyl; Each R B is independently selected from halogen and methyl; R C is a halogen or CF3, R 5 and R 6 is methyl or R 5 and R 6together with the carbon atom to which they are attached form a substituted or unsubstituted cyclobutyl, cyclopentyl, cyclohexyl, or tetrahydrofuranyl; a is 0 to 3, and b is 0 to 2.

[0090] In some embodiments of compounds of Formula (I), (IIa) and (IIb), R N is H, Each R 1 is independently selected from Cl, F, Br, CN, —CH3, —CH2CH3, and isopropyl; R 2 and R 3 are each independently selected from H, substituted or unsubstituted methyl and ethyl, or R 2 and R 3 and the carbon to which they are attached form a substituted or unsubstituted cyclopropyl, cyclobutyl, or cyclopentyl; Each R 4 are independently selected from substituted or unsubstituted methyl or ethyl, or two R 4 groups, taken together with the same carbon atom or adjacent carbon atoms to which they are attached, form a substituted or unsubstituted cyclopropyl or cyclobutyl, or two R 4 groups, taken together with the non-adjacent carbon atoms to which they are attached, form a substituted or unsubstituted 4- to 7-membered heterocyclyl; X is N, L is -O(CH2) p -or-(CH2) p - and n is 0 to 4, m is 0 to 2; p is 1 to 3; V is [ka] where: A is N, CH or CR A and B is N, CH or CR B and Each R A is independently selected from Cl, Br, F, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, CH2CH2CH(CH3)2, CH(CH3)CH(CH3)2, CF3, CF2CH3, CH2CH2F, CH2CHF2, CH2CF3, CH2OH, CH(CH3)OH, CH2CH2OH, CH(CH3)CH2OH, CH2CH(CH3)OH, cyclopropyl, cyclobutyl and cyclopentyl; Each R B is independently selected from halogen and methyl; R C is a halogen or CF3, R 5 and R 6 is methyl or R 5 and R 6 together with the carbon atom to which they are attached form a substituted or unsubstituted cyclobutyl or tetrahydrofuranyl; a is 0 to 3, and b is 0 to 2.

[0091] In some embodiments of compounds of Formula (III), (IV), and (V), R N is H, Each R 1 is independently selected from Cl, F, Br, CN, —CH3, —CH2CH3, and isopropyl; R 2 and R 3 are each independently selected from H, substituted or unsubstituted methyl and ethyl, or R 2 and R 3 and the carbon to which they are attached form a substituted or unsubstituted cyclopropyl, cyclobutyl, or cyclopentyl; Each R 4 are independently selected from substituted or unsubstituted methyl or ethyl, or two R 4groups, taken together with the same carbon atom or adjacent carbon atoms to which they are attached, form a substituted or unsubstituted cyclopropyl or cyclobutyl, or two R 4 groups, taken together with the non-adjacent carbon atoms to which they are attached, form a substituted or unsubstituted 4- to 7-membered heterocyclyl; X is N, L is -O(C 1~5 alkyl)- or -(C 1~5 alkyl)-, n is 0 to 4, m is 0, 1 or 2; V is [ka] where: A is N, CH or CR A and B is N, CH or CR B and Each R A is independently selected from Cl, Br, F, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, CH2CH2CH(CH3)2, CH(CH3)CH(CH3)2, CF3, CF2CH3, CH2CH2F, CH2CHF2, CH2CF3, CH2OH, CH(CH3)OH, CH2CH2OH, CH(CH3)CH2OH, CH2CH(CH3)OH, cyclopropyl, cyclobutyl and cyclopentyl; Each R B is independently selected from halogen and methyl; R C is a halogen or CF3, R 5 and R 6 is methyl or R 5 and R 6 together with the carbon atom to which they are attached form a substituted or unsubstituted cyclobutyl, cyclopentyl, cyclohexyl, or tetrahydrofuranyl; a is 0 to 3, and b is 0 to 2.

[0092] In some embodiments of compounds of Formula (III), (IV), and (V), R N is H, Each R 1 is independently selected from Cl, F, Br, CN, —CH3, —CH2CH3, and isopropyl; R 2 and R 3 are each independently selected from H, substituted or unsubstituted methyl and ethyl, or R 2 and R 3 and the carbon to which they are attached form a substituted or unsubstituted cyclopropyl, cyclobutyl, or cyclopentyl; Each R 4 are independently selected from substituted or unsubstituted methyl or ethyl, or two R 4 groups, taken together with the same carbon atom or adjacent carbon atoms to which they are attached, form a substituted or unsubstituted cyclopropyl or cyclobutyl, or two R 4 groups, taken together with the non-adjacent carbon atoms to which they are attached, form a substituted or unsubstituted 4- to 7-membered heterocycle; X is N, L is -O(CH2) p -or-(CH2) p - and n is 0 to 4, m is 0, 1 or 2; p is 1 to 3; V is [ka] where: A is N, CH or CR A and B is N, CH or CR B and Each R Ais independently selected from Cl, Br, F, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, CH2CH2CH(CH3)2, CH(CH3)CH(CH3)2, CF3, CF2CH3, CH2CH2F, CH2CHF2, CH2CF3, CH2OH, CH(CH3)OH, CH2CH2OH, CH(CH3)CH2OH, CH2CH(CH3)OH, cyclopropyl, cyclobutyl and cyclopentyl; Each R B is independently selected from halogen and methyl; R C is a halogen or CF3, R 5 and R 6 is methyl or R 5 and R 6 together with the carbon atom to which they are attached form a substituted or unsubstituted cyclobutyl or tetrahydrofuranyl; a is 0 to 3, and b is 0 to 2.

[0093] Further embodiments provided herein include any combination of one or more of the specific embodiments described above.

[0094] In some embodiments of the compound of Formula (I), the compound is a compound from Table 1.

[0095] Representative compounds of formula (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX) or (X) are shown in Table 1.

[0096] [Table 1]

[0097] [Table 2]

[0098] Table 3

[0099] Table 4

[0100] Table 5

[0101] Table 6

[0102] Table 7

[0103] Table 8

[0104] Table 9

[0105] Table 10

[0106] Table 11

[0107] Table 12

[0108] Table 13

[0109] Table 14

[0110] Table 15

[0111] Table 16

[0112] Table 17

[0113] Table 18

[0114] Table 19

[0115] Table 20

[0116] Table 21

[0117] Table 22

[0118] Table 23

[0119] Table 24

[0120] Table 25

[0121] Table 26

[0122] Table 27

[0123] Table 28

[0124] Table 29

[0125] Table 30

[0126] Table 31

[0127] Table 32

[0128] Table 33

[0129] Table 34

[0130] Table 35

[0131] Table 36

[0132] Table 37

[0133] Table 38

[0134] Table 39

[0135] Table 40

[0136] Table 41

[0137] Table 42

[0138] Table 43

[0139] Table 44

[0140] Table 45

[0141] Table 46

[0142] Table 47

[0143] Table 48

[0144] Table 49

[0145] Table 50

[0146] Table 51

[0147] Table 52

[0148] Table 53

[0149] Table 54

[0150] Table 55

[0151] Table 56

[0152] Table 57

[0153] Table 58

[0154] Table 59

[0155] Table 60

[0156] Table 61

[0157] Table 62

[0158] Table 63

[0159] Table 64

[0160] Table 65

[0161] Table 66

[0162] Table 67

[0163] Table 68

[0164] Table 69

[0165] Table 70

[0166] Table 71

[0167] Table 72

[0168] Table 73

[0169] Table 74

[0170] Table 75

[0171] Table 76

[0172] Table 77

[0173] Table 78

[0174] Table 79

[0175] Table 80

[0176] Table 81

[0177] Table 82

[0178] Table 83

[0179] Table 84

[0180] Table 85

[0181] Table 86

[0182] Table 87

[0183] Table 88

[0184] Table 89

[0185] Table 90

[0186] Table 91

[0187] Table 92

[0188] Table 93

[0189] Table 94

[0190] Table 95

[0191] Table 96

[0192] Table 97

[0193] Table 98

[0194] Table 99

[0195] In certain embodiments, the compound is (S)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl) )-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl) -2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, acetamide and N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide or a pharmaceutically acceptable salt, tautomer or isotope thereof.

