Cdk protein degraders, pharmaceutical compositions, and therapeutic applications

Abstract

Provided herein are CDK protein degraders, e.g., a compound of Formula (I), and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a CDK-mediated disorder, disease, or condition.

Description

CDK PROTEIN DEGRADERS, PHARMACEUTICAL COMPOSITIONS, ANDTHERAPEUTIC APPLICATIONSCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of the priority of U.S. Provisional Application Nos. 63 / 364,470, filed May 10, 2022; 63 / 378,671, filed October 6, 2022; and 63 / 496,380, filed April 14, 2023; the disclosure of each of which is incorporated herein by reference in its entirety.FIELD

[0002] Provided herein are CDK protein degraders and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a CDK-medlated disorder, disease, or condition.BACKGROUND

[0003] Cyclin-dependent kinases (CDKs) are protein kinases that are involved in critical cellular processes, such as a cell cycle. Malumbres etal., Nat. Cell Biol. 2009, 11, 1275-6; Ding et al., Int. J. Mol. Sci. 2020, 21, 1960. CDKs associate with different cyclins to control different cell cycle transitions in human cells Uzbekov and Prigent, Cells 2020, 11, 704. There are 20 CDKs and about 30 cyclins in the human. Malumbres et al., Nat. Cell Biol. 2009, 11, 1275-6. CDK2 complexed with cyclin E, or CDK4 / CDK6 complexed with cyclin D drives cell-cycle progression from G1 to S phase. Topacio et al., Mol. Cell 2019, 74, 758-70, Uzbekov and Prigent, Cells 2020, 11, 704. Cell cycle dysregulation characterized by aberrant activation of CDKs is a hallmark of cancer. Malumbres and Barbacid, Nat. Rev. Cancer 2009, 9, 153-66; Otto and Sicinski, Nat. Rev. Cancer 2017, 17, 93-115; Ding et al., Int. J. Mol. Sci. 2020, 21, 1960.Dual CDK4 / 6 inhibitors, palbociclib, ribociclib, and abemaciclib, have been approved by the FDA for treating advanced or metastatic hormone receptor positive breast cancer. Sanchez- Martinez et al., Bioorg. Med. Chem. Lett. 2019, 29, 126637; Zhang el al., Am. J. Cancer Res. 2021, 11, 1913-35. The efficacy of CDK4 / CDK6 inhibition is, however, limited by innate or acquired resistance. Alvarez-Fernandez and Malumbres, Cancer Cell 2020, 37, 514-29; Ogata et al., Breast Cancer 2021, 28, 206-15.

[0004] Despite the advances in cancer treatment, cancer remains a major worldwide public health problem. It was estimated that there will be 1,918,030 new cancer cases diagnosed and 609,360 cancer deaths in the US alone in 2022. Cancer Facts de Figures 2022. Therefore, there is a need for an effective therapy for cancer treatment.SUMMARY OF THE DISCLOSURE

[0005] Provided herein is a compound of Formula (I):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein:A is a bond, heterocyclylene, or -S(O2)-;E is C6-14 arylene, heteroarylene, or heterocyclylene;L is a linker;X is a bond or --C(O)--;R1is (i) hydrogen; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) ~C(O)Rla, -C(O)ORla, -C(O)NRlbRlc, -C(O)SRla, -C(NRia)NRlbRlc, -C(S)Rla, -C(S)ORla, -C(S)NRlbRlc, -S(O)Rla, -S(O)2Rla, -S(O)NRlbRlc, or -S(O)2NRlbRlc;R2, R3, and R4are each independently (i) hydrogen, deuterium, cyano, halo, or nitro; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) -C(O)Rla, -C(O)ORla, -C(O)NRlbRlc, -C(O)SRla, -C(NRla)NRlbRlc, -C(S)Rla, ~C(S)ORla, -C(S)NRibRlc, -ORla, -OC(O)Rla, -OC(O)ORla, -OC(O)NRlbRlc, -OC(O)SRla, -OC(NRla)NRlbRlc, -OC(S)Rla, -OC(S)ORla, -OC(S)NRlbRlc, -OS(O)Rla, -OS(O)2Ria, -OS(O)NRlbRk, -OS(O)2NRlbRk, -NRlbRk, -NRlaC(O)Rld, ~NRlaC(O)ORld, -NRlaC(O)NRlbRle, -NRlaC(O)SRld, -NRlaC(NRld)NRlbRlc, -NRlaC(S)Rld, -NRlaC(S)ORld, -NRlaC(S)NRlbRlc, -NRlaS(O)Rld, -NR!aS(O)2Rld, -NRlaS(O)NRlbRlc, -NRlaS(O)2NRlbRk-SRla, -S(O)Rla, -S(O)2Rla, -S(O)NRlbRk, or -S(O)2NRlbRk;wherein: each AEis independently a bond, -O-, -N(Rlb)---, --S-, C1-6 alkylene, Ci-6 heteroalkylene, C2-6 alkenylene, C2-6 heteroalkenyl ene, CM alkynylene, C2-6 heteroalkynylene, C3-10 cycloalkylene, Ce-i4 arylene, C7-15 aralkylene, heteroarylene, heterocyclylene, CM heteroalkylene-C6-i4 arylene, vC1-6 heteroalkylene-heterocyclylene, or C2-6 alkynylene-heterocyclylene; each XEis independently C(RE1) or N;YEis a bond, CM alkylene, -O-, -S-, -S(O)-, ~S(O2)-, or -N(RE3)-;Z is -CH2- or --C(O)-; one of Z1, Z2, Z3, and Z4is -C= and the remaining three of Z1, Z2, Z3, and Z4are each independently -C(RE4a)=; or Z!is a bond; one of Z2, Z3, and Z4is C=, and the remaining two of Z2, Z3, and Z4are each independently -C(RE4a)= or -S-; each RE1is independently hydrogen, deuterium, halo, or C1-6 alkyl; each RE2, RE3, and RE3is independently hydrogen or C1-6 alkyl; each RE4is independently (i) deuterium, cyano, halo, or nitro; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) -C(O)Rla, -C(O)ORla, -C(O)NRlbRlc, -C(O)SRla, -C(NRla)NRlbRlc, -C(S)Rla, -C(S)ORla, -C(S)NRlbRlc, -ORla, -OC(O)Rla, -OC(O)ORla, -OC(O)NRlbRlc, -OC(O)SRla, -OC(NRla)NRlbRlc, -OC(S)Rla,OC(S)ORla, -OC(S)NRlbRlc, -OS(O)Rla, -OS(O)2Rla, -OS(O)NRlbRlc, -OS(O)2NRlbRic, -NRibRlc, -NRlaC(O)Rld, -NRlaC(O)ORld, -NRlaC(O)NRlbRlc, -NRlaC(O)SRld, -NRlaC(NRld)NRlbRlc, -NRlaC(S)Rld, -NRlaC(S)ORld,■~NRlaC(S)NRlbRlc, -NRlaS(O)Rld, -NRlaS(O)2Rld, -NRlaS(O)NRlbRlc,-NRlaS(O)2NRlbRlc, -SRla, -S(O)Rla, -S(O)2Rla, -S(O)NRlbRlc, or -S(O)2NRlbRlc; each RE4ais independently hydrogen or RE4; each m is independently an integer of 0, 1, or 2; and each n is independently an integer of 0, 1, 2, or 3; and each Ria, Rlb, Rlc, and Rldis independently hydrogen, deuterium, C1-6 alkyl, Ci-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; wherein each alkyl, alkylene, heteroalkyl, heteroalkylene, alkenyl, alkenylene, heteroalkenylene, alkynyl, alkynylene, heteroal kynylene, cycloalkyl, cycloalkylene, aryl, arylene, aralkyl, aralkylene, heteroaryl, heteroarylene, heterocyclyl, and heterocyclylene is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, wherein each Q is independently selected from: (a) deuterium, cyano, halo, imino, nitro, and oxo; (b) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; and (c) -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -C(O)SRa, -C(NRa)NRbRc, -C(S)Ra, -C(S)ORa, -C(S)NRbRc, ORa, -OC(O)Ra, -OC(O)ORa, -OC(O)NRbRc, -OC(O)SRa, -OC(NRa)NRbRc, -OC(S)Ra, -OC(S)ORa, -OC(S)NRbRc, OP(O)(ORb)ORc, OS(O)Ra, -OS(O)2Ra, -OS(O)NRbRc, OS(O)2NRbRc, -NRbRc, -NRaC(O)Rd, -NRaC(O)ORd, -NRaC(O)NRbRc, -NRaC(O)SRd, -NRaC(NRd)NRbRc, -NRaC(S)Rd, -NRaC(S)ORd, -NRaC(S)NRbRc, -NRaS(O)Rd, -NRaS(O)2Rd, -NRaS(O)NRbRc, -NRaS(O)2NRbRc, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRbRc, and ~S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rdis independently (i) hydrogen or deuterium; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; or (iii) Rband Rctogether with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; wherein each Qais independently selected from: (a) deuterium, cyano, halo, nitro, imino, and oxo; (b) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Co-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl; and (c) -C(O)Re, -C(O)ORe, -C(O)NRfRg, -C(O)SRe,-C(NRe)NRfRg, -C(S)Re, -C(S)ORe, -C(S)NRfRg, -0Re, -OC(O)Re, -OC(O)ORe, -OC(O)NRfRs, -OC(O)SRe, -OC(NRe)NRfRs, -OC(S)Re, -OC(S)ORe, -OC(S)NRfR8, -OP(O)(ORf)ORg, -OS(O)Re, -OS(O)2Re, -OS(O)NRfRg, -OS(O)2NRfR8, -NRfRg, -NReC(O)Rh, -NReC(O)ORf, -NReC(O)NRfRg, -NReC(O)SRf, ~NReC(NRh)NRfRg, -NReC(S)Rh, -NReC(S)ORf, -NReC(S)NRiRg, -NReS(O)Rh, ~NReS(O)2Rh, ~NReS(O)NRfRg-NReS(O)2NRfRg, -SRe, -S(O)Re, -S(O)2Re, -S(O)NRfRg, and -S(O)2NRfRg; wherein each Re, Rf, Rg, and Rhis independently (i) hydrogen or deuterium; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) Rfand Rgtogether with the N atom to which they are attached form heterocyclyl.

[0006] Also provided herein is a pharmaceutical composition comprising a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; and a pharmaceutically acceptable excipient.

[0007] Additionally provided herein is a method of treating, preventing, or ameliorating one or more symptoms of a disorder, disease, or condition mediated by a CDK in a subject, comprising administering to the subject in need thereof a therapeutically effective amount of a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0008] Furthermore, provided herein is a method of treating, preventing, or ameliorating one or more symptoms of a proliferative disease in a subject, comprising administering to the subject in need thereof a therapeutically effective amount of a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0009] Provided herein is a method of inhibiting the growth of a cell, comprising contacting the cell with an effective amount of a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, amixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0010] Provided herein is a method of inducing degradation of a CDK, comprising contacting the CDK with an effective amount of a compound of Formula (I), or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.DETAILED DESCRIPTION

[0011] To facilitate understanding of the disclosure set forth herein, a number of terms are defined below.

[0012] Generally, the nomenclature used herein and the laboratory procedures in organic chemistry, medicinal chemistry, biochemistry, biology, and pharmacology described herein are those well-known and commonly employed in the art. Unless defined otherwise, 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.

[0013] The term “subject” refers to an animal, including, but not limited to, a primate (e.g., human), cow, pig, sheep, goat, horse, dog, cat, rabbit, rat, or mouse. The terms “subject” and “patient” are used interchangeably herein in reference, for example, to a mammalian subject, such as a human subject. In one embodiment, the subject is a human.

[0014] The terms “treat,” “treating,” and “treatment” are meant to include alleviating or abrogating a di sorder, disease, or condition, or one or more of the symptoms associated with the disorder, disease, or condition; or alleviating or eradicating the cause(s) of the disorder, disease, or condition itself.

[0015] The terms “prevent,” “preventing,” and “prevention” are meant to include a method of delaying and / or precluding the onset of a disorder, disease, or condition, and / or its attendant symptoms; barring a subject from acquiring a disorder, disease, or condition; or reducing a subject’s risk of acquiring a disorder, disease, or condition.

[0016] The terms “alleviate” and “alleviating” refer to easing or reducing one or more symptoms (e.g., pain) of a disorder, disease, or condition. The terms can also refer to reducing adverse effects associated with an active ingredient. Sometimes, the beneficial effects that a subject derives from a prophylactic or therapeutic agent do not result in a cure of the disorder, disease, or condition.

[0017] The term “contacting” or “contact” is meant to refer to bringing together of a therapeutic agent and a biological molecule (e.g., a protein, enzyme, RNA, or DNA), cell, or tissue such that a physiological and / or chemical effect takes place as a result of such contact. Contacting can take place in vitro, ex vivo, or in vivo. In one embodiment, a therapeutic agent is contacted with a biological molecule in vitro to determine the effect of the therapeutic agent on the biological molecule. In another embodiment, a therapeutic agent is contacted with a cell in cell culture (in vitro) to determine the effect of the therapeutic agent on the cell. In yet another embodiment, the contacting of a therapeutic agent with a biological molecule, cell, or tissue includes the administration of a therapeutic agent to a subject having the biological molecule, cell, or tissue to be contacted.

[0018] The term “therapeutically effective amount” or “effective amount” is meant to include the amount of a compound that, when administered, is sufficient to prevent development of, or alleviate to some extent, one or more of the symptoms of the disorder, disease, or condition being treated. The term “therapeutically effective amount” or “effective amount” also refers to the amount of a compound that is sufficient to elicit a biological or medical response of a biological molecule (e.g., a protein, enzyme, RNA, or DNA), cell, tissue, system, animal, or human, which is being sought by a researcher, veterinarian, medical doctor, or clinician.

[0019] The term “ICso” or “ECso” refers to an amount, concentration, or dosage of a compound that is required for 50% inhibition of a maximal response in an assay that measures such a response.

[0020] The term “pharmaceutically acceptable carrier,” “pharmaceutically acceptable excipient,” “physiologically acceptable carrier,” or “physiologically acceptable excipient” refers to a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, solvent, or encapsulating material. In one embodiment, each component is“pharmaceutically acceptable” in the sense of being compatible with the other ingredients of a pharmaceutical formulation, and suitable for use in contact with the tissue or organ of a subject (e.g., a human) without excessive toxicity, irritation, allergic response, immunogenicity, or other problems or complications, and commensurate with a reasonable benefit / risk ratio. See, e.g., Remington: The Science and Practice of Pharmacy, 23rd ed.; Adejare Ed.; Academic Press, 2020; Handbook of Pharmaceutical Excipients, 9th ed.; Sheskey et al., Eds.; Pharmaceutical Press, 2020; Handbook of Pharmaceutical Additives, 3rd ed.; Ash and Ash Eds.; Synapse Information Resources, 2007; Pharmaceutical Preformulation and Formulation, 2nd ed.; Gibson Ed., CRC Press, 2009.

[0021] The term “about” or “approximately” means an acceptable error for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined. In certain embodiments, the term “about” or “approximately” means within 1, 2, or 3 standard deviations. In certain embodiments, the term “about” or “approximately” means within 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, or 0.05% of a given value or range

[0022] The term “alkyl” refers to a linear or branched saturated monovalent hydrocarbon radical, wherein the alkyl is optionally substituted with one or more substituents Q as described herein. For example, C1-6 alkyl refers to a linear saturated monovalent hydrocarbon radical of 1 to 6 carbon atoms or a branched saturated monovalent hydrocarbon radical of 3 to 6 carbon atoms. In certain embodiments, the alkyl is a linear saturated monovalent hydrocarbon radical that has 1 to 20 (C1-20), 1 to 15 (C1-15), 1 to 10 (C1-10), or 1 to 6 (Ci-e) carbon atoms, or branched saturated monovalent hydrocarbon radical of 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10), or 3 to 6 (C3-6) carbon atoms. As used herein, linear C1-6 and branched C3-6 alkyl groups are also referred as “lower alkyl.” Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl (including all isomeric forms, e.g., w-propyl and isopropyl), butyl (including all isomeric forms, e.g., w-butyl, isobutyl, sec-butyl, and Ebutyl), pentyl (including all isomeric forms, e.g., n-pentyl, isopentyl, sec-pentyl, neopentyl, and tert-pentyl), and hexyl (including all isomeric forms, e.g., w-hexyl, isohexyl, and sec-hexyl).