[0196] In one embodiment, the compound is 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof.

[0197] In one embodiment, the compound is 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide.

[0198] The piperidinedione compounds can be prepared according to the methods described in the examples provided herein or in U.S. Pat. No. 11,149,007, the disclosure of which is incorporated herein by reference in its entirety. The piperidinedione compounds can also be synthesized according to other methods apparent to those skilled in the art based on the teachings herein.

[0199] Second drug The second agent for use in the methods provided herein is selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor. In one embodiment, the second agent is selected from capivasertib, ipatasertib, AZD8186, 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, tazemetostat, ruxolitinib, and sorafenib.

[0200] How to use In one embodiment, provided herein are methods for treating, preventing, managing, and / or ameliorating an androgen receptor-mediated disease or one or more symptoms or causes thereof by administering a piperidinedione compound in combination with one or more second agents selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor to a patient having the disease or one or more symptoms or causes thereof. In one embodiment, provided herein are methods for treating, preventing, managing, and / or ameliorating an androgen receptor-mediated disease or one or more symptoms or causes thereof by administering a piperidinedione compound in combination with one or more second agents selected from capivasertib, ipatasertib, AZD8186, 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, tazemetostat, ruxolitinib, and sorafenib to a patient having the disease or one or more symptoms or causes thereof.

[0201] Provided herein are piperidinedione compounds for use in methods for treating, preventing, managing, and / or ameliorating an androgen receptor-mediated disease or one or more symptoms or causes thereof, wherein the compound is administered in combination with one or more second agents selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor. In one aspect, provided herein are piperidinedione compounds for use in methods for treating, preventing, managing, and / or ameliorating an androgen receptor-mediated disease or one or more symptoms or causes thereof, wherein the compound is administered in combination with one or more second agents selected from capivasertib, ipatasertib, AZD8186, 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, tazemetostat, ruxolitinib, and sorafenib.

[0202] In certain embodiments, the methods and / or combinations provided herein synergistically inhibit the proliferation of prostate cancer cells.

[0203] In one aspect, methods are provided herein for treating patients who have previously been treated for an androgen receptor-mediated disease but who do not respond to therapy, as well as for patients who have not previously been treated. Methods for treating patients regardless of their age are also included, although some diseases or disorders are more prevalent in certain age groups. Additionally, methods are included for treating patients who have undergone surgery to treat the disease or condition in question, as well as patients who have not undergone surgery. Because patients with androgen receptor-mediated diseases have heterogeneous clinical symptoms and differing clinical outcomes, the treatment administered to a patient may vary depending on the patient's prognosis. A skilled clinician will be able to easily determine, without undue experimentation, the specific secondary agents, types of surgery, and types of non-drug-based standard therapies that can be effectively used to treat individual patients with androgen receptor-mediated diseases.

[0204] In some embodiments, the method comprises the step of: (S)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, -thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide and N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(( R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, and a second agent selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor.

[0205] In some embodiments, the method comprises administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, and a second agent selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor.

[0206] In one embodiment, the method comprises administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide and a second agent selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor.

[0207] In some embodiments, the method comprises the step of: (S)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, )-2-ethylphenoxy)ethyl)-3-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2 -(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide and N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl) (4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl-2-methylpiperazin-1-yl)acetamide, or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, in combination with one or more second agents selected from capivasertib, ipatasertib, AZD8186, 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, tazemetostat, ruxolitinib, and sorafenib.

[0208] In some embodiments, the method comprises administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, and a second agent selected from capivasertib, ipatasertib, AZD8186, 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, tazemetostat, ruxolitinib, and sorafenib.

[0209] In one embodiment, the method comprises administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide and a second agent selected from capivasertib, ipatasertib, AZD8186, 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, tazemetostat, ruxolitinib, and sorafenib.

[0210] In certain embodiments, the methods provided herein comprise administering a piperidinedione compound in combination with capivasertib. ... -5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazine 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide and N-(3-chloro-5-(2, 6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, in combination with capivasertib.In some embodiments, the methods provided herein include administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, in combination with capivasertib. In some embodiments, the methods provided herein include administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide in combination with capivasertib.

[0211] In certain embodiments, the methods provided herein comprise administering a piperidinedione compound in combination with ipatasertib. ... -5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazine 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide and N-(3-chloro-5-(2, 6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, in combination with ipatasertib.In some embodiments, the methods provided herein include administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, in combination with ipatasertib. In some embodiments, the methods provided herein include administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide in combination with ipatasertib.

[0212] In certain embodiments, the methods provided herein include administering a piperidinedione compound in combination with AZD8186. ... -5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazine 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide and N-(3-chloro-5-(2, 6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, in combination with AZD8186.In some embodiments, the methods provided herein comprise administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, in combination with AZD8186. In some embodiments, the methods provided herein include administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide in combination with AZD8186.

[0213] In certain embodiments, the methods provided herein include administering a piperidinedione compound in combination with 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid. In certain embodiments, the methods provided herein include administering a piperidinedione compound in combination with 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid. In certain embodiments, the methods provided herein include administering a piperidinedione compound in combination with 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid. In certain embodiments, the methods provided herein include administering a piperidinedione compound in combination with 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid. 4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide and N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(( R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, in combination with 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid.In some embodiments, the methods provided herein comprise administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, in combination with 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid. In some embodiments, the methods provided herein include administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide in combination with 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid.

[0214] In certain embodiments, the methods provided herein comprise administering a piperidinedione compound in combination with tazemetostat. ... 5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazine- 1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide and N-(3-chloro-5-(2,6 or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, in combination with tazemetostat.In some embodiments, the methods provided herein comprise administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, or a pharmaceutically acceptable salt, tautomer, or isotopic substitute thereof, in combination with tazemetostat. In certain embodiments, the methods provided herein comprise administering a piperidinedione compound in combination with tazemetostat.

[0215] In certain embodiments, the methods provided herein comprise administering a piperidinedione compound in combination with ruxolitinib. ... -5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazine 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide and N-(3-chloro-5-(2, 6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, in combination with ruxolitinib.In some embodiments, the methods provided herein include administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, in combination with ruxolitinib. In some embodiments, the methods provided herein include administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide in combination with ruxolitinib.

[0216] In certain embodiments, the methods provided herein comprise administering a piperidinedione compound in combination with sorafenib. ... -5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazine 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide and N-(3-chloro-5-(2 ,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, in combination with sorafenib.In some embodiments, the methods provided herein comprise administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, or a pharmaceutically acceptable salt, tautomer, or isotopic substitution thereof, in combination with sorafenib. In some embodiments, the methods provided herein include administering 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide in combination with sorafenib.

[0217] In some embodiments, the AR-mediated disease is an AR wild-type mediated disease. In other embodiments, the AR-mediated disease is the result of AR amplification.

[0218] In certain embodiments, the AR-mediated disease is prostate cancer. In some such embodiments, the prostate cancer is castration-resistant prostate cancer (CRPC). In some such embodiments, the prostate cancer is metastatic castration-resistant prostate cancer (mCRPC). In yet other embodiments, the prostate cancer is non-metastatic CRPC (nmCRPC). In some embodiments, the prostate cancer is hormone-resistant. In some embodiments, the prostate cancer is resistant to treatment with an AR antagonist. For example, the prostate cancer is resistant to treatment with one or more of enzalutamide, bicalutamide, abiraterone, ARN-509, ODM-201, EPI-001, EPI-506, AZD-3514, galeterone, ASC-J9, flutamide, hydroxyflutamide, nilutamide, cyproterone acetate, ketoconazole, or spironolactone.