[0023] The terms “alkylene” and “alkanediyl” are used interchangeably herein inreference to a linear or branched saturated divalent hydrocarbon radical, wherein the alkanediyl is optionally be substituted with one or more substituents Q as described herein. For example, C1-6 alkanediyl refers to a linear saturated divalent hydrocarbon radical of 1 to 6 carbon atoms or a branched saturated divalent hydrocarbon radical of 3 to 6 carbon atoms. In certain embodiments, the alkanediyl is a linear saturated divalent hydrocarbon radical that has 1 to 30 (C1-30), 1 to 20 (C1-2.0), 1 to 15 (Ci-15), 1 to 10 (C1-10), or 1 to 6 (Ci-e) carbon atoms, or branched saturated divalent hydrocarbon radical of 3 to 30 (C3-30), 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10), or 3 to 6carbon atoms. As used herein, linear C1-6 and branched C3-6 alkanediyl groups are also referred as “lower alkanediyl.” Examples of alkanediyl groups include, but are not limited to, methanediyl, ethanediyl (including all isomeric forms, e.g., ethane- 1,1 -diyl and ethane- 1,2-diyl), propanediyl (including all isomeric forms, e.g,, propane- 1,1 -diyl, propane-1, 2- diyl, and propane- 1,3 -diyl), butanediyl (including all isomeric forms, e.g., butane-l, l-diyl, butane- 1,2-diyl, butane- 1,3 -diyl, and butane-l,4-diyl), pentanediyl (including all isomeric forms, e.g., pentane-l,l-diyl, pentane-l,2-diyl, pentane- 1,3 -diyl, and pentane- 1,5 -diyl), and hexanediyl (including all isomeric forms, e.g., hexane-l,l-diyl, hexane- 1,2-diyl, hexane- 1,3 -diyl, and hexane- 1,6-diyl). Examples of substituted alkanediyl groups include, but are not limited to, -C(O)CH2-, -C(O)(CH2)2-, -C(O)(CH2)3-, -C(O)(CH2)4- -C(O)(CH2)5-, -C(O)(CH2)6-, -C(O)(CH2)7-, -C(O)(CH2>- -C(O)(CH2)9-, -C(0)(CH2)IO-, -C(O)CH2C(O)- -C(O)(CH2)2C(O)-, -C(O)(CH2)3C(O)-, -C(O)(CH2)4C(O)-, or -C(O)(CH2)5C(O)-.

[0024] The term “heteroalkyl” refers to a linear or branched saturated monovalent hydrocarbon radical that contains one or more heteroatoms on its main chain, each independently selected from O, S, and N. The heteroalkyl is optionally substituted with one or more substituents Q as described herein. For example, C1-6 heteroalkyl refers to a linear saturated monovalent hydrocarbon radical of 1 to 6 carbon atoms or a branched saturated monovalent hydrocarbon radical of 3 to 6 carbon atoms. In certain embodiments, the heteroalkyl is a linear saturated monovalent hydrocarbon radical that has 1 to 20 (C1-20), 1 to 15 (Ci-15), 1 to 10 (Ci-10), or 1 to 6 (C1-6) carbon atoms, or branched saturated monovalent hydrocarbon radical of 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C.3-10), or 3 to 6 (C3-6) carbon atoms. As used herein, linear C1-6 and branched C3-6 heteroalkyl groups are also referred as “lower heteroalkyl.” Examples of heteroalkyl groups include, but are not limited to, --OCH3, -OCH2.CH3, -CH2.OCH3, -NHCHs, -ONHCH3, -NHOCH3, -SCH3, -CH2NHCH2CH3, and -NHCH2CH2CH3. Examples ofsubstituted heteroalkyl groups include, but are not limited to, -CH2NHC(O)CH3and -NHC(O)CH2CH3.

[0025] The terms “heteroalkylene” and “heteroalkanediyl” are used interchangeably herein in reference to a linear or branched saturated divalent hydrocarbon radical that contains one or more heteroatoms in its main chain, each independently selected from 0, S, and N. The heteroalkylene is optionally substituted with one or more substituents Q as described herein. For example, C1-6 heteroalkylene refers to a linear saturated divalent hydrocarbon radical of 1 to 6 carbon atoms or a branched saturated divalent hydrocarbon radical of 3 to 6 carbon atoms. In certain embodiments, the heteroalkylene is a linear saturated divalent hydrocarbon radical that has 1 to 20 (Ci -20), 1 to 15 (C1-15), 1 to 10 (C1-10), or 1 to 6 (C1-6) carbon atoms, or branched saturated divalent hydrocarbon radical of 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10), or 3 to 6 (C3-6) carbon atoms. As used herein, linear C1-6 and branched C3-6 heteroalkylene groups are also referred as “lower heteroalkylene ” Examples of heteroalkyl ene groups include, but are not limited to,-(CH2)7O-, ~(CH2)8O--, -(CH2)9O-, ~(CH2)IOO-, -CH2OCH2-, -CIECIEO-, -(CH2CH2O)2-(CH2CH2O)3 --(CH2CH2O)4--, (CH2CH2O)5-CH2NH -CH2NHCH2-, CH2CH2NH- CH2CH2CH2NH- -(CH2)4NH- -CH2S- -CH2SCH2-, and -CH2CH2S- Examples of substituted heteroalkylene groups include, but are not limited to, C(O)CH2O C(O)(CH2)2O -, -C(O)CH2CH2CH2O- -C(O)CH2CH2CH2CH2O-, -C(O)(CH2)5O- -C(O)(CH2)6O- -C(O)(CH2)7O-, -C(O)(CH2)SO-, -C(O)(CH2)9O- -C(0)(CH2)IOO-, -C(O)CH2OCH2CH2O- -C(O)CH2O(CH2CH2O)2--, --C(O)CH2O(CH2CH2O)3-, ~C(O)CH2.O(CH2CH2O)4, -C(O)CH2O(CH2CH2O)5- -CH2NHC(O)CH2-, -CH2CH2C(O)NH-, -CH2N(CH3)-, -(CH2)2N(CH3)-, -(CH2)3N(CH3)-, or ~(CH2)4N(CH3)-.

[0026] The term “alkenyl” refers to a linear or branched monovalent hydrocarbon radical, which contains one or more, in one embodiment, one, two, three, or four, in another embodiment, one, carbon-carbon double bond(s). The alkenyl is optionally substituted with one or more substituents Q as described herein. The term “alkenyl” embraces radicals having a “czx” or “trans" configuration or a mixture thereof, or alternatively, a “Z” or “E” configuration or a mixture thereof, as appreciated by those of ordinary skill in the art. For example, C2.-6 alkenyl refers to a linear unsaturated monovalent hydrocarbon radical of 2 to 6 carbon atoms or abranched unsaturated monovalent hydrocarbon radical of 3 to 6 carbon atoms. In certain embodiments, the alkenyl is a linear monovalent hydrocarbon radical of 2 to 20 (C2-20), 2 to 15 (C2-15), 2 to 10 (C2-10), or 2 to 6 (C2-0) carbon atoms, or a branched monovalent hydrocarbon radical of 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10), or 3 to 6carbon atoms. Examples of alkenyl groups include, but are not limited to, ethenyl, propenyl (including all isomeri c forms, e.g., propen- 1-yl, propen-2-yl, and allyl), and butenyl (including all isomeric forms, e.g, buten- 1-yl, buten-2-yl, buten-3-yl, and 2-buten-l-yl).

[0027] The terms “alkenylene” and “alkenediyl” are used interchangeably herein in reference to a linear or branched divalent hydrocarbon radical, which contains one or more, in one embodiment, one, two, three, or four, in another embodiment, one, carbon-carbon double bond(s). The alkenediyl is optionally substituted with one or more substituents Q as described herein. The term “alkenediyl” embraces radicals having a “cis” or “ trans'" configuration or a mixture thereof, or alternatively, a “Z” or “E” configuration or a mixture thereof, as appreciated by those of ordinary skill in the art. For example, C2-6 alkenediyl refers to a linear unsaturated divalent hydrocarbon radical of 2 to 6 carbon atoms or a branched unsaturated divalent hydrocarbon radical of 3 to 6 carbon atoms. In certain embodiments, the alkenediyl is a linear divalent hydrocarbon radical of 2 to 30 (€2-30), 2 to 20 (C2-20), 2 to 15 (C2-15), 2 to 10 (€2-10), or 2 to 6 (C2-6) carbon atoms, or a branched divalent hydrocarbon radical of 3 to 30 (C3-30), 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10), or 3 to 6 (C3-6) carbon atoms. Examples of alkenediyl groups include, but are not limited to, ethenediyl (including all isomeric forms, e.g. , ethene- 1 ,1- diyl and ethene- 1,2-diyl), propenediyl (including all isomeric forms, e.g., 1 -propene- 1,1 -diyl, 1- propene- 1,2-diyl, and 1 -propene- 1,3 -diyl), butenediyl (including all isomeric forms, e.g, 1- butene- 1,1 -diyl, l-butene-l,2-diyl, and 1 -butene- 1,4-diyl), pentenediyl (including all isomeric forms, e.g., 1 -pentene- 1,1 -diyl, 1 -pentene- 1,2-diyl, and 1 -pentene- 1,5 -diyl), and hexenediyl (including all isomeric forms, e.g, 1 -hexene- 1,1 -diyl, l-hexene-l,2-diyl, l-hexene-l,3-diyl, 1- hexene- 1,4-diyl, l-hexene-l,5-diyl, and l-hexene-l,6-diyl).

[0028] The terms “heteroalkenylene” and “heteroalkenediyl” are used interchangeably herein in reference to a linear or branched divalent hydrocarbon radical, which contains one or more, in one embodiment, one, two, three, or four, in another embodiment, one, carbon-carbon double bond(s), and which contains one or more heteroatoms each independently selected from0, S, and N in the hydrocarbon chain. The heteroalkenylene is optionally substituted with one or more substituents Q as described herein. The term “heteroalkenylene” embraces radicals having a “cz's” or “trans” configuration or a mixture thereof, or alternatively, a “Z” orconfiguration or a mixture thereof, as appreciated by those of ordinary skill in the art. For example, C2-6 heteroalkenylene refers to a linear unsaturated divalent hydrocarbon radical of 2 to 6 carbon atoms or a branched unsaturated divalent hydrocarbon radical of 3 to 6 carbon atoms. In certain embodiments, the heteroalkenylene is a linear divalent hydrocarbon radical of 2 to 20 (C2-20), 2 to 15 (C2-15), 2 to 10 (C2-10), or 2 to 6 (C2-6) carbon atoms, or a branched divalent hydrocarbon radical of 3 to 20 (Cs-2o), 3 to 15 (C3-15), 3 to 10 (C3-10), or 3 to 6 (Cs-s) carbon atoms. Examples of heteroalkenylene groups include, but are not limited to, CH=CHO ---, CH=CHOCH2~ -CH-CHCH2O-, -CH=CHS-, -CH=CHSCH2- -CH-CHCH2S-, or -CH=CHCH2NH-.

[0029] The term “alkynyl” refers to a linear or branched monovalent hydrocarbon radical, which contains one or more, in one embodiment, one, two, three, or four, in another embodiment, one, carbon-carbon triple bond(s). An alkynyl group does not contain a carboncarbon double bond. The alkynyl is optionally substituted with one or more substituents Q as described herein. For example, C2-6 alkynyl refers to a linear unsaturated monovalent hydrocarbon radical of 2 to 6 carbon atoms or a branched unsaturated monovalent hydrocarbon radical of 4 to 6 carbon atoms. In certain embodiments, the alkynyl is a linear monovalent hydrocarbon radical of 2 to 20 (CMO), 2 to 15 (C2-15), 2 to 10 (C2-10), or 2 to 6 (C2-6) carbon atoms, or a branched monovalent hydrocarbon radical of 4 to 20 (C4-20), 4 to 15 (C4-15), 4 to 10 (C4-10), or 4 to 6 (C4-6) carbon atoms. Examples of alkynyl groups include, but are not limited to, ethynyl (-OCH), propynyl (including all isomeric forms, e.g, 1-propynyl (-OCCII3) and propargyl (-CH2C=CH)), butynyl (including all isomeric forms, e.g., 1-butyn-l-yl and 2-butyn- 1-yl), pentynyl (including all isomeric forms, e.g., 1-pentyn-l-yl and l-methyl-2-butyn-l-yl), and hexynyl (including all isomeric forms, e.g., 1-hexyn-l-yl and 2-hexyn-l-yl).

[0030] The terms “alkynylene” and “alkynediyl” are used interchangeably herein in reference to a linear or branched divalent hydrocarbon radical, which contains one or more, in one embodiment, one, two, three, or four, in another embodiment, one, carbon-carbon triple bond(s). An alkynylene group does not contain a carbon-carbon double bond. The alkynediyl is optionally substituted with one or more substituents Q as described herein. For example, C2-6alkynediyl refers to a linear unsaturated divalent hydrocarbon radical of 2 to 6 carbon atoms or a branched unsaturated divalent hydrocarbon radical of 4 to 6 carbon atoms. In certain embodiments, the alkynediyl is a linear divalent hydrocarbon radical of 2 to 30 (C2-30), 2 to 20 (C2-20), 2 to 15 (C2-15), 2 to 10 (C2-10), or 2 to 6 (C2-6) carbon atoms, or a branched divalent hydrocarbon radical6) carbon atoms. Examples of alkynediyl groups include, but are not limited to, ethynediyl, propynediyl (including all isomeric forms, e.g, l-propyne-l,3-diyl and l-propyne-3,3-diyl), butynediyl (including all isomeric forms, e.g., 1 -butyne- 1,3 -diyl, 1 -butyne- 1,4-diyl, and 2- butyne- 1,1 -diyl), pentynediyl (including all isomeric forms, e.g., l-pentyne-l,3-diyl, 1-pentyne- 1 ,4-diyl, and 2-pentyne- 1,1 -diyl), and hexynediyl (including all isomeric forms, e.g., 1-hexyne- 1,3-diyl, 1 -hexyne- 1,4-diyl, and 2-hexyne- 1,1 -diyl).

[0031] The terms “heteroalkynylene” and “heteroalkynediyl” are used interchangeably herein in reference to a linear or branched divalent hydrocarbon radical, which contains one or more, in one embodiment, one, two, three, or four, in another embodiment, one, carbon-carbon triple bond(s), and which contains one or more heteroatoms in its main chain, each independently selected from O, S, and N. A heteroalkynylene group does not contain a carbon-carbon double bond. The heteroalkynylene is optionally substituted with one or more substituents Q as described herein. For example, C2-6 heteroalkynylene refers to a linear unsaturated divalent hydrocarbon radical of 2 to 6 carbon atoms or a branched unsaturated divalent hydrocarbon radical of 4 to 6 carbon atoms. In certain embodiments, the heteroalkynylene is a linear divalent hydrocarbon radical of 2 to 30 (C2-30), 2 to 20 (C2-20), 2 to 15 (C2-15), 2 to 10 (C2-10), or 2 to 6 (C2- e) carbon atoms, or a branched divalent hydrocarbon radical of 4 to 30 (C4-30), 4 to 20 (C4-20), 4 to 15 (C4-15), 4 to 10 (C4-10), or 4 to 6 (C4-6) carbon atoms. Examples of heteroalkynylene groups include, but are not limited to, -OCCH2O-, -OCCH2S-, or -C=CCH2NH-

[0032] The term “cycloalkyl” refers to a cyclic monovalent hydrocarbon radical, which is optionally substituted with one or more substituents Q as described herein. In one embodiment, the cycloalkyl is a saturated or unsaturated but non-aromatic, and / or bridged or non-bridged, and / or fused bicyclic group. In certain embodiments, the cycloalkyl has from 3 to 20 (C3-20), from 3 to 15 (C3-15), from 3 to 10 (C3-10), or from 3 to 7 (C3-7) carbon atoms. In one embodiment, the cycloalkyl is monocyclic. In another embodiment, the cycloalkyl is bicyclic. In yet anotherembodiment, the cycloalkyl is tricyclic. In still another embodiment, the cycloalkyl is polycyclic. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptenyl, bicyclofl .1. l]pentyl, bicyclo[2.1. l]hexyl, bicyclo[2.2. l]heptyl, bicyclo[2.2.2]octyl, decalinyl, and adamantyl.

[0033] The terms “cycloalkylene” and “cycloalkanediyl” are used interchangeably herein in reference to a cyclic divalent hydrocarbon radical, which may be optionally substituted with one or more substituents Q as described herein. In one embodiment, cycloalkanediyl groups may be saturated or unsaturated but non-aromatic, and / or bridged, and / or non-bridged, and / or fused bicyclic groups. In certain embodiments, the cycloalkanediyl has from 3 to 30 (C3-30), 3 to 20 (C3-20), from 3 to 15 (C3-15), from 3 to 10 (C3-10), or from 3 to 7 (C3-7) carbon atoms. Examples of cycloalkanediyl groups include, but are not limited to, cyclopropanediyl (including all isomeric forms, e.g., cyclopropane- 1,1 -diyl and cyclopropane- 1,2-diyl), cyclobutanediyl (including all isomeric forms, e.g., cyclobutane- 1,1 -diyl, cyclobutane- 1,2-diyl, and cyclobutane- 1,3-diyl), cyclopentanediyl (including all isomeric forms, e.g., cyclopentane- 1,1 -diyl, cyclopentane- 1,2-diyl, and cyclopentane- 1,3 -diyl), cyclohexanediyl (including all isomeric forms, e.g., cyclohexane- 1, 1 -diyl, cyclohexane- 1,2-diyl, cyclohexane- 1,3 -diyl, and cyclohex-1, 4- diyl), cycloheptanediyl (including all isomeric forms, e.g., cycloheptane- 1,1 -diyl, cycloheptane- 1 ,2-diyl, cycloheptane- 1,3 -diyl, and cycloheptane-l,4-diyl), decalinediyl (including all isomeric forms, e.g., decaline-1,1 -diyl, decaline-1, 2 -diyl, and decaline- 1 ,8-diy I), and adamantdiyl (including all isomeric forms, e.g., adamant- 1,2-diyl, adamant- 1,3 -diyl, and adamant- 1,8-diyl).