[0219] Provided herein is a method for reducing AR levels compared to baseline levels, comprising administering to a subject an effective amount of a piperidinedione compound in combination with one or more second agents selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor. Also provided herein is a piperidinedione compound for use in a method for reducing intracellular AR levels in vivo, ex vivo, or in vitro, comprising contacting cells with an effective amount of the piperidinedione compound in combination with one or more second agents selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor. In one embodiment, the cells are present in a patient's body. In one embodiment, the cells are not present in a patient's body. In one embodiment, provided herein is a method for reducing the level of wild-type AR in a tumor, comprising administering a therapeutically effective amount of a piperidinedione compound in combination with one or more second agents selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor, thereby reducing the level of wild-type AR in the tumor. In one embodiment, provided herein is a method for reducing the level of full-length AR (AR-FL) in a tumor, comprising administering a therapeutically effective amount of a piperidinedione compound in combination with one or more second agents selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor, thereby reducing the level of full-length AR (AR-FL) in the tumor. In some embodiments, the AR level is reduced compared to the AR level before administering the piperidinedione compound. In some embodiments, the AR level is reduced by 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99% compared to the AR level prior to administration of the piperidinedione compound in combination with one or more second agents selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor.

[0220] The dose of the piperidinedione compound administered to a subject varies widely and is left to the discretion of a medical professional. Generally, the piperidinedione compound may be administered at a dose of about 0.001 mg / kg to about 10 mg / kg of the subject's body weight, one to four times daily. However, this dosage may be appropriately modified depending on the subject's age, body weight, and medical condition, as well as the type of administration. In one embodiment, the dose is about 0.001 mg / kg to about 5 mg / kg of the subject's body weight, about 0.01 mg to about 5 mg / kg of the subject's body weight, about 0.05 mg to about 1 mg, about 0.1 mg to about 0.75 mg, or about 0.25 mg to about 0.5 mg / kg of the subject's body weight. In one embodiment, the piperidinedione compound is administered once daily. In either case, the amount of the piperidinedione compound administered depends on factors such as the solubility of the active ingredient, the formulation used, and the route of administration.

[0221] In another embodiment, provided herein is a method for treating or preventing an AR-mediated disease, comprising administering from about 0.01 mg / day to about 750 mg / day, from about 0.1 mg / day to about 375 mg / day, from about 0.1 mg / day to about 150 mg / day, from about 0.1 mg / day to about 75 mg / day, from about 0.1 mg / day to about 50 mg / day, from about 0.1 mg / day to about 25 mg / day, or from about 0.1 mg / day to about 10 mg / day of a piperidinedione compound to a subject having an AR-mediated disease.

[0222] The piperidinedione compounds may be administered once, twice, three times, four times, or more times daily, hi certain embodiments, doses of 100 mg or less are administered as a single daily dose, and doses of more than 100 mg are administered twice daily in an amount equal to half the total daily dose.

[0223] Pharmaceutical Compositions and Routes of Administration The piperidinedione compounds provided herein can be administered orally, topically, or parenterally to a subject in conventional forms of preparation (e.g., capsules, microcapsules, tablets, granules, powders, troches, pills, suppositories, injections, suspensions, syrups, patches, creams, lotions, ointments, gels, sprays, solutions, and emulsions).

[0224] The piperidinedione compounds can be administered orally, topically, or parenterally to a subject in conventional forms of preparation (e.g., capsules, microcapsules, tablets, granules, powders, troches, pills, suppositories, injections, suspensions, syrups, patches, creams, lotions, ointments, gels, sprays, solutions, and emulsions). Suitable formulations can be prepared using conventional organic or inorganic additives, such as excipients (e.g., sucrose, starch, mannitol, sorbitol, lactose, glucose, cellulose, talc, calcium phosphate, or calcium carbonate), binders (e.g., cellulose, methylcellulose, hydroxymethylcellulose, polypropylpyrrolidone, polyvinylpyrrolidone, gelatin, gum arabic, polyethylene glycol, sucrose, or starch), disintegrants (e.g., starch, carboxymethylcellulose, hydroxypropyl starch, low-substituted hydroxypropyl cellulose, sodium bicarbonate, calcium phosphate, or calcium citrate), The compositions can be prepared by a commonly used method using lubricants (e.g., magnesium stearate, light anhydrous silicic acid, talc, or sodium lauryl sulfate), flavoring agents (e.g., citric acid, menthol, glycine, or orange powder), preservatives (e.g., sodium benzoate, sodium sulfite, methylparaben, or propylparaben), stabilizers (e.g., citric acid, sodium citrate, or acetic acid), suspending agents (e.g., methylcellulose, polyvinylpyrrolidone, or aluminum stearate), dispersing agents (e.g., hydroxypropylmethylcellulose), diluents (e.g., water), and base waxes (e.g., cocoa butter, white petrolatum, or polyethylene glycol). The effective amount of the piperidinedione compound in the pharmaceutical composition can be a level that achieves the desired efficacy, for example, about 0.005 mg / kg to about 10 mg / kg of subject's body weight in a unit dose for both oral and parenteral administration.

[0225] In one embodiment, provided herein is a capsule comprising a piperidinedione compound and no additional carriers, excipients, or vehicles.

[0226] In another embodiment, provided herein are compositions comprising an effective amount of a piperidinedione compound and a pharmaceutically acceptable carrier or vehicle, wherein the pharmaceutically acceptable carrier or vehicle can comprise an excipient, diluent, or mixtures thereof. In one embodiment, the composition is a pharmaceutical composition.

[0227] The compositions can take the form of tablets, chewable tablets, capsules, solutions, parenteral solutions, troches, suppositories, suspensions, and the like. The compositions can be formulated to contain a daily dose or a convenient fraction of a daily dose in a dosage unit, which can be a single tablet or capsule or a convenient volume of liquid. In one embodiment, solutions are prepared from water-soluble salts (e.g., hydrochlorides). Generally, all compositions are prepared according to methods known in pharmaceutical chemistry. Capsules can be prepared by mixing the piperidinedione compound with a suitable carrier or diluent and filling the appropriate amount of the mixture into capsules. Typical carriers and diluents include, but are not limited to, inert powdered substances such as many different types of starch, powdered cellulose (e.g., crystalline and microcrystalline cellulose), sugars (e.g., fructose, mannitol, and sucrose, grain flours, and similar edible powders).

[0228] Tablets can be prepared by direct compression, wet granulation, or dry granulation. These formulations usually incorporate diluents, binders, lubricants, and disintegrants in addition to the compound. Typical diluents include, for example, various types of starch, lactose, mannitol, kaolin, calcium phosphate or sulfate, inorganic salts (e.g., sodium chloride), and powdered sugar. Powdered cellulose derivatives are also useful. Typical tablet binders are substances such as starch, gelatin, and sugars (e.g., lactose, fructose, glucose, etc.). Natural and synthetic gums are also convenient, including gum arabic, alginates, methylcellulose, polyvinylpyrrolidine, and the like. Polyethylene glycol, ethylcellulose, and waxes can also serve as binders.

[0229] Lubricants may be required in tablet formulations to prevent dyes from sticking to the tablet and punches. Lubricants can be selected from slippery solids such as talc, magnesium and calcium stearate, stearic acid, and hydrogenated vegetable oils. Tablet disintegrants are substances that expand when moistened, breaking up the tablet and releasing the compound. Tablet disintegrants include starch, clay, cellulose, algin, and gums. More specifically, for example, corn starch and potato starch, methylcellulose, agar, bentonite, wood cellulose, powdered sponge, cation exchange resins, alginic acid, guar gum, citrus pulp, and carboxymethylcellulose, and sodium lauryl sulfate can be used. Tablets can be coated with sugar as a flavoring and sealant, or with a film-forming protecting agent to modify the dissolution properties of the tablet. The composition can also be formulated as a chewable tablet by using substances such as mannitol in the formulation.

[0230] When it is desired to administer the piperidinedione compounds as a suppository, typical bases can be used. Cocoa butter is a conventional suppository base, which can be modified by adding waxes to slightly raise its melting point. Water-miscible suppository bases are widely used, especially those containing polyethylene glycols of various molecular weights.

[0231] The effect of the piperidinedione compound can be delayed or prolonged by appropriate formulation. For example, slowly dissolving pellets of the piperidinedione compound can be prepared and incorporated into tablets or capsules or as sustained-release implant devices. This technique also involves producing pellets with several different dissolution rates and filling capsules with a mixture of pellets. Tablets or capsules can be coated with a film that resists dissolution for a predictable period of time. Even parenteral preparations can be made long-acting by dissolving or suspending the piperidinedione compound in an oily vehicle or emulsifying vehicle that allows it to gradually disperse in serum.

[0232] In certain embodiments, the piperidinedione compound is administered orally. In one embodiment, when administered orally, the piperidinedione compound is administered with food and water. In another embodiment, the piperidinedione compound is dispersed in water or juice (e.g., apple juice or orange juice) or any other liquid and administered orally as a solution or suspension.

[0233] The piperidinedione compounds may also be administered intradermally, intramuscularly, intraperitoneally, transdermally, intravenously, subcutaneously, intranasally, epidurally, sublingually, intracerebrally, intravaginally, transdermally, rectally, mucosally, by inhalation, or topically to the ear, nose, eye, or skin. The mode of administration is left to the discretion of the healthcare professional, and may depend, in part, on the site of the medical condition.

[0234] In another embodiment, provided herein is a unit dose formulation comprising about 0.1 mg to 500 mg, about 1 mg to 250 mg, about 1 mg to about 100 mg, about 1 mg to about 50 mg, about 1 mg to about 25 mg, or about 1 mg to about 10 mg of a piperidinedione compound.

[0235] In certain embodiments, provided herein are unit dose formulations comprising about 0.1 mg or 100 mg of a piperidinedione compound.

[0236] In another embodiment, provided herein is a unit dose formulation comprising 0.5 mg, 1 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg, 35 mg, 50 mg, 70 mg, 100 mg, 125 mg, 140 mg, 175 mg, 200 mg, 250 mg, 280 mg, 350 mg, 500 mg, 560 mg, 700 mg, 750 mg, 1000 mg, or 1400 mg of a piperidinedione compound.

[0237] In certain embodiments, tazemetostat can be formulated into a suitable dosage unit with pharmaceutically acceptable excipients, carriers, adjuvants, and vehicles suitable for oral administration. In certain embodiments, tazemetostat is formulated as a tablet for oral administration. In one embodiment, tazemetostat is orally administered at a daily dose of 800 mg. In one embodiment, tazemetostat is orally administered at a dose of 400 mg twice a day.

[0238] In certain embodiments, ruxolitinib can be formulated into a suitable dosage unit with pharmaceutically acceptable excipients, carriers, adjuvants and vehicles suitable for oral administration. In certain embodiments, ruxolitinib is formulated as a tablet for oral administration. In one embodiment, ruxolitinib is orally administered at a dose of 5 mg, 10 mg, 15 mg, 20 mg or 25 mg. In one embodiment, ruxolitinib is orally administered at a dose of 5 mg, 10 mg, 15 mg, 20 mg or 25 mg twice a day.

[0239] In certain embodiments, sorafenib can be formulated into suitable dosage units with pharmaceutically acceptable excipients, carriers, adjuvants and vehicles suitable for oral administration.In certain embodiments, sorafenib is formulated as tablets for oral administration.In one embodiment, sorafenib is orally administered at a daily dose of 800mg.In one embodiment, sorafenib is orally administered at a dose of 400mg twice a day.

[0240] Combination therapy In one embodiment, provided herein are methods for treating, preventing, and / or managing an androgen receptor (AR)-mediated disease, comprising administering to a patient having an androgen receptor (AR)-mediated disease a piperidinedione compound in combination with one or more second agents selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor, optionally in combination with radiation therapy, blood transfusion, or surgery. In one embodiment, the second agent is selected from capivasertib, ipatasertib, AZD8186, 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, tazemetostat, ruxolitinib, and sorafenib.

[0241] As used herein, the term "in combination" includes the use of two or more therapies (e.g., one or more prophylactic and / or therapeutic agents). However, the use of the term "in combination" does not restrict the order in which therapies (e.g., prophylactic and / or therapeutic agents) are administered to a patient with a disease or disorder. For example, "in combination" can include administration as a mixture, simultaneous administration using separate formulations, and sequential administration in any order. "Sequentially" means that a specific amount of time has elapsed between the administration of active agents. For example, "sequentially" can mean that more than 10 minutes have elapsed between the administration of separate active agents. Here, the period of time can be more than 10 minutes, more than 30 minutes, more than 1 hour, more than 3 hours, more than 6 hours, or more than 12 hours. For example, a first therapy (e.g., a prophylactic or therapeutic agent, such as a formulation of Compound 1 provided herein) can be administered prior to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 ​​hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks before), concomitantly with, or subsequent to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 ​​hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks before) administration of a second therapy (e.g., a prophylactic or therapeutic agent) to a subject. Triple therapy is also contemplated herein.

[0242] In one embodiment, the piperidinedione compound provided herein and one or more second active agents can be administered to a patient simultaneously or sequentially by the same or different administration routes. In one embodiment, the piperidinedione compound provided herein and one or more second active agents can be administered to a patient simultaneously or sequentially by the same or different administration routes. The suitability of a particular administration route for a particular active agent will depend on the active agent itself (e.g., whether it can be administered orally without being decomposed before entering the bloodstream) and the androgen receptor (AR)-mediated disease being treated.

[0243] The route of administration of the piperidinedione compounds provided herein is independent of the route of administration of the second therapeutic agent. In one embodiment, the piperidinedione compounds provided herein and the second therapeutic agent are administered by the same mode of administration. In another embodiment, the piperidinedione compounds provided herein are administered by one mode of administration, while the second therapeutic agent is administered by a different mode of administration.

[0244] In some embodiments of the methods described herein, the methods further comprise administering one or more additional agents selected from AR antagonists (e.g., cyproterone acetate, spironolactone, bicalutamide, and enzalutamide), 5α-reductase inhibitors (e.g., finasteride and dutasteride), CYP17A1 inhibitors (e.g., abiraterone acetate), gonadotropin-releasing hormone (GnRH) analogs (e.g., leuprorelin and cetrorelix), and antigonadotropins (e.g., megestrol acetate and medroxyprogesterone acetate).

[0245] The methods herein contemplate administering an effective amount of a compound of Formula I and an effective amount of a second agent to achieve a desired or specified effect. The specific dosage and treatment regimen for any particular subject will depend on a variety of factors, including the activity of the specific compound used, age, body weight, general health, sex, diet, time of administration, rate of excretion, drug combination, severity and course of the disease, condition, or symptom, the subject's predisposition to the disease, condition, or symptom, and the judgment of the treating physician.

[0246] Once the subject's condition has improved, a maintenance dose of the compounds, compositions or combinations provided herein may be administered as needed. Thereafter, depending on the symptoms, the dosage or frequency of administration, or both, may be reduced to a level at which the improved condition is maintained when the symptoms have been alleviated to a desired level. However, the subject may require intermittent treatment over a long period of time if disease symptoms recur.

[0247] Activity evaluation Standard physiological, pharmacological, and biochemical procedures are available for testing compounds to identify those with the desired activity.