[0034] The term “aryl” refers to a monovalent monocyclic aromatic hydrocarbon radical and / or monovalent polycyclic aromatic hydrocarbon radical that contain at least one aromatic carbon ring. In certain embodiments, the aryl has from 6 to 20 (C6-20), from 6 to 15 (C6-15), or from 6 to 10 (C6-10) ring carbon atoms. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, fluorenyl, azulenyl, anthryl, phenanthryl, pyrenyl, biphenyl, and terphenyl. The aryl also refers to bicyclic or tricyclic carbon rings, where one of the rings is aromatic and the others of which may be saturated, partially unsaturated, or aromatic, for example, dihydronaphthyl, indenyl, indanyl, or tetrahydronaphthyl (tetralinyl). In one embodiment, the aiyl is monocyclic. In another embodiment, the aryl is bicyclic. In yet another embodiment, thearyl is tricyclic. In still another embodiment, the aryl is polycyclic. In certain embodiments, the aryl is optionally substituted with one or more substituents Q as described herein.

[0035] The terms “arylene” and “arenediyl” are used interchangeably herein in reference to a divalent monocyclic aromatic hydrocarbon radical or divalent polycyclic aromatic hydrocarbon radical that contains at least one aromatic hydrocarbon ring. In certain embodiments, the arylene has from 6 to 20 (C6-20), from 6 to 15 (C6-15), or from 6 to 10 (Ce-io) ring atoms. Examples of arylene groups include, but are not limited to, phenylene (including ail isomeric forms, e.g., phen-l,2-diyl, phen- 1,3 -diyl, and phen-l,4-diyl), naphthylene (including all isomeric forms, e.g., naphth-1 ,2-diyl, naphth-l,3-diyl, and naphth- 1,8-diyl), fluorenylene (including all isomeric forms, e.g, fluoren-l,2-diyl, fluoren-l,3-diyl, and fluoren- 1,8-diyl), azulenylene (including all isomeric forms, e.g, azulen-l,2-diyl, azulen- 1,3 -diyl, and azulen-1 ,8- diyl), anthrylene (including all isomeric forms, e.g., anthr-l,2-diyl, anthr- 1,3 -diyl, and anthr-1,8- diyl), phenanthrylene (including all isomeric forms, e.g., phenanthr-l,2-diyl, phenanthr-l,3-diyl, and phenanthr- 1,8-diyl), pyrenylene (including all isomeric forms, e.g., pyren-l,2-diyl, pyren- 1,3-diyl, and pyren- 1,8-diyl), biphenylene (including all isomeric forms, e.g., biphen-2,3-diyl, biphen-3,4’-diyl, and biphen-4,4’-diyl), and terphenylene (including all isomeric forms, e.g., terphen-2,3-diyl, terphen-3,4’-diyl, and terphen-4,4’-diyl). Arylene also refers to bicyclic or tricyclic carbon rings, where one of the rings is aromatic and the others of which may be saturated, partially unsaturated, or aromatic, for example, dihydronaphthylene (including all isomeric forms, e.g., dihydronaphth- 1 ,2-diyl and dihydronaphth- 1,8-diyl), indenylene (including all isomeric forms, e.g., inden- 1 ,2-diyl, inden- 1 ,5-diyl, and inden-l,7-diyl), indanylene (including all isomeric forms, e.g, indan- 1 ,2-diyl, indan-1 ,5-diyl, and indan- 1,7-diyl), or tetrahydronaphthylene (tetralinyl ene) (including all isomeric forms, e.g, tetrahydronaphth- 1,2- diyl, tetrahydronaphth-l,5-diyl, and tetrahydronaphth- 1,8-diyl). In certain embodiments, arylene is optionally substituted with one or more substituents Q as described herein.

[0036] The term “aralkyl” or “arylalkyl” refers to a monovalent alkyl group substituted with one or more aryl groups. In certain embodiments, the aralkyl has from 7 to 30 (C7-30), from 7 to 20 (C7-20), or from 7 to 16 (C7-16) carbon atoms. Examples of aralkyl groups include, but are not limited to, benzyl, phenyl ethyl (including all isomeric forms, e.g., 1 -phenylethyl and 2- phenylethyl), and phenylpropyl (including all isomeric forms, e.g., 1 -phenyl propyl, 2-phenylpropyl, and 3 -phenyl propyl). In certain embodiments, the aralkyl is optionally substituted with one or more substituents Q as described herein.

[0037] The term “aralkylene” or “arylalkylene” refers to a divalent alkyl group substituted with one or more aryl groups. In certain embodiments, the aralkylene has from 7 to 30 (C7-30), from 7 to 20 (C7-20), or from 7 to 16 (C7-16) carbon atoms. Examples of aralkylene groups include, but are not limited to, benzylene (including all isomeric forms, e.g., phenylmethdiyl), phenyl ethylene (including all isomeric forms, e.g., 2-phenyl-ethan- 1,1 -diyl and 2-phenyl-ethan-l,2-diyl), and phenylpropylene (including all isomeric forms, e.g., 3-phenyl- propan- 1,1 -diyl, 3-phenyl-propan-l,2-diyl, and 3-phenyl-propan-l,3-diyl). In certain embodiments, the aralkylene is optionally substituted with one or more substituents Q as described herein.

[0038] The term “heteroaryl” refers to a monovalent monocyclic aromatic group or monovalent polycyclic aromatic group that contain at least one aromatic ring, wherein at least one aromatic ring contains one or more heteroatom s, each independently selected from O, S, and N, in the ring. For a heteroaryl group containing a heteroaromatic ring and a nonaromatic heterocyclic ring, the heteroaryl group is not bonded to the rest of a molecule through its nonaromatic heterocyclic ring. Each ring of a heteroaryl group can contain one or two O atoms, one or two S atoms, and / or one to four N atoms; provided that the total number of heteroatoms in each ring is four or less and each ring contains at least one carbon atom. In certain embodiments, the heteroaryl has from 5 to 20, from 5 to 15, or from 5 to 10 ring atoms. In one embodiment, the heteroaryl is monocyclic. Examples of monocyclic heteroaryl groups include, but are not limited to, furanyl, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, thiadiazolyl, thiazolyl, thienyl, tetrazolyl, triazinyl, and triazolyl. In another embodiment, the heteroaryl is bicyclic. Examples of bicyclic heteroaryl groups include, but are not limited to, benzofuranyl, benzimidazolyl, benzoisoxazolyl, benzopyranyl, benzothiadi azolyl, benzothiazolyl, benzothienyl, benzotriazolyl, benzoxazolyl, furopyrindyl (including all isomeric forms, e.g., furo[2,3-£>]pyridinyl, furo[2,3-c]pyridinyl, furo[3,2-Z>]pyridinyl, furo[3,2-c]pyridinyl, furo[3,4-Z>]pyridinyl, and furo[3,4-c]pyridinyl), imidazopyridinyl (including all isomeric forms, e.g., imidazo[l,2-a]pyridinyl, imidazo[4,5- Z>]pyridinyl, and imidazo[4,5-c]pyridinyl), imidazothiazolyl (including all isomeric forms, e.g.,imidazo[2, 1-Z>]thiazolyl and imidazo[4,5-< / |thiazolyl), indazolyl, indolizinyl, indolyl, isobenzofuranyl, isobenzothienyl (i.e., benzo[c]thienyl), isoindolyl, isoquinolinyl, naphthyridinyl (including all isomeric forms, e.g., 1,5 -naphthyridinyl, 1,6-naphthyridinyl, 1,7-naphthyridinyl, and 1,8-naphthyridinyl), oxazolopyridinyl (including all isomeric forms, e.g., oxazolo[4,5- d]pyridinyl, oxazolo[4,5-c]pyridinyl, oxazolo[5,4-ft]pyridinyl, and oxazolo[5,4-c]pyridinyl), phthalazinyl, pteridinyl, purinyl, pyrrolopyridyl (including all isomeric forms, e.g., pyrrolo[2,3- / ?]pyridinyl, pyrrolo[2,3-c]pyridinyl, pyrrol o[3,2-Z>]pyridinyl, and pyrrolo[3,2-c]pyridinyl), quinolinyl, quinoxalinyl, quinazolinyl, thiadiazolopyrimidyl (including all isomeric forms, e.g., [I,2,5]thiadiazolo[3,4-t7]pyrimidinyl and [ l,2,3]thiadiazolo[4,5-<i]pyrimidinyl), and thienopyridyl (including all isomeric forms, e.g, thieno[2,3-5]pyridinyl, thieno[2,3-c]pyridinyl, thieno[3,2- / >]pyridinyl, and thieno[3,2-c]pyridinyl). In yet another embodiment, the heteroaryl is tricyclic. Examples of tricyclic heteroaryl groups include, but are not limited to, acridinyl, benzindolyl, carbazolyl, dibenzofuranyl, perimidinyl, phenanthrolinyl, phenanthridinyl (including all isomeric forms, e.g., 1,5-phenanthrolinyl, 1,6-phenanthrolinyl, 1,7- phenanthrolinyl, 1,9-phenanthrolinyl, and 2,10-phenanthrolinyl), phenarsazinyl, phenazinyl, phenothiazinyl, phenoxazinyl, and xanthenyl. In certain embodiments, the heteroaryl is optionally substituted with one or more substituents Q as described herein.

[0039] The terms “heteroarylene” and “heteroarenediyl” are used interchangeably herein in reference to a divalent monocyclic aromatic group or divalent polycyclic aromatic group that contains at least one aromatic ring, wherein at least one aromatic ring contains one or more heteroatoms in the ring, each of which is independently selected from 0, S, and N. For a heteroarylene group containing a heteroaromatic ring and a nonaromatic heterocyclic ring, the heteroarylene group is not bonded to the rest of a molecule via its nonaromatic heterocyclic ring. Each ring of a heteroarylene group can contain one or two 0 atoms, one or two S atoms, and / or one to four N atoms, provided that the total number of heteroatoms in each ring is four or less and each ring contains at least one carbon atom. In certain embodiments, the heteroarylene has from 5 to 20, from 5 to 15, or from 5 to 10 ring atoms. Examples of monocyclic heteroarylene groups include, but are not limited to, furandiyl, imidazoldiyl, isothiazoldiyl, isoxazoldiyl, oxadiazoldiyl, oxazoldiyl, pyrazindiyl, pyrazoldiyl, pyridazindiyl, pyridindiyl, pyrimidindiyl, pyrrol diyl, thiadiazol diyl, thiazoldiyl, thiendiyl, tetrazol diyl, triazinediyl, and triazol diyl. Examples of bicyclic heteroarylene groups include, but are not limited to, benzofuran diyl,benzimidazoldiyl, benzoisoxazoldiyl, benzopyrandiyl, benzothiadiazoldiyl, benzothiazoldiyl, benzothiendiyl, benzotriazoldiyl, benzoxazoldiyl, furopyridindiyl (including all isomeric forms, e.g, furo[2,3-Z>]pyridindiyl, furo[2,3-c]pyridindiyl, furo[3,2- / >]pyridindiyl, furo[3,2-c]- pyridindiyl, furo[3,4-Z>]pyridindiyl, and furo[3,4-c]pyridindiyl), imidazopyridindiyl (including all isomeric forms, e.g, imidazo[l,2-a]pyridindiyl, imidazo[4,5-&]pyridindiyl, and imidazo[4,5-c]- pyridindiyl), imidazothiazoldiyl (including all isomeric forms, e.g, imidazo[2,l-5]thiazoldiyl and imidazo[4,5-< / ]thiazoldiyl), indazoldiyl, indolizindiyl, indoldiyl, isobenzofurandiyl, isobenzothiendiyl (z.e., benzo[c]thiendiyl), i soindoldiyl, isoquinolindiyl, naphthyridindiyl (including all isomeric forms, e.g., 1,5-naphthyridindiyl, 1,6-naphthyridindiyl, 1,7- naphthyridindiyl, and 1,8-naphthyridindiyl), oxazolopyridindiyl (including all isomeric forms, e.g., oxazolo[4,5-Z>]pyridindiyl, oxazolo[4,5-c]pyridindiyl, oxazolo[5,4- / >]pyridindiyl, and oxazolo[5,4-c]pyridindiyl), phthalazindiyl, pteridindiyl, purindiyl, pyrrolopyridindiyl (including all isomeric forms, e.g., pyrrolo[2,3-i]pyridindiyl, pyrrolo[2,3-c]pyridindiyl, pyrrolo[3,2-5]- pyridindiyl, and pyrrolo[3,2-c]pyridindiyl), quinolindiyl, quinoxalindiyl, quinazolindiyl, thiadiazolopyrimidindiyl (including all isomeric forms, e.g., [l,2,5]thiadiazolo[3,4-c / ]- pyrimidindiyl and [l,2,3]thiadiazolo[4,5-d]pyrimidindiyl), and thienopyridindiyl (including all isomeric forms, e.g., thieno[2,3- / >]pyridindiyl, thieno[2,3-c]pyridindiyl, thieno[3,2-d]pyridindiyl, and thieno[3,2-c]pyridindiyl). Examples of tricyclic heteroarylene groups include, but are not limited to, acridindiyl , benzindoldiyl, carbazoldiyl, dibenzofurandiyl, perimidindiyl, phenanthrolindiyl (including all isomeric forms, e.g., 1,5-phenanthrolindiyl, 1,6- phenanthrolindiyl, 1,7-phenanthrolindiyl, 1,9-phenanthrolindiyl, and 2,10-phenanthrolindiyl), phenanthridindiyl, phenarsazindiyl, phenazindiyl, phenothiazindiyl, phenoxazindiyl, and xanthendiyl. In certain embodiments, heteroaiylene is optionally substituted with one or more substituents Q as described herein.

[0040] The term “heterocyclyl” or “heterocyclic” refers to a monovalent monocyclic non-aromatic ring system or monovalent polycyclic ring system that contains at least one nonaromatic ring, wherein one or more of the non-aromatic ring atoms are heteroatoms, each independently selected from 0, S, and N; and the remaining ring atoms are carbon atoms. For a heterocyclyl group containing a heteroaromatic ring and a nonaromatic heterocyclic ring, the heterocyclyl group is not bonded to the rest of a molecule through the heteroaromatic ring. In certain embodiments, the heterocyclyl or heterocyclic group has from 3 to 20, from 3 to 15, from3 to 10, from 3 to 8, from 4 to 7, or from 5 to 6 ring atoms. In certain embodiments, the heterocyclyl is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may be fused or bridged, and in which nitrogen or sulfur atoms may be optionally oxidized, nitrogen atoms may be optionally quaternized, and some rings may be partially or fully saturated, or aromatic. The heterocyclyl may be attached to the main structure at any heteroatom or carbon atom which results in the creation of a stable compound. Examples of heterocyclyls and heterocyclic groups include, but are not limited to, azepinyl, benzodioxanyl, benzodioxolyl, benzofuranonyl, chromanyl, decahydroisoquinolinyl, di hydrobenzofuranyl, dihydrobenzisothiazolyl, dihydro- benzisoxazinyl (including all isomeric forms, e.g., l,4-dihydrobenzo[t / ][l,3]oxazinyl, 3,4- dihydrobenzo[c][l,2]-oxazinyl, and 3,4-dihydrobenzo[<7][l,2]oxazinyl), dihydrobenzothienyl, dihydroisobenzofuranyl, dihydrobenzo[c]thienyl, dihydrofuryl, dihydroisoindolyl, dihydropyranyl, dihydropyrazolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dioxolanyl, 1,4-dithianyl, furanonyl, imidazolidinyl, imidazolinyl, indolinyl, isochromanyl, isoindolinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, oxazolidinonyl, oxazolidinyl, oxiranyl, piperazinyl, piperidinyl, 4- piperidonyl, pyrazolidinyl, pyrazolinyl, pyrrolidinyl, pyrrolinyl, quinuclidinyl, tetrahydrofuryl, tetrahydroisoquinolinyl, tetrahydropyranyl, tetrahydrothienyl, thiamorpholinyl, thiazolidinyl, thiochromanyl, tetrahydroquinolinyl, and 1 ,3,5-trithianyl. In certain embodiments, the heterocyclyl is optionally substituted with one or more substituents Q as described herein.