[0248] Such assays include, for example, cell-based assays, including the CTG proliferation assay described in the Examples section.

[0249] Enumerated Embodiments 1. A method of treating an androgen receptor mediated disorder in a patient having the disorder, comprising administering to the patient a therapeutically effective amount of a compound and a therapeutically effective amount of a second agent selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor, wherein the compound is represented by formula (I): [ka] (In the formula, R N is H, Each R 1 are independently halogen, CN and C 1~3 alkyl, R 2 and R 3 are each independently H and C 1~3 alkyl, or R 2 and R 3 and the carbon to which they are attached are substituted or unsubstituted C 3~6 forming a cycloalkyl, Each R 4 are independently substituted or unsubstituted C 1~3 alkyl or two R 4 The groups, together with the same carbon atom or adjacent carbon atoms to which they are attached, may form a substituted or unsubstituted C 3~6 Form a cycloalkyl or two R 4 groups, taken together with the non-adjacent carbon atoms to which they are attached, form a substituted or unsubstituted 4- to 7-membered heterocyclyl; X is N, L is -O(C 1~6alkyl)- or -(C 1~9 alkyl)-, n is 0 to 4, m is 0 to 8; V is [ka] where: A is N, CH or CR A and B is N, CH or CR B and Each R A are independently halogen, substituted or unsubstituted C 1~6 Alkyl and substituted or unsubstituted C 3~6 cycloalkyl; Each R B are independently halogen and substituted or unsubstituted C 1~6 alkyl, R C is a halogen or CF3, R 5 and R 6 is C 1~3 alkyl or R 5 and R 6 together with the carbon atoms to which they are attached, form a substituted or unsubstituted C 3~6 forming a cycloalkyl or a 3- to 6-membered heterocyclyl; a is 0 to 3, and b is 0 to 2) or a pharmaceutically acceptable salt, tautomer, isotopic substitution or stereoisomer thereof. 2.L is -O(CH2) p -or-(CH2) p and p is 1 to 3. 3.Each R 1 is independently selected from Cl, F, CN, and —CH 3 . 4. The method of embodiment 1, wherein n is 0. 5. The method of embodiment 1, wherein n is 1 or 2. 6.R2 and R 3 are each independently selected from H and methyl, or R 2 and R 3 and the carbon to which they are attached form an unsubstituted cyclopropyl. 7.Each R 4 are independently selected from methyl, CF3 and CH2OH, or two R 4 2. The method of embodiment 1, wherein the groups, together with the same carbon atom to which they are attached, form an unsubstituted cyclopropyl. 8. The method of embodiment 1, wherein m is 0, 1, 2, 3 or 4. 9. The Two R's 4 2. The method of embodiment 1, wherein the groups, taken together with the non-adjacent carbon atoms to which they are attached, form an unsubstituted 4- to 7-membered heterocyclyl. 10.Lは、-O(CH2)(CH2)-、-O(CH2)(CH(CH3))-、-O(CH2)(C(CH3)2)-、-O(CH(CH3))(CH2)-、-O(C(CH3)2)(CH2)-、-O(CH(CH3))(CH(CH3))-、-O(C H(CH3))(C(CH3)2)-、-O(C(CH3)2)(CH(CH3))-、-(CH2)-、-(CH2)(CH2)-、-(CH2)(CH2)(CH2)-、-(C(CH3)2)(C(CH3)2)-、-(CH(CH3))-、-(C(CH3) )2)-、-(CH(CH3))(CH(CH3))-、-(CH(CH3))(C(CH3)2)-、-(C(CH3)2)(CH(CH3))-、-(C(CH3)2)(C(CH3)2)-、-(CH3)(CH3)(CH(CH3))-、-(CH2)( CH(CH3))(CH2)-、-(CH(CH3))(CH2)(CH2)-、-(CH2)(CH2)(C(CH2)2)-、-(CH2)(C(CH2)2)(CH2)-、-(C(CH2)2)(CH2)(CH2)-、-(CH2)(CH(CH3))( CH(CH3))-、-(CH(CH3))(CH(CH3))(CH(CH3))-、-(CH(CH3))(CH(CH3))(CH2)-、-(CH(CH3))(CH2)(CH(CH3))-、-(CH2)(CH(CH3))(C(CH3)2)-、 -(CH(CH3))(CH2)(C(CH2)2)-、-(C(CH3)2)(CH2)(C(CH3)2)-、-(CH2)(C(CH3)2)(C(CH3)2)-、-(CH2)(C(CH3)2)(CH(CH3))-、-(CH(CH3)(C(CH3) )2)(CH2)-、-(C(CH3)2)(CH2)(CH(CH3))-、-(C(CH3)2)(CH(CH3))(CH2)-、-(C(CH3)2)(C(CH3)2)(CH2)-、-(CH(CH3))(CH(CH3))(C(CH3)2)-、- (CH(CH3))(C(CH3)2)(C(CH3)2)-、-(C(CH3)2)(CH(CH3))(C(CH3)2)-、-(CH(CH3))(C(CH3)2)(CH(CH3))-、-(C(CH3)2)(C(CH3)2)(CH(CH3))-、2. The method of embodiment 1, wherein the hydroxyl groups are -(C(CH)2)(CH(CH))(CH(CH))- and -(C(CH)2)(C(CH)2)(C(CH)2)-. 11. The method of embodiment 1, wherein L is -O(CH2)(CH2)-, -O(CH2)(CH(CH3))-, -O(CH(CH3))(CH2)-, or -(CH2)(CH2)(CH2)-. 12. The method of embodiment 1, wherein A is CH. 13. The method of embodiment 1, wherein B is CH. 14. The method of embodiment 1, wherein B is N. 15. The method of embodiment 1, wherein a is 0, 1 or 2. 16.Each R A are independently selected from Cl, Br, F, methyl, ethyl, n-propyl, isopropyl, isobutyl, sec-butyl, CF, CFCH, CHCHF, CHOH, CH(CH)OH, cyclopropyl, cyclobutyl, and cyclopentyl. 17. The method of embodiment 1, wherein b is 0 or 1. 18.R B 2. The method of embodiment 1, wherein R is methyl. 19.R C 2. The method of embodiment 1, wherein is CF or Cl. 20.R 5 and R 6 is methyl or R 5 and R 6 10. The method of embodiment 1, wherein: together with the carbon atom to which they are attached, form cyclobutyl, cyclopentyl, cyclohexyl, or tetrahydrofuranyl. 21. The compound is 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(2-chloro-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(2-chloro-4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(2-chloro-4-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(2-bromo-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-5-methylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(2-chloro-4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-methylphenyl)acetamide, 2-(4-(2-(2-chloro-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isobutylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-(4-(2-(2-chloro-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(2-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, (2S)-2-(4-(2-(2-chloro-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)acetamide, (2R)-2-(4-(2-(2-chloro-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-5-methylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, (S)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, (R)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(2-sec-butyl-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclobutylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-propylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(2-chloro-3-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclobutylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(2-sec-butyl-4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-propylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopentylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)acetamide, N-(2-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(2-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-(hydroxymethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-(hydroxymethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-(hydroxymethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-(hydroxymethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-2,4-dioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-4-oxo-2-thioxo-7-oxa-1,3-diazaspiro[4.4]nonan-1-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-4-oxo-2-thioxo-7-oxa-1,3-diazaspiro[4.4]nonan-1-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, (2S)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, (2R)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-ethylpyridin-2-yloxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2,3-difluorophenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,2-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,2-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,2-dimethylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,2-dimethylpiperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2,3-difluorophenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,2-dimethylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2,3-difluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)piperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-(4-(3-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenyl)propyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(3-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenyl)propyl)piperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(hydroxymethyl)phenoxy)ethyl)piperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1-hydroxyethyl)phenoxy)ethyl)piperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)piperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,2-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-2-methyl-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,2-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(7-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-4,7-diazaspiro[2.5]octan-4-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(7-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-4,7-diazaspiro[2.5]octan-4-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2,3-difluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(7-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-4,7-diazaspiro[2.5]octan-4-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(7-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-4,7-diazaspiro[2.5]octan-4-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((R)-4-(2-(4-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(7-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-4,7-diazaspiro[2.5]octan-4-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-(7-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-4,7-diazaspiro[2.5]octan-4-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-((S)-2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-((R)-2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, (2R)—N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)propanamide, (2S)—N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)propanamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((1S,4S)-5-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)acetamide, (2S)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)propanamide, (2R)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)propanamide, (2S)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, (2R)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((1R,4R)-5-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)acetamide, 2-((2R,5S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,5R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,5S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,5R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, 2-((2S,5S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,5S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, 2-((2R,5R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,5R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, 2-((2R,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((S)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-(4-(2-(4-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-2-methylpropanamide, 2-(4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2,2-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)piperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-((S)-2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-((R)-2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 