[0041] The term “heterocyclylene” refers to a divalent monocyclic non-aromatic ring system or divalent polycyclic ring system that contains at least one non-aromatic ring, wherein one or more of the non-aromatic ring atoms are heteroatoms independently selected from 0, S, and N; and the remaining ring atoms are carbon atoms. For a heterocyclylene group containing a heteroaromatic ring and a nonaromatic heterocyclic ring, the heterocyclylene group has at least one bond to the rest of a molecule via its nonaromatic heterocyclic ring. In certain embodiments, the heterocyclylene group has from 3 to 20, from 3 to 15, from 3 to 10, from 3 to 8, from 4 to 7, or from 5 to 6 ring atoms. In certain embodiments, the heterocyclylene is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may be fused or bridged, and in which nitrogen or sulfur atoms may be optionally oxidized, nitrogen atoms may be optionally quaternized, and some rings may be partially or fully saturated, or aromatic. The heterocyclylene may be attached to the main structure at any heteroatom or carbon atom which results in the creation of a stablecompound. Examples of such heterocyclylene groups include, but are not limited to, azepindiyl, benzodioxandiyl, benzodioxoldiyl, benzofuranondiyl, chromandiyl, decahydroisoquinolindiyl, dihydrobenzofurandiyl, dihydrobenzisothiazoldiyl, dihydrobenzisoxazindiyl (including all isomeric forms, e.g., l,4-dihydrobenzo[J][l,3]oxazindiyl, 3,4-dihydrobenzo[c][l,2]oxazindiyl, and 3,4-dihydrobenzo[tf][l,2]oxazindiyl), dihydrobenzothiendiyl, dihydroisobenzofurandiyl, dihydrobenzo[c]thiendiyl, dihydrofurdiyl, dihydroisoindoldiyl, dihydropyrandiyl, dihydropyrazoldiyl, dihydropyrazindiyl, dihydropyridindiyl, dihydropyrimidindiyl, di hydropyrrol diyl, dioxolandiyl, 1 ,4-dithiandiyl, furanondiyl, imidazolidindiyl, imidazolindiyl, indolindiyl, isochromandiyl, isoindolindiyl, isothiazolidindiyl, isoxazolidindiyl, morpholindiyl, octahydroindoldiyl, octahydroisoindoldiyl, oxazolidinondiyl, oxazolidindiyl, oxirandiyl, piperazindiyl, piperidindiyl, 4-piperidondiyl, pyrazolidindiyl, pyrazolindiyl, pyrrolidindiyl, pyrrolindiyl, quinuclidindiyl, tetrahydrofurdiyl, tetrahydroisoquinolindiyl, tetrahydropyrandiyl, tetrahydrothiendiyl, thiamorpholindiyl, thiazolidindiyl, thiochromandiyl, tetrahydroquinolindiyl, and 1 ,3,5-trithiandiyl. In certain embodiments, the heterocyclylene is optionally substituted with one or more substituents Q as described herein.

[0042] The term “halogen,” “halide,” or “halo” refers to fluoro, chloro, bromo, and / or iodo.

[0043] The term “optionally substituted” is intended to mean that a group or substituent, such as an alkyl, alkylene, heteroalkyl, heteroalkylene, alkenyl, alkenylene, heteroalkenylene, alkynyl, alkynylene, heteroalkynylene, cycloalkyl, cycloalkylene, aryl, arylene, aralkyl, aralkylene, heteroaryl, heteroarylene, heterocyclyl, or heterocyclylene group, may be substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, each of which is independently selected from, e.g., (a) deuterium (-D), cyano (-CN), halo, imino (=NH), nitro (-NO?.), and oxo (=O); (b) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C&-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; and (c) -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -C(O)SRa, -C(NRa)NRbRc, -C(S)Ra, -C(S)ORa, -C(S)NRbRc, -ORa, OC(O)Ra, -OC(O)ORa, -OC(O)NRbRc, -OC(O)SRa, -OC(NRa)NRbRc, -OC(S)Ra, -OC(S)ORa, -OC(S)NRbRc, -OP(O)(ORb)ORc, -OS(O)Ra, ~OS(O)2.Ra, -OS(O)NRbRc, ~OS(O)2NRbRc, ~NRbRc, -NRaC(0)Rd, -NRaC(0)0Rd, ~NRaC(0)NRbRc,-NRaC(O)SRd, -NRaC(NRd)NRbRc, -NRaC(S)Rd, --NRaC(S)ORd, -NRaC(S)NRbRc, -NRaS(O)Rd, -NRaS(O)2Rd, -NRaS(O)NRbRc, -NRaS(O)2NRbRc, -SRa, -S(O)Ra, -S(O)2Ra, S(O)NRbRc, and ---S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rdis independently (i) hydrogen or deuterium; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; or (iii) Rband Rctogether with the N atom to which they are attached form heterocyclyl optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa. As used herein, all groups that can be substituted are “optionally substituted.”

[0044] In one embodiment, each Qais independently selected from: (a) deuterium, cyano, halo, imino, nitro, and oxo, (b) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Cs-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl; and (c) -C(O)Re, -C(O)ORe, -C(O)NRfRg, -C(O)SRe, ~C(NRe)NRfR8, -C(S)Re, -C(S)ORe, ~C(S)NRfR®, -ORe, -OC(O)Re, -OC(O)ORe, -OC(O)NRfRg, -OC(O)SRe, ~OC(NRe)NRfRg, ~OC(S)Re, -OC(S)ORe, -OC(S)NRfRg, -OP(O)(ORf)ORg, -OS(O)Re, ~OS(O)2Re, -OS(O)NRfRg, -OS(O)2NRfRg, -NRfRg, -NReC(O)Rh, -NReC(O)ORf, -NReC(O)NRfRg, -NReC(O)SRf, -NReC(NRh)NRfRg, -NReC(S)Rh, -NReC(S)ORf, -NReC(S)NRfRg, -NReS(O)Rh, -NReS(O)2Rh, -NReS(O)NRfRg, -NReS(O)2NRfRs, -SRe, -S(O)Re, -S(O)2Re, -S(O)NRfRg, and -S(O)2NRtRg; wherein each Re, Rf, R8, and Rhis independently (i) hydrogen or deuterium; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) R1and R8together with the N atom to which they are attached form heterocyclyl.

[0045] In certain embodiments, “optically active” and ’’enantiomerically active” refer to a collection of molecules, which has an enantiomeric excess of no less than about 80%, no less than about 90%, no less than about 91%, no less than about 92%, no less than about 93%, no less than about 94%, no less than about 95%, no less than about 96%, no less than about 97%, no less than about 98%, no less than about 99%, no less than about 99.5%, or no less than about 99.8%.In certain embodiments, an optically active compound comprises about 95% or more of one enantiomer and about 5% or less of the other enantiomer based on the total weight of the enantiomeric mixture in question. In certain embodiments, an optically active compound comprises about 98% or more of one enantiomer and about 2% or less of the other enantiomerbased on the total weight of the enantiomeric mixture in question. In certain embodiments, an optically active compound comprises about 99% or more of one enantiomer and about 1% or less of the other enantiomer based on the total weight of the enantiomeric mixture in question.

[0046] In describing an optically active compound, the prefixes J? and 5 are used to denote the absolute configuration of the compound about its chiral center(s). The (+) and (-) are used to denote the optical rotation of the compound, that is, the direction in which a plane of polarized light is rotated by the optically active compound. The (-) prefix indicates that the compound is levorotatory, that is, the compound rotates the plane of polarized light to the left or counterclockwise. The (+) prefix indicates that the compound is dextrorotatory, that is, the compound rotates the plane of polarized light to the right or clockwise. However, the sign of optical rotation, (+) and (-), is not related to the absolute configuration of the compound, R and .S',

[0047] The term “i sotopically enriched” refers to a compound that contains an unnatural proportion of an isotope at one or more of the atoms that constitute such a compound. In certain embodiments, an isotopically enriched compound contains unnatural proportions of one or more isotopes, including, but not limited to, hydrogen (3H), deuterium (2H), tritium (3H), carbon- 11 (nC), carbon-12 (12C), carbon-13 (13C), carbon-14 (i4C), nitrogen-13 (13N), nitrogen-14 (14N), nitrogen-15 (!5N), oxygen-14 (14O), oxygen-15 (15O), oxygen-16 (16O), oxygen-17 (! 7O), oxygen-18 (18O), fluorine-17 (b'F), fluorine-18 (18F), phosphorus-31 (31P), phosphorus-32 (32P), phosphorus-33 (33P), sulfur-32 (32S), sulfur-33 (33S), sulfur-34 (34S), sulfur-35 (35S), sulfur-36 (3oS), chlorine-35 (j5Cl), chlorine-36 (3oCl), chlorine-37 (37C1), bromine-79 (79Br), bromine-81 (81Br), iodine-123 (123I), iodine-125 (125I), iodine-127 (127I), iodine-129 (129I), and iodine-131 (131I). In certain embodiments, an isotopically enriched compound is in a stable form, that is, non-radioactive. In certain embodiments, an isotopically enriched compound contains unnatural proportions of one or more isotopes, including, but not limited to, hydrogen (3H), deuterium (2H), carbon- 12 (12C), carbon- 13 (ljC), nitrogen- 14 (14N), nitrogen- 15 (15N), oxygen- 16 (16O), oxygen-17 (17O), oxygen-18 (18O), fluorine-17 (17F), phosphorus-31 (51P), sulfur-32 (32S), sulfur- 33 (JJS), sulfur-34 (34S), sulfur-36 (3oS), chlorine-35 (J3C1), chlorine-37 (3 / Cl), bromine-79 ( / 9Br), bromine-81 (81Br), and iodine-127 (127I). In certain embodiments, an isotopically enriched compound is in an unstable form, that is, radioactive. In certain embodiments, an isotopically enriched compound contains unnatural proportions of one or more isotopes,including, but not limited to, tritium (3H), carbon-1 1 (nC), carbon-14 (14C), nitrogen-13 (nN), oxygen-14 (14O), oxygen-15 (15O), fluorine-18 (18F), phosphorus-32 (j2P), phosphorus-33 (33P), sulfur-35 (35S), chlorine-36 (3bCl), iodine-123 (123I), iodine-125 (125I), iodine-129 (129I), and iodine- 131 (131I). It will be understood that, in a compound as provided herein, any hydrogen can be2H, as example, or any carbon can bel3C, as example, or any nitrogen can bel5N, as example, or any oxygen can be1SO, as example, where feasible according to the judgment of one of ordinary skill in the art.

[0048] The term “isotopic enrichment” refers to the percentage of incorporation of a less prevalent isotope (e.g., D for deuterium or hydrogen-2) of an element at a given position in a molecule in the place of a more prevalent isotope (e.g,3H for protium or hydrogen-1) of the element. As used herein, when an atom at a particular position in a molecule is designated as a particular less prevalent isotope, it is understood that the abundance of that isotope at that position is substantially greater than its natural abundance.

[0049] The term “isotopic enrichment factor” refers the ratio between the isotopic abundance in an isotopically enriched compound and the natural abundance of a specific isotope.

[0050] The term “hydrogen” or the symbol “H” refers to the composition of naturally occurring hydrogen isotopes, which include protium (3H), deuterium (2H or D), and tritium (3H), in their natural abundances. Protium is the most common hydrogen isotope having a natural abundance of more than 99.98%. Deuterium is a less prevalent hydrogen isotope having a natural abundance of about 0.0156%.

[0051] The term “deuterium enrichment” refers to the percentage of incorporation of deuterium at a given position in a molecule in the place of hydrogen. For example, deuterium enrichment of 1% at a given position means that 1% of molecules in a given sample contain deuterium at the specified position. Because the naturally occurring distribution of deuterium is about 0.0156% on average, deuterium enrichment at any position in a compound synthesized using non-enriched starting materials is about 0.0156% on average. As used herein, when a particular position in an isotopically enriched compound is designated as having deuterium, it is understood that the abundance of deuterium at that position in the compound is substantially greater than its natural abundance (0.0156%).

[0052] The term “carbon” or the symbol “C” refers to the composition of naturally occurring carbon isotopes, which include carbon-12 (12C) and carbon-13 (13C) in their natural abundances. Carbon-12 is the most common carbon isotope having a natural abundance of more than 98.89%. Carbon-13 is a less prevalent carbon isotope having a natural abundance of about 1.11%.

[0053] The term “carbon-13 enrichment” or “13C enrichment” refers to the percentage of incorporation of carbon- 13 at a given position in a molecule in the place of carbon. For example, carbon- 13 enrichment of 10% at a given position means that 10% of molecules in a given sample contain carbon-13 at the specified position. Because the naturally occurring distribution of carbon-13 is about 1.11% on average, carbon-13 enrichment at any position in a compound synthesized using non-enriched starting materials is about 1.11% on average. As used herein, when a particular position in an isotopically enriched compound is designated as having carbon- 13, it is understood that the abundance of carbon-13 at that position in the compound is substantially greater than its natural abundance (1.11%).

[0054] The terms “substantially pure” and “substantially homogeneous” mean, when referred to a substance, sufficiently homogeneous to appear free of readily detectable impurities as determined by a standard analytical method used by one of ordinary skill in the art, including, but not limited to, thin layer chromatography (TLC), gel electrophoresis, high performance liquid chromatography (HPLC), gas chromatography (GC), nuclear magnetic resonance (NMR), and mass spectrometry (MS); or sufficiently pure such that further purification would not detectably alter the physical, chemical, biological, and / or pharmacological properties, such as enzymatic and biological activities, of the substance. In certain embodiments, “substantially pure” or “substantially homogeneous” refers to a collection of molecules, wherein at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 99.5% by weight of the molecules are a single compound, including a single enantiomer, a racemic mixture, or a mixture of enantiomers, as determined by standard analytical methods. As used herein, when an atom at a particular position in an isotopically enriched molecule is designated as a particular less prevalent isotope, a molecule that contains other than the designated isotope at the specified position is an impurity with respect to the isotopically enriched compound. Thus, for a deuterated compound that has an atom at a particular positiondesignated as deuterium, a compound that contains a protium at the same position is an impurity.

[0055] The term “solvate” refers to a complex or aggregate formed by one or more molecules of a solute, e.g., a compound provided herein, and one or more molecules of a solvent, which are present in a stoichiometric or non-stoichiometric amount. Suitable solvents include, but are not limited to, water, methanol, ethanol, n-propanol, isopropanol, and acetic acid. In certain embodiments, the solvent is pharmaceutically acceptable. In one embodiment, the complex or aggregate is in a crystalline form. In another embodiment, the complex or aggregate is in a noncrystalline form. Where the solvent is water, the solvate is a hydrate. Examples of hydrates include, but are not limited to, a hemihydrate, monohydrate, dihydrate, trihydrate, tetrahydrate, and pentahydrate.

[0056] For a divalent group described herein, no orientation is implied by the direction in which the divalent group is presented. For example, unless a particular orientation is specified, the formula ~C(O)NH~ represents both -C(O)NH~ and -NHC(O)-.

[0057] The phrase “an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautom ers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof’ has the same meaning as the phrase “(i) an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant of the compound referenced therein; (ii) a pharmaceutically acceptable salt, solvate, hydrate, or prodrug of the compound referenced therein; or (iii) a pharmaceutically acceptable salt, solvate, hydrate, or prodrug of an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more di astereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant of the compound referenced therein.”Compounds

[0058] In one embodiment, provided herein is a compound of Formula (I):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein:A is a bond, heterocyclylene, or -S(O2)-;E is C6-14 arylene, heteroarylene, or heterocyclylene;L is a linker;X is a bond or -C(O)-;R1is (i) hydrogen; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Cs-u and, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii ) -C(O)Rla, C(O)ORla, -C(O)NRlbRlc, -C(O)SRla, -C(NRia)NRlbRlc, -C(S)Rla, -C(S)ORla, -C(S)NRlbRlc, -S(O)Rla, -S(O)2Rla, -S(O)NRlbRlc, or -S(O)2NRlbRlc;R2, R', and R4are each independently (i) hydrogen, deuterium, cyano, halo, or nitro; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) -C(O)Rla, -C(O)ORla, -C(O)NRlbRlc, -C(O)SRla, -C(NRla)NRlbRlc, -C(S)Rla, -C(S)ORla, -C(S)NRlbRlc, -ORla, -OC(O)Rla, -OC(O)ORla, -OC(O)NRlbRlc, -OC(O)SRla, ~OC(NRla)NRlbRlc, -OC(S)Rla, -OC(S)ORla, -OC(S)NRlbRlc, -OS(O)Rla, -OS(O)2Ria, -OS(O)NRlbRlc, -OS(O)2NRlbRlc, -NRlbRlc, -NRlaC(O)Rld, -NRlaC(O)ORld, -NRlaC(O)NRlbRlc, -NRlaC(O)SRld, -NRlaC(NRld)NRlbRlc, -NRlaC(S)Rld, -NRlaC(S)ORld, -NRlaC(S)NRlbRlc, -NRlaS(O)Rld, -NRlaS(0)2Rld, -NRlaS(O)NRlbRlc, -NRlaS(O)2NRlbRlc, -SRla, -S(O)Rla, -S(O)2Rla, -S(O)NRlbRlc, or -S(O)2NRlbRlc;REis:wherein: each AEis independently a bond, -O-, -N(Rlb)-, -S-, C1-6 alkylene, Ci-6 heteroalkylene, C2-6 alkenylene, C2-6 heteroalkenyl ene, C2-6 alkynylene, C2-6 heteroalkynylene, C3-10 cycloalkylene, Ce-14 arylene, C7-15 aralkylene, heteroarylene, heterocyclylene, Ci-e heteroalkylene-C6-i4 arylene, Ci-e heteroalkylene-heterocyclylene, or C2-6 alkynylene-heterocyclylene; each XEis independently C(RE1) or N;YEis a bond, C1-6 alkylene, -0- -S-, -S(0)-, -S(02)-, or -N(RE3)-;Z is -CH2- or -C(0)-; one of Z1, Z2, Z3, and Z4is ~C= and the remaining three of Zl, Z2, Z3, and Z4are each independently -C(RE4a):::; or Z1is a bond; one of Z2, Z3,and the remaining two of Z2, Z3, and Z4are each independently -C(RE4a)= or -S-; each RE1is independently hydrogen, deuterium, halo, or C1-6 alkyl; each RE2, RE3, and RE3is independently hydrogen or C1-6 alkyl; each RE4is independently (i) deuterium, cyano, halo, or nitro; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) -C(0)Rla, -C(0)0Rla, -C(0)NRlbRlc, -C(O)SRla, -C(NRla)NRlbRlc, -C(S)Rla, -C(S)ORla, -C(S)NRlbRlc, -0Rla, -0C(0)Rla, -0C(0)0Rla, -0C(0)NRlbRlc, -OC(O)SRla, ~0C(NRla)NRibRlc, -OC(S)Ria, -OC(S)ORla, -0C(S)NRlbRlc, -OS(O)Rla, -OS(O)2Rla, -0S(0)NRlbRlc, -0S(0)2NRlbRlc, -NRibRlc, ~NRlaC(0)Rld, -NRlaC(0)0Rld, -NRlaC(0)NRlbRlc, ~NRlaC(0)SRld, -NRlaC(NRld)NRlbRlc, -NRlaC(S)Rld, -NRlaC(S)0Rld, -NRlaC(S)NRlbRlc, -NRlaS(0)Rld, -NRlaS(0)2Rld, - NRlaS(0)NRlbRlc, -NRlaS(0)zNRlbRlc, -SRla, -S(O)Rla, -S(O)2Rla, -S(0)NRlbRlc, or -S(0)2NRlbRlc; each RE4ais independently hydrogen or RE4; each m is independently an integer of 0, 1, or 2; and each n is independently an integer of 0, 1, 2, or 3; andeach Rla, Rlb, Rlc, and Rldis independently hydrogen, deuterium, C1-6 alkyl, Ci-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-14 aryl, C--15 aralkyl, heteroaryl, or heterocyclyl; wherein each alkyl, alkylene, heteroalkyl, heteroalkylene, alkenyl, alkenylene, heteroalkenylene, alkynyl, alkynylene, heteroalkynylene, cycloalkyl, cycloalkylene, aryl, arylene, aralkyl, aralkylene, heteroaryl, heteroarylene, heterocyclyl, and heterocyclylene is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, wherein each Q is independently selected from: (a) deuterium, cyano, halo, imino, nitro, and oxo; (b) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-14 and, C7-15 aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; and (c) -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -C(O)SRa, ~C(NRa)NRbRc, -C(S)Ra, -C(S)ORa, -C(S)NRbRc, -ORa, -OC(O)Ra, -OC(O)ORa, -OC(O)NRbRc, -OC(O)SRa, -OC(NRa)NRbRc, -OC(S)Ra, -OC(S)ORa, -OC(S)NRbRc, -OP(O)(ORb)ORc, -OS(O)Ra, ~OS(O)2Ra, -OS(O)NRbRc, -OS(O)2NRbRc, -NRbRc, -NRaC(O)Rd, ~NRaC(O)ORd, -NRaC(O)NRbRc, -NRaC(O)SRd, -NRaC(NRd)NRbRc, -NRaC(S)Rd, -NRaC(S)ORd, -NRaC(S)NRbRc, -NRaS(O)Rd, -NRaS(O)2Rd, -NRaS(O)NRbRc, -NRaS(O)2NRbRc, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRbRc, and - S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rdis independently (i) hydrogen or deuterium; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; or (iii) Rband Rctogether with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; wherein each Qais independently selected from: (a) deuterium, cyano, halo, nitro, imino, and oxo; (b) C1-6 alkyl, C 1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl; and (c) -C(O)Re, -C(O)ORe, -C(O)NRfRs, C(O)SR' , -C(NRe)NRfRg, -C(S)Re, -C(S)ORe, -C(S)NRfRg, -ORe, -OC(O)Re, -OC(O)ORe, -OC(O)NRfRg, OC(O)SRe, -OC(NRe)NRfR8, -OC(S)Re, -OC(S)ORe, -OC(S)NRfRg, -OP(O)(ORf)ORg, -OS(O)Re, -OS(O)2Re, -OS(O)NRfRg, -OS(O)2NRfRg, -NRfRg, -NReC(O)Rh, -NReC(O)ORf, -NReC(O)NRfRg, -NReC(O)SRf, -NReC(NRh)NRfRg, -NReC(S)Rh, -NReC(S)ORf, -NReC(S)NRfRg, -NReS(O)Rh, -NReS(O)2Rb, -NReS(O)NRfRs,-NReS(O)2NRfRs, -SRe, -S(O)Re, -S(O)2Re, -S(O)NRfRg, and -S(O)2NRfRg; wherein each Re, R\ Rg, and Rhis independently (i) hydrogen or deuterium, (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) Rfand R8together with the N atom to which they are attached form heterocyclyl.

[0059] In certain embodiments, in Formula (I), E is Cs-i4 arylene, optionally substituted with one or more substituents Q. In certain embodiments, in Formula (I), E is phenylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is phen-l,4-diy, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is bicyclic Cs-14 arylene, optionally substituted with one, two, or three substituents Q.

[0060] In certain embodiments, in Formula (I), E is heteroarylene, optionally substituted with one or more substituents Q In certain embodiments, in Formula (I), E is monocyclic heteroarylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is 5-, 6-, or 7-membered heteroarylene, each optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is 5-membered heteroarylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is 6-membered heteroarylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is pyridindiyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is pyridine-2, 5-diyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is 7-membered heteroarylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is bicyclic heteroarylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is 5,5-, 5,6-, or 6,6-fused heteroarylene, each optionally substituted with one, two, or three substituents Q.

[0061] In certain embodiments, in Formula (I), E is heterocyclylene; optionally substituted with one or more substituents Q. In certain embodiments, in Formula (I), E is monocyclic heterocyclylene, optionally substituted with one or more substituents Q. In certain embodiments, in Formula (I), E is 3-, 4-, 5-, 6-, or 7-membered heterocyclylene, each optionallysubstituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is 3-membered heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is 4-membered heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is 5-membered heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is 6-membered heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is piperi dindiyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is piperi din- 1,4-diyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is 7-membered heterocyclylene, optionally substituted with one, two, or three substituents Q In certain embodiments, in Formula (I), E is bicyclic heterocyclylene, optionally substituted with one or more substituents Q. In certain embodiments, in Formula (I), E is bridged, fused, or spiro heterocyclylene, each optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is bridged heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is fused heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in Formula (I), E is spiro heterocyclylene, optionally substituted with one, two, or three substituents Q.

[0062] In another embodiment, provided herein is a compound of Formula (II):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mi xture of two or more tautomers, or an i sotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wlierein:R5is hydrogen or R5a; each R5ais independently (i) deuterium, cyano, halo, or nitro; (ii) C1-6 alkyl, Ci-6 heteroalkyl, C2-6 alkenyl, Ci-6 alkynyl, C3-10 cycloalkyl, Ce-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or (iii) -C(O)Rla,-C(O)ORla, --C(O)NRlbR!c, -C(O)SRla, -C(NRla)NRlbRlc, -C(S)Rla, -C(S)ORla, -C(S)NRlbRlc, -0Rla, -OC(O)Rla, -OC(O)ORla, -OC(O)NRlbRlc, -OC(O)SRla, -OC(NRla)NRlbRlc, -OC(S)Rla, -OC(S)ORla, -OC(S)NRlbRlc, -OS(O)Rla, -OS(O)2Rla, -OS(O)NRibRlc, -OS(O)2NRibRlc, -NRlbRlc, ~NRlaC(O)Rld, ~NRlaC(O)ORld, -NRlaC(O)NRlbRlc, -NRlaC(O)SRld, -NRlaC(NRld)NRlbRlc, -NRlaC(S)Rld, -NRlaC(S)ORld, -NRlaC(S)NRlbRlc, -NRlaS(O)Rld, -NR!aS(O)2Rld, -NRlaS(O)NRibRlc, -NRlaS(O)2NRibRlc,SR!a, -S(O)Rla, -S(O)2Rla, -S(O)NRlbRlc, or -S(O)2NRlbRlc; a is an integer of 0, 1, 2, or 3; andR1, R2, R3, R4, Rla, Rlb, Rlc, Rld, RE, A, L, and X are each as defined herein.

[0063] In certain embodiments, in Formula (I) or (II), REis not l,3-dioxo-2-(2,6- dioxopiperidin-3-yl)isoindolinyl, unsubstituted or substituted. In certain embodiments, in Formula (I) or (II), REis not any one of l,3-dioxo-2-(2,6-dioxopiperidin-3-yl)isoindolinyl, 1,3- dioxo-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindolinyl, and 2-(2,6-dioxopiperidin-3-yl)-l- oxoisoindolinyl. In certain embodiments, in Formula (I) or (II), REis not any one of 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)isoindolin-4-yl, l,3-dioxo-2-(2,6-dioxopiperidin-3-yl)isoindolin-5-yl, l,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindolin-4-yl, l,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindolin-5-yl, 2-(2,6-dioxopiperidin-3-yl)-l-oxoisoindolin-4-yl, and 2-(2,6- di oxopiperi di n-3 -yl)- 1 -oxoisoindol in-5 -y 1.

[0064] In yet another embodiment, provided herein is a compound of Formula (III):or an enantiomer, a mixture of enanti omers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein: each R6is independently (i) deuterium, cyano, halo, or nitro; (ii) C1-6 alkyl, Ci-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or (iii) C(O)Rla, -C(O)ORla, -C(O)NRlbRlc, -C(O)SRla, -C(NRla)NRlbRlc, -C(S)Rla, -C(S)ORla,-C(S)NRlbRlc, -0Rla, -OC(O)Rla, -OC(O)ORla, -OC(O)NRlbRlc, -OC(O)SRla, OC(NRla)NRlbRlc, -OC(S)Rla, -OC(S)ORla, -OC(S)NRlbRlc, -OS(O)Rla, -OS(O)2Rla, -OS(O)NRlbRlc, -OS(O)2NRlbRlc, -NRlbRlc, -NRlaC(O)Rld, -NRlaC(O)ORld, -NRlaC(O)NRlbRlc, -NRiaC(O)SRld, ~NRlaC(NRld)NRlbRlc, ~NRlaC(S)Rld, ~NRlaC(S)ORid, -NRlaC(S)NRlbRlc, -NRlaS(O)Rld, -NRlaS(O)2Rld, -NRlaS(O)NRlbRlc, -NRlaS(O)2NRlbRlc, -SRla, -S(O)Rla, -S(O)2Rla, -S(O)NRlbRlc, or -S(O)2NRlbRlc; b is an integer of 0, 1, 2, 3, or 4; andR1, R2, R3, R4, Rla, Rlb, Rlc, Rld, RE, A, L, and X are each as defined herein.

[0065] In certain embodiments, in any one of the formulae provided herein, REis not 1,3- dioxo-2-(2,6-dioxopiperidin-3-yl)isoindolinyl, unsubstituted or substituted. In certain embodiments, in any one of the formulae provided herein, REis not any one of l,3-dioxo-2-(2,6- dioxopiperidin-3-yl)isoindolinyl, l,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindolinyl, and 2-(2,6-dioxopiperidin-3-yl)-l-oxoisoindolinyl. In certain embodiments, in any one of the formulae provided herein, REis not any one of l,3-dioxo-2-(2,6-dioxopiperidin-3-yl)isoindolin-4-yl, l,3-dioxo-2-(2,6-dioxopiperidin-3-yl)isoindolin-5-yl, l,3-dioxo-2-(2,6-dioxopiperidin-3- yI)-6-fluoroisoindolin-4-yl, l,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindolin-5-yl, 2- (2,6-dioxopiperidin-3-yl)-l-oxoisoindolin-4-yl, and 2-(2,6-dioxopiperidin-3-yl)-l-oxoisoindolin-5-yl.

[0066] In yet another embodiment, provided herein is a compound of Formula (I A):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R1, R4, R5a, RE, A, L, Y, and a are each as defined herein.

[0067] In yet another embodiment, provided herein is a compound of Formula (IB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, RJ, R4, R5a, RE, A, L, Y, and a are each as defined herein.

[0068] In yet another embodiment, provided herein is a compound of Formula (IC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R6, RE, A, L, and b are each as defined herein.

[0069] In yet another embodiment, provided herein is a compound of Formula (ID):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R’, R4, R6, RE, A, L, and b are each as defined herein.

[0070] In certain embodiments, in any one of the formulae provided herein, A is a bond. In certain embodiments, in any one of the formulae provided herein, A is heterocyclylene, optionally substituted with one or more substituents Q. In certain embodiments, in any one of the formulae provided herein, A is monocyclic heterocyclylene, optionally substituted with one,two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, A is 3-, 4-, 5-, 6-, or 7-membered heterocyclylene, each optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, A is 3-membered heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, A is 4- membered heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formul ae provided herein, A is 5-membered heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, A is 6-membered heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, A is piperidindiyl or piperazindiyl, each optionally substituted with one, two, or three substituents Q In certain embodiments, in any one of the formulae provided herein, A is piperidin- 1 ,4-diyl or piperazin- 1,4-diyl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, A is 7-membered heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, A is bicyclic heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, A is bridged, fused, or spiro heterocyclylene, each optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, A is bridged heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, A is fused heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, A is spiro heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, A is 3,8-diazabicyclo[3.2.1]octandiyl, octahydropyrrolo[3,4-c]pyrroldiyl, or 2,7-diazaspiro[3.5]nonandiyl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, A is 3,8-diazabicyclo[3.2.1]octan-3,8-diyl, octahydropyrrolo[3,4-c]pyrrol-2,5- diyl, or 2,7-diaza-spiro[3.5]nonan-2,7-diyl. In certain embodiments, in any one of the formulae provided herein, A is -SfOr)-.

[0071] In yet another embodiment, provided herein is a compound of Formula (IIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, RJ, R4, R3a, RE, L, Y, and a are each as defined herein.

[0072] In yet another embodiment, provided herein is a compound of Formula (IIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE, L, Y, and a are each as defined herein.

[0073] In yet another embodiment, provided herein is a compound of Formula (IIC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R’, R4, R6, RE, L, and b are each as defined herein.

[0074] In yet another embodiment, provided herein is a compound of Formula (IID):or an enantiomer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, RJ, R4, Rb, RE, L, and b are each as defined herein.

[0075] In yet another embodiment, provided herein is a compound of Formula (IIIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein: each R7is independently (i) deuterium, cyano, halo, nitro, or oxo; (ii) C1-6 alkyl, Ci-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) -C(O)Rla, -C(O)ORla, -C(O)NRibRlc, -C(O)SRia, -C(NRia)NRlbRlc, -C(S)Rla, -C(S)ORla, -C(S)NRlbRic, ~ORla, -OC(O)Rla, -OC(O)ORla, -OC(O)NRlbRlc, -OC(O)SRla, -OC(NRla)NRlbRlc, -OC(S)Rla, -OC(S)ORla, -OC(S)NRlbRlc, -OS(O)Rla, -OS(O)2Rla, -OS(O)NRlbRlc, -OS(O)2NRlbRlc, -NRlbRlc, -NRlaC(O)Rld, -NRlaC(O)ORld, -NRlaC(O)NRlbRlc, -NRlaC(O)SRld, -NRlaC(NRld)NRlbRlc, -NRlaC(S)Rld, -NRlaC(S)ORld, -NRlaC(S)NRlbRlc, -NRlaS(O)Rld, -NRlaS(O)2Rld, -NR!aS(O)NRlbRlc, -NRlaS(O)2NRlbRlc, -SRla, -S(O)Rla, -S(O)2Rla, -S(O)NRlbRlc, or -S(O)2NRlbRlc; c is an integer of 0, 1, 2, 3, or 4; andR1, R2, R3, R4, Rla, Rlb, Rlc, Rld, R5a, RE, L, Y, and a are each as defined herein.

[0076] In still another embodiment, provided herein is a compound of Formula (IIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R1, R4, R7, R5a, RE, L, Y, a, and c are each as defined herein.