1-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)cyclopropanecarboxamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-(2-fluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-(2-fluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-((2S,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-1-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)cyclopropanecarboxamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(5-chloro-6-cyanopyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,5R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(3-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((1S,4S)-5-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(3-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,5R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(3-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(3-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((1S,4S)-5-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((1R,4R)-5-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((1R,4R)-5-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((1R,4R)-5-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,5R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-ethylpyridin-2-yloxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 1-(4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)cyclopropanecarboxamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,5R)-4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-ethylpyridin-2-yloxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, (2R)—N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)propanamide, 2-((2R,5R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 1-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)cyclopropanecarboxamide, 2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, (2R)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-(trifluoromethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-(trifluoromethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,5R)-4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-isopropylpyridin-2-yloxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetamide, 2-((2R,6S)-4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-ethylpyridin-2-yloxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, 2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-isopropylpyridin-2-yloxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((2S,6R)-4-(2-(5-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-3-isopropylpyridin-2-yloxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-cyclopropylpyridin-2-yloxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(5-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-3-cyclopropylpyridin-2-yloxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-isopropylpyridin-2-yloxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(5-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-3-isopropylpyridin-2-yloxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-isopropylpyridin-2-yloxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2-(trifluoromethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-((S)-1-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)propan-2-yl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-((R)-1-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)propan-2-yl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(3-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-((R)-2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)propyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-((S)-2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)propyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-((R)-2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)propyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-((S)-2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)propyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,5R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, 2-((2R,5R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2-(trifluoromethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-(trifluoromethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethyl-5-fluorophenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethyl-6-fluorophenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethyl-6-methylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropyl-5-methylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethyl-5-methylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2-(trifluoromethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2-(trifluoromethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,6R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclobutylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-ethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2-ethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-cyclopropylphenoxy)ethyl)-2-ethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2-ethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-4-oxo-2-thioxo-1,3-diazaspiro[4.5]decan-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-4-oxo-2-thioxo-1,3-diazaspiro[4.4]nonan-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-4-oxo-2-thioxo-1,3-diazaspiro[4.4]nonan-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclobutylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethyl-3-methylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethyl-3-fluorophenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(3-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenyl)propyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, (2R)-2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, (2S)-2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, 2-((R)-4-(2-(2-chloro-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(3-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenyl)propyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, (2R)-2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, (2S)-2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, 2-((2S,6R)-4-(2-(2-chloro-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((2R,6S)-4-(3-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenyl)propyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-((S)-2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-((R)-2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(3-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenyl)propyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-((R)-2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-((S)-2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(2-chloro-4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-((2,6-dioxopiperidin-3-yl)amino)phenyl)acetamide, and 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-((2,6-dioxopiperidin-3-yl)amino)phenyl)acetamide, or a pharmaceutically acceptable salt thereof 21. The method of any one of embodiments 1 to 20, selected from the group consisting of: 22. The method of any one of embodiments 1-21, wherein the compound is (S)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide or a pharmaceutically acceptable salt thereof. 23. The method of any one of embodiments 1-21, wherein the compound is (S)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide. 24. The method of any one of embodiments 1-21, wherein the compound is 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide or a pharmaceutically acceptable salt thereof. 25. The method of any one of embodiments 1-21, wherein the compound is 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide. 26. The method of any one of embodiments 1-21, wherein the compound is 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide or a pharmaceutically acceptable salt thereof. 27. The method of any one of embodiments 1-21, wherein the compound is 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide. 28. The method of any one of embodiments 1-21, wherein the compound is 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide or a pharmaceutically acceptable salt thereof. 29. The method of any one of embodiments 1-21, wherein the compound is 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide. 30. The method of any one of embodiments 1-21, wherein the compound is N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide or a pharmaceutically acceptable salt thereof. 31. The method of any one of embodiments 1-21, wherein the compound is N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide. 32. The method of any one of embodiments 1-31, wherein the androgen-mediated disease is prostate cancer. 33. The method of embodiment 32, wherein the prostate cancer is castration-resistant prostate cancer (CRPC). 34. The method of any one of embodiments 1-33, wherein the second agent is selected from capivasertib, ipatasertib, AZD8186, 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, tazemetostat, ruxolitinib, and sorafenib. 35. The method of any one of embodiments 1-33, wherein the AKT inhibitor is selected from capivasertib and ipatasertib. 36. The method according to any one of embodiments 1 to 33, wherein the PI3K inhibitor is selected from a PI3K alpha inhibitor, a PI3K beta inhibitor and a PI3K delta inhibitor. 37. The method of any one of embodiments 1-33, wherein the PI3K inhibitor is AZD8186. 38. The method of any one of embodiments 1-33, wherein the BET inhibitor is 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid. 39. The method of any one of embodiments 1-33, wherein the EZH2 inhibitor is tazemetostat. 40. The method of any one of embodiments 1-33, wherein the JAK inhibitor is ruxolitinib. 41. The method of any one of embodiments 1-33, wherein the RAF kinase inhibitor is sorafenib. 42. The method of any one of embodiments 1-41, wherein the therapeutically effective amount of the compound is from about 0.01 mg / day to about 750 mg / day, from about 0.1 mg / day to about 375 mg / day, from about 0.1 mg / day to about 150 mg / day, from about 0.1 mg / day to about 75 mg / day, from about 0.1 mg / day to about 50 mg / day, from about 0.1 mg / day to about 25 mg / day, or from about 0.1 mg / day to about 10 mg / day. 43. The method of any one of embodiments 1-41, wherein the compound is administered once, twice, three times, four or more times per day. 44. The method of any one of embodiments 1-41, wherein the compound is administered at a dose of about 100 mg administered in a single daily dose. 45. The method of any one of embodiments 1-41, wherein the compound is administered at a dose of about 100 mg administered in two doses per day. 46. ​​The method of embodiment 39, wherein tazemetostat is administered in an amount of about 800 mg, 600 mg, 400 mg, or 200 mg. 47. The method of embodiment 39, wherein tazemetostat is administered in an amount of about 800 mg, 600 mg, 400 mg, or 200 mg twice a day. 48. The method of embodiment 40, wherein ruxolitinib is administered in an amount of about 5 mg, 10 mg, 15 mg, 20 mg, 25 mg. 49. The method of embodiment 40, wherein ruxolitinib is administered in an amount of about 5 mg, 10 mg, 15 mg, 20 mg, 25 mg twice daily. 50. The method of embodiment 41, wherein sorafenib is administered in an amount of about 300 mg or 400 mg. 51. The method of embodiment 41, wherein sorafenib is administered in an amount of about 300 mg or 400 mg twice a day. [Example]