[0077] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC -I):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE2, RE4, XE, YE, m, and n are each as defined herein.

[0078] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-I-a):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE2, RE4, XE, m, and n are each as defined herein.

[0079] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-I-b):(EC-T-b)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, RE4, m, and n are each as defined herein.

[0080] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-I-c):(EC-I-c)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, RE4, m, and n are each as defined herein.

[0081] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-I-d):(EC-I-d)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, RE4, m, and n are each as defined herein.

[0082] In certain embodiments, in any one of the formulae provi ded herein, REis a moiety having the structure of Formula (EC-I-e):(EC-I-e)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or morediastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE2, RE4, m, and n are each as defined herein.

[0083] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-I-f):(EC-I-f)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE2, RE4, m, and n are each as defined herein.

[0084] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-I-g):(EC-I-g)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE2, RE4, m, and n are each as defined herein

[0085] In certain embodiments, in any one of the formulae provi ded herein, REis a moiety having the structure of Formula (EC-I-h):(EC-I-h)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, REJ, RE4, m, and n are each as defined herein.

[0086] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-I-i):(EC-I-i)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, RE3, RE4, m, and n are each as defined herein.

[0087] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-I-j):(EC-I-j)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, REJ, RE4, m, and n are each as defined herein.

[0088] In certain embodiments, in any one of the formulae provi ded herein, REis a moiety having the structure of:or an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein each AEis as defined herein.

[0089] In one embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A1, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A2, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A3, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A4, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A5, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In still another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A6, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

[0090] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure ofor an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

[0091] In one embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A7, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In another embodiment, in a compound ofany one of the formulae provided herein, REis a moiety having the structure of Formula EC-A8, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A9, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A10, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-All, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A12, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A13, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A14, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more di astereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A15, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A16, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in acompound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A17, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A18, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-A19, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In still another embodiment, in a compound of any one of the formulae provided herein, REis a moi ety havi ng the structure of Formula EC-20, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

[0092] In certain embodiments, in any one of the formulae provi ded herein, REis a moiety having the structure of Formula (EC -II):or an enantiomer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE2, RE4, RE5, XE, m, and n are each as defined herein.

[0093] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-II-a):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or morediastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, RE4, RE5, m, and n are each as defined herein.

[0094] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-II-b):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, RE4, RE5, m, and n are each as defined herein.

[0095] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-II-c):(EC-II-c)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, RE4, RE5, m, and n are each as defined herein.

[0096] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-II-d):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE2, RE4, RE5, m, and n are each as defined herein.

[0097] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-II-e):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE2, RE4, RE5, m, and n are each as defined herein.

[0098] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-II-f):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE2, RE4, RE5, m, and n are each as defined herein .

[0099] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of:or an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, oran isotopic variant thereof; wherein each AEis as defined herein.

[0100] In one embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-B1, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-B2, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, R&is a moiety having the structure of Formula EC-B3, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a m oiety having the structure of Formula EC-B4, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

[0101] Ill certain embodiments, in a compound of any one of the formulae provided herein, REis a moiety having the structure of:or an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

[0102] In one embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-B5, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-B6, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof In yet another embodiment, in a compound of any one of the formulae provided herein, R&is a moiety having the structure of Formula EC-B7, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-B8, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-B9, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In still another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-B10, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopi c vari ant thereof.

[0103] In certain embodiments, in a compound of any one of the formulae providedherein, REis a moiety having the structure of:or an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

[0104] In one embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-B11, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC- 812, or an enantiomer, a mixture of enanti omers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-B13, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any oneof the formulae provided herein, REis a moiety having the structure of Formula EC-B14, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-B15, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In still another embodiment, in a compound of any one of the formulae provided herein, Rhis a moiety having the structure of Formula EC-B16, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

[0105] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC -III):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, Z, Z1, Z2, Z3, Z4, and m are each as defined herein.

[0106] In certain embodiments, in any one of the formulae provided herein, one of Z1, Z2, Z3, and Z4is -C= and the remaining three of Z1, Z2, Z3, and Z4are each independently -C(RE4a)=, wherein RE4ais as defined herein. In certain embodiments, in any one of the formulae provided herein, Z1is -C=; and Z2, Z3, and Z4are each independently -C(RE4a)= w'herein RE4ais as defined herein. In certain embodiments, in any one of the formulae provided herein, Z1, Z3, and Z4are each independently ~C(RE4a)=, wherein RE4ais as defined herein; and In certain embodiments, in any one of the formulae provided herein, Z1, Z2, and Z4are each independently -C(RE4a)=, wherein RE4ais as defined herein; and Z3is ~C=. In certain embodiments, in any one of the formulae provided herein, Z1, Z2, and Z3are each independently -C(RE4a)=, wherein RE4ais as defined herein; and Z4is -C=.

[0107] In certain embodiments, in any one of the formulae provided herein, Z!is a bond; one of Z2, Z3, and Z4is -C=, and the remaining two of Z2, Z3, and Z4are each independently -C(RE4a)= or S . wherein RE4ais as defined herein. In certain embodiments, in any one of the formulae provided herein, Z1is a bond; Z2is -C=; Z3is -C(RE4a)=, wherein RE4ais as defined herein; and Z4is -S-. In certain embodiments, in any one of the formulae provided herein, Z1is a bond; Z2is -C=; Z3is -S-; and Z4is -C(RE4a)=, wherein RE4ais as defined herein. In certain embodiments, in any one of the formulae provided herein, Z1is a bond; Z2is -C(RE4a)=, wherein RE4ais as defined herein; Z3is C=; and Z4is -~S~. In certain embodiments, in any one of the formulae provided herein, Z1is a bond; Z2is -S-; Z2is -C=; and Z4is -C(RE4a)=, wherein RE4ais as defined herein. In certain embodiments, in any one of the formulae provided herein, Z1is a bond; Z2is -C(RE4a)=, wherein RE4ais as defined herein; Z3is -S-; and Z4is -C=. In certain embodiments, in any one of the formulae provided herein, Z1is a bond; Z2is -S-; Z3is -C(RE4a)=, wherein RE4ais as defined herein; and Z4is -C=.

[0108] In certain embodiments, in Formula (EC -III), REis not l,3-dioxo-2-(2,6- dioxopiperidin-3-yl)isoindolinyl, unsubstituted or substituted. In certain embodiments, in Formula (EC-III), REis not any one of 1 ,3-dioxo-2-(2,6-dioxopiperidin-3-yl)isoindolinyl, 1,3- dioxo-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindolinyl, and 2-(2, 6-dioxopiperi din-3 -yl)-l- oxoisoindolinyl. In certain embodiments, in Formula (EC-III), REis not any one of l,3-dioxo-2- (2,6-dioxopiperidin-3-yl)isoindolin-4-yl, l,3-dioxo-2-(2,6-dioxopiperidin-3-yl)isoindolin-5-yl, l,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-6-fluoroisoindolin-4-yl, l,3-dioxo-2-(2,6-dioxopiperidin- 3-yl)-6-fluoroisoindolin-5-yl, 2-(2,6-dioxopiperidin-3-yl)-l-oxoisoindolin-4-yl, and 2-(2,6- di oxopiperi din-3 -yl)- 1 -ox oisoindol in-5 -yl .

[0109] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-III-a):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof;wherein AE, RE1, RE2, RE4, Z, m, and n are each as defined herein.

[0110] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-III-b):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, RE4a, Z, and m are each as defined herein. In certain embodiments, RE4ais fluoro. In certain embodiments, Z is CH2 .

[0111] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-III-c):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, RE4a, Z, and m are each as defined herein. In certain embodiments, RE4ais fluoro. In certain embodiments, Z is -CH2-.[001 12] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-III-d):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, RE4a, Z, and m are each as defined herein. In certain embodiments, RE4aisfluoro. In certain embodiments, Z is -CH2-.

[0113] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-III-e):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein n is an integer of 0 or 1; and AE, RE1, RE2, RE4, Z. and m are each as defined herein.

[0114] In certain embodiments, in any one of the formulae provided herein, REis a m oiety having the structure of Formula (EC-III-f):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, RE4a, Z, and m are each as defined herein.

[0115] In certain embodiments, in any one of the formulae provided herein, R is a moiety having the structure of Formula (EC-III-g):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, RE4a, Z, and m are each as defined herein.

[0116] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-IIl-h):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein n is an integer of 0 or 1; and AE, RE1, RE2, RE4, Z, and m are each as defined herein.

[0117] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-III-i):(EC-III-i)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, RE4a, Z, and m are each as defined herein.

[0118] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-III-j):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, RE4a, Z, and m are each as defined herein.

[0119] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-III-k):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein n is an integer of 0 or 1; and AE, RE1, RE2, RE4, Z, and m are each as defined herein.

[0120] In certain embodiments, in any one of the formulae provided herein, REis a moiety having the structure of Formula (EC-III-1):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, RE4a, Z, and m are each as defined herein.

[0121] In certain embodiments, in any one of the formulae provided herein, REis a m oiety having the structure of Formula (EC-III-m):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein AE, RE1, RE2, RE4a, Z, and m are each as defined herein.

[0122] In certain embodiments, REis a moiety having the structure ofor an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; wherein each AEis as defined herein.

[0123] In one embodiment, in a compound of any one of the formulae provided herein, REis a moi ety havi ng the structure of Formula EC-C1, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-C2, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-C3, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In still another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-C4, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

[0124] In certain embodiments, REis a moiety having the structure ofEC-C13 or an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

[0125] In one embodiment, in a compound of any one of the formulae provided herein, REis a moi ety havi ng the structure of Formula EC-C5, or an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-C6, or an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, R&is a moiety having the structure of Formula EC-C7, or an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-C8, or an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-C9, or anenantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-C10, or an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-C11, or an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof In yet another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-C12, or an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof. In still another embodiment, in a compound of any one of the formulae provided herein, REis a moiety having the structure of Formula EC-C13, or an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

[0126] In one embodiment, provided herein is a compound of Formula (IVA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R’, R4, R3a, RE2, RE4, AE, L, XE, Y, a, m, and n are each as defined herein.

[0127] In another embodiment, provided herein is a compound of Formula (VA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or morediastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a, RE1, RE2, RE4, AE, L, Y, a, m, and n are each as defined herein.

[0128] In yet another embodiment, provided herein is a compound of Formula (VIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE1, RE2, R: 4AEL, Y, a, m, and n are each as defined herein.

[0129] In yet another embodiment, provided herein is a compound of Formula (VIIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R’, R4, R5a, RE2, RE4, AE, L, Y, a, m, and n are each as defined herein.

[0130] In still another embodiment, provided herein is a compound of Formula (VIIIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a, RE2, RE4, AE, L, Y, a, m, and n are each as defined herein.

[0131] In one embodiment, provided herein is a compound of Formula (IXA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE2, RE4, AE, L, XE, Y, a, m, and n are each as defined herein.

[0132] In another embodiment, provided herein is a compound of Formula (XA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE1, RE2, RE4, AE, L, Y, a, m, and n are each as defined herein.

[0133] In yet another embodiment, provided herein is a compound of Formula (XIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, RJ, R4, R5a, RE1, RE2, RE4, AE, L, Y, a, m, and n are each as defined herein.

[0134] In yet another embodiment, provided herein is a compound of Formula (XIIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE2, RE4, AE, L, Y, a, m, and n are each as defined herein.

[0135] In still another embodiment, provided herein is a compound of Formula (XIII A):or an enantiomer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; ora pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R1, R4, R3a, RE2, RE4, AE, L, Y, a, m, and n are each as defined herein.

[0136] In one embodiment, provided herein is a compound of Formula (XIV A):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a, RE2, RE4, RE5, AE, L, XE, Y, a, m, and n are each as defined herein.

[0137] In another embodiment, provided herein is a compound of Formula (XVA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE1, RE2, RE4, RE3, AE, L, Y, a, m, and n are each as defined herein.

[0138] In yet another embodiment, provided herein is a compound of Formula (XVIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4,R5a, RE1, RE2, RE4, RE"3, AE, L, Y, a, m, and n are each as defined herein.

[0139] In yet another embodiment, provided herein is a compound of Formula (XVIIA):or an enanti omer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a, RE2, RE4, RE5, AE, L, Y, a, m, and n are each as defined herein.

[0140] In stil l another embodiment, provided herein is a compound of Formula(XVIII A):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R’, R4, R3a, RE2, RE4, RE5, AE, L, Y, a, m, and n are each as defined herein.

[0141] In one embodiment, provided herein is a compound of Formula (XIXA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; ora pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R1, R4, R3a, RE2, RE4, RE5, AE, L, XE, Y, a, m, and n are each as defined herein.

[0142] In another embodiment, provided herein is a compound of Formula (XXA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a, RE1, RE2, RE4, RE5, AE, L, Y, a, m, and n are each as defined herein.

[0143] In yet another embodiment, provided herein is a compound of Formula (XXIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE1, RE2, RE4, RES, AE, L, Y, a, m, and n are each as defined herein.

[0144] In yet another embodiment, provided herein is a compound of Formula (XXIIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or morediastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a, RE2, RE4, RE5, AE, L, Y, a, m, and n are each as defined herein.

[0145] In still another embodiment, provided herein is a compound of Formula (XXIII A):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a, RE2, RE4, RE5, AE, L, Y, a, m, and n are each as defined herein.

[0146] In one embodiment, provided herein is a compound of Formula (XXIVA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a, RE1, RE2, RE4a, AEL, Y, Z, a, and m are each as defined herein. In certain embodiments, RE4ais fluoro. In certain embodiments, Z is -- CH2-.

[0147] In another embodiment, provided herein is a compound of Formula (XXVA):or an enantiomer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R’, R4,Z, a, and m are each as defined herein. In certain embodiments,RE4ais fluoro. In certain embodiments, Z is -CH2-.

[0148] In yet another embodiment, provided herein is a compound of Formula (XXVIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R’, R4, R3a, RE1, RE2, RE4a, AE, L, Y, Z, a, and m are each as defined herein. In certain embodiments, RE4ais fluoro. In certain embodiments, Z is -CH2-.

[0149] In still another embodiment, provided herein is a compound of Formula(XXVIIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or morediastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a, RE1, RE2, RE4a, AE, L, Y, Z, a, and m are each as defined herein.

[0150] In one embodiment, provided herein is a compound of Formula (XXVIIIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a, RE1, RE2, RE4a, AE, L, Y, Z, a, and m are each as defined herein. In certain embodiments, RE4ais fluoro. In certain embodiments, Z is CH2

[0151] In another embodiment, provided herein i s a compound of F ormula (XXIXA) :or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R’, R4, R3a, RE1, RE2, RE4a, AE, L, Y, Z, a, and m are each as defined herein. In certain embodiments, RE4ais fluoro. In certain embodiments, Z is -CH2-.

[0152] In yet another embodiment, provided herein is a compound of Formula (XXXA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE1, RE2, RE4a, AE, L, Y, Z, a, and m are each as defined herein. In certain embodiments, RE4ais fluoro. In certain embodiments, Z is -CH2-.

[0153] In still another embodiment, provided herein is a compound of Formula (XXXIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a, RE1, RE2, RE4a, AE, L, Y, Z, a, and m are each as defined herein.

[0154] In one embodiment, provided herein is a compound of Formula (IVB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or morediastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a, RE2, RE4, AE, L, XE, Y, a, m, and n are each as defined herein.

[0155] In another embodiment, provided herein is a compound of Formula (VB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE1, RE2, RE4, AE, L, Y, a, m, and n are each as defined herein.

[0156] In yet another embodiment, provided herein is a compound of Formula (VIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a, RE1, RE2, RE4, AE, L, Y, a, m, and n are each as defined herein.

[0157] In yet another embodiment, provided herein is a compound of Formula (VIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE2, RE4, AE, L, Y, a, m, and n are each as defined herein.

[0158] In still another embodiment, provided herein is a compound of Formula (VIIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE2, RE4, AE, L, Y, a, m, and n are each as defined herein.

[0159] In one embodiment, provided herein is a compound of Formula (IXB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE2, RE4, AE, L, XE, Y, a, m, and n are each as defined herein.

[0160] In another embodiment, provided herein is a compound of Formula (XB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE1, RE2, RE4, AE, L, Y, a, m, and n are each as defined herein.

[0161] In yet another embodiment, provided herein is a compound of Formula (XIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R.’, R4, R3a, RE1, RE2, RE4, AE, L, Y, a, m, and n are each as defined herein.

[0162] In yet another embodiment, provided herein is a compound of Formula (XIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4,L, Y, a, m, and n are each as defined herein.

[0163] In still another embodiment, provided herein is a compound of Formula (XIIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R’, R4, RY RE2, RE4, AE, L, Y, a, m, and n are each as defined herein.

[0164] In one embodiment, provided herein is a compound of Formula (XIVB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wfierein R1, R2, R1, R4, R5a, RE2, RE4, RE5, AE, L, XE, Y, a, m, and n are each as defined herein.

[0165] In another embodiment, provided herein is a compound of Formula (XVB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, herein.

[0166] In yet another embodiment, provided herein is a compound of Formula (XVIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R’, R4, R3a, RE1, RE2, RE4, RE5, AE, L, Y, a, m, and n are each as defined herein.

[0167] In yet another embodiment, provided herein is a compound of Formula (XVIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE2, RE4, RE3, AE, L, Y, a, m, and n are each as defined herein.

[0168] In still another embodiment, provided herein is a compound of Formula (XVIIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4,ya, m, and n are each as defined herein.

[0169] In one embodiment, provided herein is a compound of Formula (XIXB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R’, R4, RY RE2, RE4, RE5, AE, L, XE, Y, a, m, and n are each as defined herein.

[0170] In another embodiment, provided herein is a compound of Formula (XXB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mi xture of two or more tautomers, or an i sotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a, RE1, RE2, RE4, RE5, AE, L, Y, a, m, and n are each as defined herein.

[0171] In yet another embodiment, provided herein is a compound of Formula (XXIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R.3, R4, herein.

[0172] In yet another embodiment, provided herein is a compound of Formula (XXIIB):or an enanti omer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a, RE2, RE4, RE5, AE, L, Y, a, m, and n are each as defined herein.

[0173] In still another embodiment, provided herein is a compound of Formula (XX1IIB):or an enanti omer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R.’, R4, R3a, RE2, RE4, RE5, AE, L, Y, a, m, and n are each as defined herein.

[0174] In one embodiment, provided herein is a compound of Formula (XXIVB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R’, R4, R3a, RE1, RE2, RE4a, AE, L, Y, Z, a, and m are each as defined herein. In certain embodiments, RE4ais fluoro. In certain embodiments, Z is -CH2-.

[0175] In another embodiment, provided herein is a compound of Formula (XXVB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE1, RE2, RE4a, AE, L, Y, Z, a, and m are each as defined herein. In certain embodiments, RE4ais fluoro. In certain embodiments, Z is -Chh

[0176] in yet another embodiment, provided herein is a compound of Formula (XXVIB):or an enantiomer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; ora pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R1, R4, R5a, RE1, RE2, RE4a, AE, L, Y, Z, a, and m are each as defined herein. In certain embodiments,RE4ais fluoro. In certain embodiments, Z is -CH2-.

[0177] In still another embodiment, provided herein is a compound of Formula(XXVIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE1, RE2, RE4a, AE, L, Y, Z, a, and m are each as defined herein.

[0178] In one embodiment, provi ded herein is a compound of Formula (XXVIIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4,y 2, a, and m are each as defined herein. In certain embodiments, RE4ais fluoro. In certain embodiments, Z is -CH?-.

[0179] In another embodiment, provided herein is a compound of Formula (XXIXB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a, RE1, RE2, RE4a, AE, L, Y, Z, a, and m are each as defined herein. In certain embodiments, RE4ais fluoro. In certain embodiments, Z is -CH2-.

[0180] In yet another embodiment, provided herein is a compound of Formula (XXXB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R3a,£ Y, Z, a, and m are each as defined herein. In certain embodiments,RE4ais fluoro. In certain embodiments, Z is -CH2-.

[0181] In still another embodiment, provided herein is a compound of Formula (XXXIB):or an enantiomer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, R5a, RE1, RE2, RE4a, AE, L, Y, Z, a, and m are each as defined herein.

[0182] In one embodiment, provided herein is a compound of Formula (IIIC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, RE2, RE4, AE, L, XE, m, and n are each as defined herein.

[0183] In another embodiment, provided herein is a compound of Formula (IVC):or an enantiomer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, RJ, R4,RE!, RE2, RE4, AE, L, m, and n are each as defined herein.

[0184] In yet another embodiment, provided herein is a compound of Formula (VC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, RE1, RE2, RE4, AE, L, m, and n are each as defined herein.

[0185] In yet another embodiment, provided herein is a compound of Formula (VIC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R’, R4, RE2, RE4, AE, L, m, and n are each as defined herein.

[0186] In still another embodiment, provided herein is a compound of Formula (VIIC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or morediastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, RE2, RE4, AE, L, m, and n are each as defined herein.

[0187] In one embodiment, provided herein is a compound of Formula (VIIIC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R1, R4, RE2, RE4, RE3, AE, L, XE, m, and n are each as defined herein.

[0188] In another embodiment, provided herein is a compound of Formula (IXC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R’, R4, RE!, RE2, RE4, RE5, AE, L, m, and n are each as defined herein.

[0189] In yet another embodiment, provided herein is a compound of Formula (XC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; ora pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R1, R4, RE1, RE2, RE4, RE5, AE, L, m, and n are each as defined herein.

[0190] In yet another embodiment, provided herein is a compound of Formula (XIC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R1, R4, RE2, RE4, RE3, AE, L, m, and n are each as defined herein.

[0191] In still another embodiment, provided herein is a compound of Formula (XIIC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, RE2, RE4, RE5, AE, L, m, and n are each as defined herein.

[0192] In one embodiment, provided herein is a compound of Formula (XIIIC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or morediastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, RE1, RE2, RE4a, AE, L, Z, and m are each as defined herein. In certain embodiments, RE4ais fluoro. In certain embodiments, Z is -CH?.-.

[0193] In another embodiment, provided herein is a compound of Formula (XIVC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R1, R4, RE!, RE2, RE4a, AE, L, Z, and m are each as defined herein. In certain embodiments, RE4ais fluoro. In certain embodiments, Z is -CII2-.

[0194] In yet another embodiment, provided herein is a compound of Formula (XVC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, RE1, RE2, RE4a, AE, L, Z, and m are each as defined herein. In certain embodiments, RE4ais fluoro. In certain embodiments, Z is -CH2-.

[0195] In still another embodiment, provided herein is a compound of Formula (XVIC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein R1, R2, R3, R4, RE1, RE2, RE4a, AE, L, Z, and m are each as defined herein.

[0196] In certain embodiments, in any one of the formulae provided herein, Rlis Ci-6 alkyl, C3-10 cycloalkyl, or heterocyclyl, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is Ci -6 alkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is methyl, ethyl, propyl, butyl, or pentyl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is ethyl, isopropyl, or pent-3-yl.

[0197] In certain embodiments, in any one of the formulae provided herein, R1is C3-10 cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is monocyclic C3-10 cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is monocyclic C3-10 cycloalkyl, optionally substituted with one, two, or three substituents Q, each of which is independently (i) halo or hydroxyl; or (ii) C1-6 alkyl, optionally substituted with one, two, or three substituents Q.

[0198] In certain embodiments, in any one of the formulae provided herein, R1is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl, each optionally substituted with one, two, or three substituents Q, each of which is independently (i)halo or hydroxyl; or (ii) C1-6 alkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is cyclopentyl, cyclohexyl, or cycloheptyl, each optionally substituted with one, two, or three substituents Q, each of which is independently fluoro, methyl, ethyl, or hydroxyl. In certain embodiments, in any one of the formulae provided herein, R1is cyclopropyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is cyclobutyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is cyclopentyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is cyclopentyl, optionally substituted with one, two, or three substituents Q, each of which is independently (i) halo or hydroxyl; or (ii) C1-6 alkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is cyclopentyl, optionally substituted with one, two, or three substituents Q, each of which is independently fluoro, methyl, ethyl, or hydroxyl. In certain embodiments, in any one of the formulae provided herein, R1is cyclopentyl. In certain embodiments, in any one of the formulae provided herein, R1is cyclohexyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is cycloheptyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is bicyclic C4-10 cycloalkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is bridged, fused, or spiro C4-10 cycloalkyl, each optionally substituted with one, two, or three substituents Q.

[0199] In certain embodiments, in any one of the formulae provided herein, Rlis heterocyclyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is monocyclic heterocyclyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is 3-, 4-, 5-, 6-, or 7-membered heterocyclyl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is 5-membered heterocyclyl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is tetrahydrofuryl, optionally substituted with one, two, or three substituents Q. Incertain embodiments, in any one of the formulae provided herein, R1is 6-membered heterocyclyl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is 7-membered heterocyclyl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is bicyclic heterocyclyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R1is bridged, fused, or spiro heterocyclyl, each optionally substituted with one, two, or three substituents Q.

[0200] In certain embodiments, in any one of the formulae provided herein, R1is ethyl, isopropyl, pent-3-yl, cyclopentyl, cyclohexyl, cycloheptyl, 2-methylcyclopentyl, 2-hydroxy- cyclopentyl, 3-hydroxycyclopentyl, 2-hydroxy-2-m ethyl cyclopentyl, 2-hydroxy-2-ethyl cyclopentyl, 3-hydroxy-2-methylcyclopentyl, 4-hydroxy-2-methylcyclopentyl, 3 -hydroxy cyclohexyl,4-hydroxycyclohexyl, 3-fluoro-5-hydroxycyclohexyl, 3-hydroxy-2-methylcyclohexyl, 5- hydroxy-2-methylcyclohexyl, 3 -hydroxy cycloheptyl, or 4-hydroxy-4-methyltetrahydrofuran-3- yl. In certain embodiments, in any one of the formulae provided herein, R1is cyclopentyl or 2- hydroxy-2-methylcyclopentyl. In certain embodiments, in any one of the formulae provided herein, R is cyclopentyl or' — . In certain embodiments, in any one of the formulae provided herein, R1is

[0201] In certain embodiments, in any one of the formulae provided herein, R2is (i) hydrogen, cyano, or halo; (ii) C1-6 alkyl, C7-15 aralkyl, or heteroaryl, each optionally substituted with one or more substituents Q, or (iii) -C(O)Rla, -C(O)ORla, -C(O)NRlbRlc, -ORla, or -NRlbRlc, wherein each Rla, Rlb, and Rlcis as defined herein. In certain embodiments, in any one of the formulae provided herein, R2is hydrogen. In certain embodiments, in any one of the formulae provided herein, R2is cyano. In certain embodiments, in any one of the formulae provided herein, R2is halo. In certain embodiments, in any one of the formulae provided herein, R2is fluoro, chloro, bromo, or iodo. In certain embodiments, in any one of the formulae provided herein, R2is C1-6 alkyl, C7-15 aralkyl, or heteroaryl, each optionally substituted with oneor more substituents Q. In certain embodiments, in any one of the formulae provided herein, R2is C1-6 alkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R2is methyl, ethyl, isopropyl, cyanomethyl, difluoromethyl, 2,2-difluoroethyl, trifluoromethyl, hydroxycarbonylmethyl, hydroxycarbonyldifluoromethyl, aminocarbonylmethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl, ethoxymethyl, or 2-methoxy ethyl. In certain embodiments, in any one of the formulae provided herein, R2isaralkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R2is benzyl. In certain embodiments, in any one of the formulae provided herein, R2is heteroaryl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R2is oxazol-5-yl.

[0202] In certain embodiments, in any one of the formulae provided herein, R2is -C(O)Rla, -C(O)ORla, -C(O)NRlbRlc, -ORla, or -NRlbRlc, wherein each Rla, Rlb, and Rlcis as defined herein. In certain embodiments, in any one of the formulae provided herein, R2is -C(O)Rla, wherein Rlais as defined herein. In certain embodiments, in any one of the formulae provided herein, R2is C(O)Rla, wherein Rlais C1-6 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of the formulae provided herein, R2is acetyl. In certain embodiments, in any one of the formulae provided herein, R2is C(O)OR!a, wherein Rlais as defined herein. In certain embodiments, in any one of the formulae provided herein, R2is C(O)ORla, wherein Rlais hydrogen or C1-6 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of the formulae provided herein, R2is hydroxycarbonyl or ethoxy carbonyl. In certain embodiments, in any one of the formulae provided herein, R2is -C(O)NRlbRlc, wherein Rlband Ricare each as defined herein. In certain embodiments, in any one of the formulae provided herein, R2is -C(O)NRlbRic, wherein Rlband Rlcare each independently hydrogen or C1-6 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of the formulae provided herein, R2is methylaminocarbonyl or dimethylaminocarbonyl. In certain embodiments, in any one of the formulae provided herein, R2is -ORla, wherein Rlais as defined herein. In certain embodiments, in any one of the formulae provided herein, R2is -ORla, wherein Rlais C1-6 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of the formulae provided herein, R2is 2-ethoxy ethoxy. In certain embodiments, in any one of theformulae provided herein, R2is -NRlbRlc, wherein Rlband Rlcare each as defined herein. In certain embodiments, in any one of the formulae provided herein, R2is -NRlbRlc, wherein Rlband Rlcare each independently hydrogen or Ci-e alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of the formulae provided herein, R2is amino.

[0203] In certain embodiments, in any one of the formulae provided herein, R2is hydrogen, cyano, fluoro, chloro, bromo, iodo, methyl, ethyl, isopropyl, cyanomethyl, difluoromethyl, 2,2-difluoroethyl, trifluoromethyl, hydroxycarbonylmethyl, hydroxycarbonyldifluoro- methyl, aminocarbonylmethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl, ethoxymethyl, 2-methoxyethyl, benzyl, oxazol-5-yl, acetyl, hydroxycarbonyl, ethoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, 2-ethoxyethoxy, or amino. In certain embodiments, in any one of the formulae provided herein, R2is difluoromethyl, acetyl, or dimethylaminocarbonyl. In certain embodiments, in any one of the formulae provided herein, R2is difluoromethyl. In certain embodiments, in any one of the formul ae provided herein, R2is acetyl . In certain embodiments, in any one of the formulae provided herein, R2is dimethylaminocarbonyl.

[0204] In certain embodiments, in any one of the formulae provided herein, R3is hydrogen, deuterium, or C1-6 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of the formulae provided herein, R3is hydrogen. In certain embodiments, in any one of the formulae provided herein, R3is deuterium. In certain embodiments, in any one of the formulae provided herein, R3is C1-6 alkyl, optionally substituted with one, two, or three substituents Q In certain embodiments, in any one of the formulae provided herein, R3is methyl. In certain embodiments, in any one of the formulae provided herein, R3is hydrogen or methyl.

[0205] In certain embodiments, in any one of the formulae provided herein, R4is hydrogen.

[0206] In certain embodiments, in any one of the formulae provided herein, R5is hydrogen, deuterium, halo, or C1-6 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of the formulae provided herein, R5is hydrogen. In certain embodiments, in any one of the formulae provided herein, R5is deuterium. In certain embodiments, in any one of the formulae provided herein, R5is halo. In certain embodiments, inany one of the formulae provided herein, R5is fluoro or chloro. In certain embodiments, in any one of the formulae provided herein, R5is C1-6 alkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R5is methyl or ethyl. In certain embodiments, in any one of the formulae provided herein, R5is hydrogen, fluoro, chloro, methyl, or ethyl. In certain embodiments, in any one of the formulae provided herein, R5is hydrogen. In certain embodiments, in any one of the formulae provided herein, R5is methyl.

[0207] In certain embodiments, in any one of the formulae provided herein, R5ais deuterium, halo, or C1-6 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of the formulae provided herein, R5ais deuterium. In certain embodiments, in any one of the formulae provided herein, R5ais halo. In certain embodiments, in any one of the formulae provided herein, R5ais fluoro or chloro. In certain embodiments, in any one of the formulae provided herein, R3ais C1-6 alkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, R5ais methyl or ethyl In certain embodiments, in any one of the formulae provided herein, R5ais fluoro, chloro, methyl, or ethyl. In certain embodiments, in any one of the formulae provided herein, R5ais methyl.

[0208] In certain embodiments, in any one of the formulae provided herein, RE1is hydrogen, deuterium, halo, or C1-6 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of the formulae provided herein, RE1is hydrogen. In certain embodiments, in any one of the formulae provided herein, RE1is deuterium. In certain embodiments, in any one of the formulae provided herein, RE1is halo. In certain embodiments, in any one of the formulae provided herein, RE1is fluoro. In certain embodiments, in any one of the formulae provided herein, RE1is Ci-e alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of the formulae provided herein, RE1is methyl. In certain embodiments, in any one of the formulae provided herein, REiis hydrogen, deuterium, fluoro, or methyl.

[0209] In certain embodiments, in any one of the formulae provided herein, RE2is hydrogen or C1-6 alkyl, optionally substituted with one or more substituents Q. In certainembodiments, in any one of the formulae provided herein, RE2is hydrogen. In certain embodiments, in any one of the formulae provided herein, RE2is C1-6 alkyl, optionally substituted with one, two, or three substituents Q.

[0210] In certain embodiments, in any one of the formulae provided herein, RE3is hydrogen or Ci-s alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of the formulae provided herein, RE3is hydrogen. In certain embodiments, in any one of the formulae provided herein, RE3is C1-6 alkyl, optionally substituted with one, two, or three substituents Q.