[0250] Example 1: CTG proliferation assay This study was conducted to identify 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide and a second agent that could synergistically inhibit the growth of prostate cancer cell lines in an in vitro combination screen. Three prostate cancer cell lines, LNCaP, VCAP, and 22RV1, were used in this screen. Briefly, LNCaP cells were cultured in RPMI medium supplemented with 10% FBS, 1% penicillin / streptomycin, 10 mM HEPES, 1 mM sodium pyruvate, and 1.5 g / L sodium bicarbonate. LNCaP cells were seeded at a density of 2000 cells / well onto 384-black assay plates printed with combinations of our compounds of interest. PC3 cells were cultured in F12K medium supplemented with 10% FBS and 1% penicillin / streptomycin. 22RV1 cells were cultured in RPMI 1640 medium supplemented with 10% FBS and 1% penicillin / streptomycin. 22RV1 cells were seeded at a density of 2000 cells / well onto 384-black assay plates printed with combinations of our compounds of interest. VCaP cells were cultured on high-binding tissue culture flasks (Corning CellBIND) in DMEM medium supplemented with 10% FBS, 1% penicillin / streptomycin, 1 mM sodium pyruvate, and 1.5 g / L sodium bicarbonate to increase cell surface adhesion. VCaP cells were seeded at a density of 3000 cells / well onto high-binding 384-cell black assay plates printed with combinations of our compounds of interest. The seeded combination plates were then incubated at 37°C and 5% CO for 7 days. Cell viability assays were then performed on the plates using the Promega CellTiter-Glo (CTG) Luminescent Cell Viability Assay Kit according to the manufacturer's protocol.20 μL of CTG reagent was added to each well of a 384-well plate, and the plate was then incubated for 45 minutes before measuring fluorescence using a PerkinElmer EnVision Plate Reader.

[0251] statistical analysis Synergy is calculated by the Bliss and HSA excess scores. The BLISS and HSA excess scores are calculated by subtracting the area under the experimental response surface from the area under the corresponding reference model surface. A negative HSA excess score indicates antagonism, a positive HSA excess indicates additivity, and synergy is detected when the Bliss excess score is also positive. Replicates are integrated by fitting individual dose-response curves. Statistical analysis is performed by first estimating experimental noise and goodness-of-fit values ​​for each individual combination. These values ​​are used to calculate a Z-score for the observed effect. The Z-score is integrated across the combination matrix where deviations from the model are consistent across adjacent doses, and a p-value is calculated.

[0252] result Combinations with significant synergy scores (p<0.05) across all three cell lines tested are shown in Table 2. For the AKT inhibitor, synergy scores of 8 and 2 were obtained in the LNCAP and VCAP cell lines, respectively. For the panAKT inhibitor, synergy scores of 5.6, 2.1, and 1.5 were obtained in the LNCAP, 22RV1, and VCAP cell lines, respectively. For the PI3Kβ and PI3Kδ inhibitors, synergy scores of 1.6, 1.5, and 0.39 were obtained in the 22RV1, LNCAP, and VCAP cell lines, respectively. For the BET inhibitor, synergy scores of 2.8 and 1.3 were obtained in the VCAP and LNCAP cell lines, respectively. For the EZH2i, synergy scores of 4.1 were obtained in the LNCAP. For the JAK1 / 2i, synergy scores of 2 were obtained in the VCAP. For sorafenib, synergy scores of 0.65 were obtained in the 22RV1.

[0253] conclusion PIK3K / AKT, BET, JAK1 / 2, and EZH2 inhibitors showed significant synergy with Compound 1 in inhibiting the growth of prostate cancer cell lines.

[0254] [Table 100]

[0255] The embodiments provided herein may be more fully understood by reference to the following examples, which are intended to illustrate, but in no way limit, the pharmaceutical compositions and dosage forms provided herein.

[0256] The foregoing embodiments are intended to be illustrative only; those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific compounds, materials, and procedures. All such equivalents are considered to be within the scope of this invention and are covered by the appended claims.

Claims

1. 1. A method of treating an androgen receptor mediated disorder in a patient having the disorder, comprising administering to the patient a therapeutically effective amount of a compound and a therapeutically effective amount of a second agent selected from a PI3K inhibitor, an AKT inhibitor, a BET inhibitor, a JAK inhibitor, and an EZH2 inhibitor, wherein the compound is represented by formula (I): 【Chemistry 1】 (In the formula, R Ｎ is H, Each R １ are independently halogen, CN and C １～３ alkyl, R ２ and R ３ are each independently H and C １～３ alkyl, or R ２ and R ３ and the carbon to which they are attached may be substituted or unsubstituted C ３～６ forming a cycloalkyl, Each R ４ are independently substituted or unsubstituted C １～３ alkyl or two R ４ Groups, together with the same carbon atom or adjacent carbon atoms to which they are attached, may be substituted or unsubstituted C ３～６ Form a cycloalkyl, or two R ４ groups, taken together with the non-adjacent carbon atoms to which they are attached, form a substituted or unsubstituted 4- to 7-membered heterocyclyl; X is N; L is -O(C １～６ alkyl)- or -(C １～９ alkyl)-, n is 0 to 4; m is 0 to 8; V is, 【Chemistry 2】 where: A is N, CH or CR Ａ and B is N, CH or CR Ｂ and Each R Ａ are independently halogen, substituted or unsubstituted C １～６ Alkyl and substituted or unsubstituted C ３～６ cycloalkyl; Each R Ｂ are independently selected from halogen and substituted or unsubstituted C １～６ alkyl, R Ｃ is a halogen or CF ３ and R ５ and R ６ is C １～３ alkyl or R ５ and R ６ together with the carbon atom to which they are attached, form a substituted or unsubstituted C ３～６ forming a cycloalkyl or a 3- to 6-membered heterocyclyl, a is 0 to 3, and b is 0 to 2. or a pharmaceutically acceptable salt, tautomer, isotopic substitution or stereoisomer thereof.

2. Two R's ４ The method of claim 1, wherein the groups, taken together with the non-adjacent carbon atoms to which they are attached, form an unsubstituted 4- to 7-membered heterocyclyl.

3. L is -O(CH ２ ) (CH ２ ) -, -O(CH ２ ) (CH (CH ３ ))-,-O(CH(CH ３ )) (CH ２ ) - or -(CH ２ ) (CH ２ ) (CH ２ 2. The method of claim 1, wherein

4. Each R Ａ are independently Cl, Br, F, methyl, ethyl, n-propyl, isopropyl, isobutyl, sec-butyl, CF ３ , C.F. ２ CH ３ , C.H. ２ CH ２ F, CH ２ CHF ２ , C.H. ２ OH, CH(CH ３ 2. The method of claim 1, wherein the alkyl group is selected from the group consisting of cyclopropyl, cyclopropyl, cyclobutyl, and cyclopentyl.

5. The compound is 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(2-chloro-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(2-chloro-4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(2-chloro-4-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(2-bromo-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-5-methylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(2-chloro-4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-methylphenyl)acetamide, 2-(4-(2-(2-chloro-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isobutylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-(4-(2-(2-chloro-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(2-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, (2S)-2-(4-(2-(2-chloro-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)acetamide, (2R)-2-(4-(2-(2-chloro-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-5-methylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, (S)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, (R)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(2-sec-butyl-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclobutylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-propylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(2-chloro-3-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclobutylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(2-sec-butyl-4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-propylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopentylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)acetamide, N-(2-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(2-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-(hydroxymethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3-(hydroxymethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-(hydroxymethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-(hydroxymethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-2,4-dioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-4-oxo-2-thioxo-7-oxa-1,3-diazaspiro[4.4]nonan-1-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-4-oxo-2-thioxo-7-oxa-1,3-diazaspiro[4.4]nonan-1-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, (2S)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, (2R)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-ethylpyridin-2-yloxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2,3-difluorophenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,2-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,2-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,2-dimethylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,2-dimethylpiperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2,3-difluorophenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,2-dimethylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2,3-difluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)piperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-(4-(3-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenyl)propyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(3-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenyl)propyl)piperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(hydroxymethyl)phenoxy)ethyl)piperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1-hydroxyethyl)phenoxy)ethyl)piperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)piperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,2-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(4-cyano-2-methyl-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,2-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(7-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-4,7-diazaspiro[2.5]octan-4-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(7-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-4,7-diazaspiro[2.5]octan-4-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2,3-difluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(7-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-4,7-diazaspiro[2.5]octan-4-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(7-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-4,7-diazaspiro[2.5]octan-4-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((R)-4-(2-(4-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(7-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-4,7-diazaspiro[2.5]octan-4-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-(7-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-4,7-diazaspiro[2.5]octan-4-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-((S)-2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-((R)-2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, (2R)—N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)propanamide, (2S)—N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)propanamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((1S,4S)-5-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)acetamide, (2S)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)propanamide, (2R)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)propanamide, (2S)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, (2R)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((1R,4R)-5-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)acetamide, 2-((2R,5S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,5R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,5S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,5R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, 2-((2S,5S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,5S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, 2-((2R,5R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,5R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, 2-((2R,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((S)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-(4-(2-(4-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-2-methylpropanamide, 2-(4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2,2-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)piperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-((S)-2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-((R)-2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 1-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)cyclopropanecarboxamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-(2-fluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-(2-fluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-((2S,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-1-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)cyclopropanecarboxamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2-fluoroethyl)phenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(5-chloro-6-cyanopyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,5R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(3-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((1S,4S)-5-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(3-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)acetamide, 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(2,2-difluoroethyl)phenoxy)ethyl)piperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,5R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(3-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(3-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((1S,4S)-5-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((1R,4R)-5-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((1R,4R)-5-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((1R,4R)-5-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,5-diazabicyclo[2.2.2]octan-2-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,5R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-ethylpyridin-2-yloxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 1-(4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)cyclopropanecarboxamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,5R)-4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-ethylpyridin-2-yloxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, (2R)—N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)propanamide, 2-((2R,5R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 1-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)cyclopropanecarboxamide, 2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, (2R)-2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, 2-((R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-(trifluoromethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-(trifluoromethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,5R)-4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-isopropylpyridin-2-yloxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetamide, 2-((2R,6S)-4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-ethylpyridin-2-yloxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, 2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(5-(2,6-dioxopiperidin-3-ylamino)-2-fluorophenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-chloro-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-isopropylpyridin-2-yloxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((2S,6R)-4-(2-(5-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-3-isopropylpyridin-2-yloxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-cyclopropylpyridin-2-yloxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(5-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-3-cyclopropylpyridin-2-yloxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-isopropylpyridin-2-yloxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(5-(7-(4-cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-3-isopropylpyridin-2-yloxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(5-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-3-isopropylpyridin-2-yloxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2-(trifluoromethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-((S)-1-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)propan-2-yl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-((R)-1-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)propan-2-yl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-(3-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-3,8-diazabicyclo[3.2.1]octan-8-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-((R)-2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)propyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-((S)-2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)propyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-((R)-2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)propyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-((S)-2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)propyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2R,5R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)acetamide, 2-((2R,5R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2-(trifluoromethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-(trifluoromethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethyl-5-fluorophenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethyl-6-fluorophenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethyl-6-methylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropyl-5-methylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethyl-5-methylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2-(trifluoromethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-isopropylphenoxy)ethyl)-2-(trifluoromethyl)piperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, N-(3-cyano-5-(2,6-dioxopiperidin-3-ylamino)phenyl)-2-((2S,6R)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclobutylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-ethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2-ethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-cyclopropylphenoxy)ethyl)-2-ethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2-ethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-4-oxo-2-thioxo-1,3-diazaspiro[4.5]decan-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-4-oxo-2-thioxo-1,3-diazaspiro[4.4]nonan-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-4-oxo-2-thioxo-1,3-diazaspiro[4.4]nonan-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclobutylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-(1,1-difluoroethyl)phenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethyl-3-methylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethyl-3-fluorophenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,5R)-4-(3-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenyl)propyl)-2,5-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, (2R)-2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, (2S)-2-((S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, 2-((R)-4-(2-(2-chloro-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((S)-4-(3-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenyl)propyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, (2R)-2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, (2S)-2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)propanamide, 2-((2S,6R)-4-(2-(2-chloro-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)-5-fluorophenyl)acetamide, 2-((2R,6S)-4-(3-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenyl)propyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-((S)-2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-((R)-2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(3-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluorophenyl)propyl)-2,6-dimethylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-((R)-2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2R,6S)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-cyclopropylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-((S)-2,6-dioxopiperidin-3-ylamino)phenyl)acetamide, 2-((2S,6R)-4-(2-(2-chloro-4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-((2,6-dioxopiperidin-3-yl)amino)phenyl)acetamide, and 2-((2S,6R)-4-(2-(4-(3-(3-chloro-4-cyanophenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2,6-dimethylpiperazin-1-yl)-N-(3-((2,6-dioxopiperidin-3-yl)amino)phenyl)acetamide, or a pharmaceutically acceptable salt thereof The method of any one of claims 1 to 4, wherein the compound is selected from the group consisting of:

6. 6. The method of any one of claims 1 to 5, wherein the compound is 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide or a pharmaceutically acceptable salt thereof.

7. 6. The method of any one of claims 1 to 5, wherein the compound is 2-((R)-4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)-2-methylpiperazin-1-yl)-N-(3-(2,6-dioxopiperidin-3-ylamino)phenyl)acetamide.

8. The method of any one of claims 1 to 7, wherein the androgen-mediated disease is prostate cancer.

9. 9. The method of claim 8, wherein the prostate cancer is castration-resistant prostate cancer (CRPC).

10. 10. The method of any one of claims 1 to 9, wherein the second agent is selected from capivasertib, ipatasertib, AZD8186, 6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, tazemetostat, ruxolitinib, and sorafenib.

11. 11. The method of any one of claims 1-10, wherein the therapeutically effective amount of the compound is from about 0.01 mg / day to about 750 mg / day, from about 0.1 mg / day to about 375 mg / day, from about 0.1 mg / day to about 150 mg / day, from about 0.1 mg / day to about 75 mg / day, from about 0.1 mg / day to about 50 mg / day, from about 0.1 mg / day to about 25 mg / day, or from about 0.1 mg / day to about 10 mg / day.

12. 12. The method of any one of claims 1 to 11, wherein the compound is administered once, twice, three times, four or more times daily.

13. 13. The method of any one of claims 1 to 12, wherein the compound is administered in a dose of about 100 mg administered in a single daily dose.

14. 13. The method of any one of claims 1 to 12, wherein the compound is administered at a dose of about 100 mg administered in two doses per day.

15. 11. The method of claim 10, wherein the second agent is tazemetostat administered in an amount of about 800 mg, 600 mg, 400 mg, or 200 mg.

16. 16. The method of claim 15, wherein tazemetostat is administered in an amount of about 800 mg, 600 mg, 400 mg, or 200 mg twice daily.

17. 11. The method of claim 10, wherein the second agent is ruxolitinib administered in an amount of about 5 mg, 10 mg, 15 mg, 20 mg, 25 mg.

18. 18. The method of claim 17, wherein ruxolitinib is administered in an amount of about 5 mg, 10 mg, 15 mg, 20 mg, 25 mg twice daily.

19. 11. The method of claim 10, wherein the second agent is sorafenib administered in an amount of about 300 mg or 400 mg.

20. 20. The method of claim 19, wherein sorafenib is administered in an amount of about 300 mg or 400 mg twice daily.

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