[0211] In certain embodiments, in any one of the formulae provided herein, each RE4is independently deuterium, halo, or C1-6 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of the formulae provided herein, RE4is deuterium. In certain embodiments, in any one of the formulae provided herein, RE4is halo. In certain embodiments, in any one of the formulae provided herein, each RE4is independently fluoro or chloro. In certain embodiments, in any one of the formulae provided herein, RE4is chloro. In certain embodiments, in any one of the formulae provided herein, each RE4is independently Ci-6 alkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, each RE4is independently methyl, ethyl, propyl, each optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, each RE4is independently methyl, isopropyl, or trifluoromethyl. In certain embodiments, in any one of the formulae provided herein, each RE4is independently fluoro, chloro, methyl, isopropyl, or trifluoromethyl. In certain embodiments, in any one of the formulae provided herein, each RE4is independently methyl or trifluoromethyl.

[0212] In certain embodiments, in any one of the formulae provided herein, RE4sis hydrogen, deuterium, or halo. In certain embodiments, in any one of the formulae provided herein, RE4sis hydrogen. In certain embodiments, in any one of the formulae provided herein, RE4Sis deuterium. In certain embodiments, in any one of the formulae provided herein, RE4sis halo. In certain embodiments, in any one of the formulae provided herein, RE:4Sis fluoro or chloro. In certain embodiments, in any one of the formulae provided herein, RE4sis fluoro. In certain embodiments, in any one of the formul ae provided herein, RE4sis hydrogen, deuterium,fluoro, or chloro.

[0213] In certain embodiments, in any one of the formulae provided herein, REsis hydrogen or C1-6 alkyl, optionally substituted with one or more substituents Q. In certain embodiments, in any one of the formulae provided herein, RE5is hydrogen. In certain embodiments, in any one of the formulae provided herein, RE5is C1-6 alkyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, RE5is methyl.

[0214] In certain embodiments, in any one of the formulae provided herein, AEis (i) a bond; or (ii) C2-6 alkynylene, heterocyclylene, C1-6 heteroalkylene-Ce-u arylene, Ci-6 heteroalkyl ene-heterocycly I ene, or C2-6 alkynylene-heterocyclylene, each optionally substituted with one or more substituents Q. In certain embodiments, in any one of the formulae provided herein, AEis a bond. In certain embodiments, in any one of the formulae provided herein, AEis C2-6 alkynylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, AEis ethynediyl. In certain embodiments, in any one of the formulae provided herein, AEis heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, AEis monocyclic heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, A&is 3-, 4-, 5-, 6-, or 7-membered heterocyclylene, each optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, AEis 5- or 6-membered heterocyclylene, each optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, AEis 6-membered heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, AEis piperidindiyl or piperazindiyl, each optionally substituted with one, two, or three substituents Q In certain embodiments, in any one of the formulae provided herein, AEis piperidin-l,3-diyl, piperidin- 1 ,4- diyl, or piperaz-l,4-diyl.

[0215] In certain embodiments, in any one of the formulae provided herein, AEis C1-6 heteroalkylene-Ce-14 arylene, optionally substituted with one, two, or three substituents Q. Incertain embodiments, in any one of the formulae provided herein, AEis C1-6 heteroal kylene- phendiyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, AEis (phendiyl)oxymethanediyl. In certain embodiments, in any one of the formulae provided herein, AEis C1-6 heteroalkylene- heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, AEis C1-6 heteroalkylene-(monocyclic heterocyclylene), optionally / substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, AEis C1-6 heteroal kylene-(3-, 4-, 5-, 6-, or 7-membered heterocyclylene), each optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, AEis Ci-6 heteroalkylene-(6-membered heterocyclylene), optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, AEis Ci-6 heteroalkylene-piperazindiyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, AEis C1-6 heteroal kylene- piperazin- 1,4-diyl, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein,

[0216] In certain embodiments, in any one of the formulae provided herein, AEis C2.6 alkynylene-heterocyclylene, optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, AEis C2-6 alkynylene- (monocyclic heterocyclylene), optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, AEis C2-6 alkynylene-(3-, 4-, 5-, 6-, or 7-membered heterocyclylene), each optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, AEis C2-6 alkynylene-(6-membered heterocyclylene), optionally substituted with one, two, or three substituents Q. In certain embodiments, in any one of the formulae provided herein, AEis (piperidindiyl)-ethynediyl. In certain embodiments, in any one of the formulae provided herein,AEis a bond, piperi din- 1,3 -diyl, piperidin-1 ,4-diyl, piperaz-l,4-diyl, (phen-1,4- diyl)oxymethanediyl, ( pi peridin- 1 ,4-diy l)ethynediy

[0217] In certain embodiments, in any one of the formulae provided herein, L is a linker having the structure of ZL(RL-ZL)z-, wherein: each RLis independently C1-10 alkylene, C2-10 alkenylene, C2-10 alkynylene, C3-10 cycloalkylene, Ce-i4 arylene, heteroarylene, or heterocyclylene, each of which is optionally- substituted with one or more, in one embodiment, one, two, three, or four, substituents Q; each ZLis independently a bond, -C(O)-, -C(O)O- -C(O)NRlb-, -C(O)S- -C(NRla)NRlb-, -C(S)-, -C(S)O-, -C(S)NRlb-, -O-, -OC(O)O-, -OC(O)NRlb-, -OC(O)S-, -OC(NRla)NRlb- -OC(S)O- -OC(S)NRlb-, -OS(O)-, -OS(O)2-, -OS(O)NRlb- -OS(O)2NRlb-, -NRlb-, -NRlaC(O)NRlb-, -NRlaC(O)S-, -NRlaC(NRld)NRlb-, -NRlaC(S)NRlb-, -NRlaS(O)NRlb-, -NRlaS(O)2NR!b- -S-, -S(O)-, -S(O)2-, -S(O)NRlb-, or -S(O)2NRlb--; where each Rla, Rlb, and Rldis as defined herein; and z is an integer of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0218] In certain embodiments, each RLis independently Ci-io alkylene, C2-10 alkynylene, C3-10 cycloalkylene, Ce-14 arylene, heteroarylene, or heterocyclylene, each optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q; each ZLis independently a bond, -C(O)-, -C(O)NRlb- -C(NRla)NRlb-, -O-, -OC(O)NRlb-, -NRlb- -NRlaC(O)NRlb-, -NRlaC(NRld)NRib---, -NRlaS(O)NRlb-, -NRlaS(O)2NRlb-, -S-, -S(O)-,-S(O)2-, -S(O)NRIb-, or -■S(O)2NRlb-; and z is an integer of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; where each Rla, Rlb, and Rldis as defined herein.

[0219] In certain embodiments, each RLis independently Ci-io alkylene, C2-io alkynylene, C3-10 cycloalkylene, Ce-14 arylene, heteroarylene, or heterocyclylene, each optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q; each ZLis independently a bond, -C(O)-, -C(O)NRlb-, -O-, -OC(O)NRlb-, -NRlb-, -NRlaC(O)NRlb- or -NRlaC(NRld)NRlb--; and z is an integer of 1, 2, 3, 4, 5, 6, 7, or 8; where each Rla, Rlb, and Rldis as defined herein.

[0220] In certain embodiments, each RLis independently methanediyl, ethanediyl, propanediyl, butanediyl, pentanediyl, hexanediyl, heptanediyl, octanediyl, nonanediyl, decanediyl, ethynediyl, cyclobutanediyl, cyclopentanediyl, cyclohexanediyl, cycloheptanediyl, bicyclo[2.2.2]octanediyl, phendiyl, pyrazoldiyl, imidazoldiyl, tetrazoldiyl, pyrimidindiyl,5.6.7.8.9.10-hexahydrocycloocta[< / ]-pyridazindiyl, 1,3-dioxandiyl, piperazindiyl, piperidindiyl, or 3,9-diazaspiro[5.5]undecanediyl, each optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q; each ZLis independently a bond, -C(O)-, -C(O)O-, -C(O)NH-, -OC(O)NH-, -O-, -NH-, -N(CHs)-, or -NHC(O)NH-; and z is an integer of 1, 2, 3, 4, 5, 6, 7, or 8.

[0221] In certain embodiments, each RLis independently methanediyl, ethane- 1,2-diyl, propane-1, 3-diyl, butane- 1,4-diyl, pentane- 1,5-diyl, hexane- 1,6-diyl, heptane-l,7-diyl, octane- 1 ,8-diyl, nonane- 1,9-diyl, decane- 1 ,10-diyl, ethyne- 1,2-diyl, cyclobutane- 1, 3-diyl, cyclopentane- 1, 3-diyl, cyclohexane- 1, 3-diyl, cyclohexane-l,4-diyl, cycloheptane- 1,3 -diyl, cycloheptane- 1,4- diyl, bicyclo[2.2.2]octane- 1,4-diyl, phen-1, 3-diyl, phen- 1,4-diyl, pyrazol- 1,3 -diyl, pyrazol-1,4- diyl, imidazol- 1,4-diyl, l,2,3-triazol-l,4-diyl, pyrimidin-2,4-diyl, pyrimidin-2,5-diyl,5.6.7.8.9.10-hexahydrocycloocta[J]-pyridazin-l ,7-diyl, pyrazolidin- 1,3 -diyl, pyrazolidin- 1,4- diyl, l,3-dioxan-2,5-diyl, piperazin-1, 4-diyl, piperidin-1, 3-diyl, piperidin-l,4-diyl, or 3,9- diazaspiro[5.5]-undecane-3,9-diyl, each optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q; each ZLis independently a bond, --C(O)- -C(O)O-, -C(O)NH- -OC(O)NH-, -O-, -NH-, -N(CH3)-, or -NHC(O)NH-; and z is an integer of 1, 2, 3, 4, 5, 6, 7, or 8.

[0222] In certain embodiments, each RLis independently methanediyl, ethane- 1,2-diyl, propane-1, 3-diyl, cyclohex- 1,3 -diyl, cyclohex- 1,4-diyl, phen- 1,3 -di yl, phen- 1,4-diyl, azetidin- 1 , 3-diyl, piperazin-1, 4-diyl, piperidin-1, 3-diyl, piperi din- 1,4-diyl, morpholin-2, 4-diyl, 4,7- diazaspiro[2.5]octan-4,7-diyl, 3-azabicyclo[3.2.1]octan-3,8-diyl, 8-azabicyclo[3.2.1]octan-3,8- diyl, 3,8-diazabicyclo[3.2.1]octan-3,8-diyl, or 2,7-diazaspiro[3.5]nonan-2,7-diyl, each optionally substituted with one, two, or three substituents, wherein each substituent is independently fluoro or methyl; each ZLis independently a bond or -O-; and z is an integer of 2, 3, 4, or 5.

[0223] In certain embodiments, each RLis independently methanediyl, ethane- 1,2-diyl, l,l-difluoroethane-l,2-diyl, propane-1, 3-diyl, cyclohex-1, 3-diyl, cyclohex- 1 ,4-diyl, phen-1,3- diyl, phen- 1,4-diyl, azetidin-1, 3-diyl, 3-fluoroazetidin-l, 3-diyl, piperazin- 1,4-diyl, 2- methylpiperazin- 1 , 4-diyl, piperidin-1 ,3 -diyl, piperi din- 1 , 4-diyl, 4-fluoropiperi din- 1 , 4-diyl, morpholin-2, 4-diyl, 4,7-diazaspiro[2.5]octan-4,7-diyl, 3-azabicyclo[3.2. l]octan-3,8-diyl, 8- azabicyclo[3.2.1 ]octan-3,8-diyl, 3,8-diazabicyclo[3.2.1]octan-3,8-diyl, or 2,7- diazaspiro[3.5]nonan-2,7-diyl; each ZLis independently a bond or -O-; and z is an integer of 2, 3, 4, or 5.

[0224] In certain embodiments, in any one of the formulae provided herein, L is:wherein each ALis independently a bond, -O-, -NH-, or -N(CH3)-.

[0225] In certain embodiments, in any one of the formulae provided herein, L is:wherein each ALis independently a bond, -0-, -NH-,

[0226] In certain embodiments, in any one of the formulae provided herein, L is:wherein each ALis independently a bond, -0---,or -N(CH3 )---.

[0227] In certain embodiments, in any one of the formulae provi ded herein, L is:wherein each ALis independently a bond, -0-, -NH-, or -N(CH3)-; and wherein each amino(NH) group is optionally substituted with methyl.

[0228] In certain embodiments, in any one of the formulae provided herein, L is:wherein each ALis independently a bond, -O-, -NH-,wherein each amino(NH) group is optionally substituted with methyl.

[0229] In certain embodiments, in any one of the formulae provided herein, L is:wherein each ALis independently a bond, -O-, -NH-, or -N(CH3)-; and wherein each amino group (NH) is optionally substituted with methyl.

[0230] In certain embodiments, in any one of the formulae provided herein, L is:wherein each ALis independently a bond, -0- -NH-, or -N(CHs)-; and wherein each amino(NH) group is optionally substituted with methyl.

[0231] In certain embodiments, in any one of the formulae provi ded herein, L is:wherein each ALis independently a bond, -O-, -NH-, or -N(CH3)-.

[0232] In certain embodiments, L is:wherein each ALis independently a bend, -O-, -NH-, or ~N(CH3)--; and wherein each amino group (NH) is optionally substituted with methyl.

[0233] In certain embodiments, in any one of the formulae provided herein, L is:wherein each ALis independently a bond, -O-, -NH-,wherein each aminogroup (NH) is optionally substituted with methyl.

[0234] In certain embodiments, in any one of the formulae provided herein, L is:wherein each ALis independently a bond, -0-, -NH-, or -N(CH3)-.

[0235] In certain embodiments, in any one of the formulae provided herein, L is:wherein each ALis independently a bend, -O-, -NH- or -N^CTH)-; and wherein each amino group (NH) is optionally substituted with methyl.

[0236] In certain embodiments, in any one of the formulae provided herein, L is:wherein each ALis independently a bond, -O-, -NH-, or -N(CH3)~-; and wherein each amino group is optionally substituted with methyl.

[0237] In certain embodiments, in any one of the formulae provided herein, L is:

[0238] In certain embodiments, in any one of the formulae provided herein, L is:

[0239] In certain embodiments, in any one of the formulae provi ded herein, L is:

[0240] In certain embodiments, in any one of the formulae provided herein, L is:

[0241] In certain embodiments, in any one of the formulae provided herein, L is:

[0242] In certain embodiments, in any one of the formulae provided herein, L is:

[0243] In certain embodiments, in any one of the formulae provided herein, L is:

[0244] In certain embodiments, in any one of the formulae provided herein, L is:

[0245] In certain embodiments, in any one of the formulae provided herein, L is:

[0246] In certain embodiments, in any one of the formulae provided herein, L is:

[0247] In certain embodiments, in any one of the formulae provided herein, L is:- I l l -

[0248] In certain embodiments, in any one of the formulae provided herein, X is a bond.In certain embodiments, in any one of the formulae provided herein, X is -C(O)-.

[0249] In certain embodiments, in any one of the formulae provi ded herein, XEis C(RE1), wherein R&1is as defined herein. In certain embodiments, in any one of the formulae provided herein, XEis C(H). In certain embodiments, in any one of the formulae provided herein, XEis N.

[0250] In certain embodiments, in any one of the formulae provided herein, Y isC(R5)=, wherein R3is as defined herein. In certain embodiments, in any one of the formulaeprovided herein, Y is -C(H)=, In certain embodiments, in any one of the formulae provided herein, Y is -N=.

[0251] In certain embodiments, in any one of the formulae provided herein, YEis a bond. In certain embodiments, in any one of the formulae provi ded herein, YEis -N(RE3)-, wherein REIis as defined herein.

[0252] In certain embodiments, in any one of the formulae provided herein, Z is -CHi-. In certain embodiments, in any one of the formulae provided herein, Z is ~C(O)~.

[0253] In certain embodiments, in any one of the formulae provided herein, a is an integer of 0 or 1. In certain embodiments, in any one of the formulae provided herein, a is an integer of 0. In certain embodiments, in any one of the formulae provided herein, a is an integer of 1.

[0254] In certain embodiments, in any one of the formulae provided herein, m is an integer of 0, 1, or 2. In certain embodiments, in any one of the formulae provided herein, m is an integer of 0. In certain embodim ents, in any one of the formulae provided herein, m is an integer of 1. In certain embodiments, in any one of the formulae provided herein, m is an integer of 2.

[0255] In certain embodiments, in any one of the formulae provided herein, n is an integer of 0, 1, or 2. In certain embodiments, in any one of the formulae provided herein, n is an integer of 0. In certain embodiments, in any one of the formulae provided herein, n is an integer of 1. In certain embodiments, in any one of the formulae provided herein, n is an integer of 2.

[0256] All combinations of the embodiments provided herein for the groups in the formulae described herein are within the scope of this disclosure.

[0257] In one embodiment, provided herein is a compound of: 7-cyclopentyl-2-((4-((2-(4-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperazin-l-yl)ethyl)carbamoyl)phenyl)amino)-Az,A’-dimethyl-7 / / -pyrrolo[2,3-t7]pyiimidine-6- carboxamide A101;7-cyclopentyl-2-((4-((4-(4-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperazin-l-yl)butyl)carbamoyl)phenyl)amino)- / V,iV-dimethyl-7 / f-pyrrolo[2,3-<7]pyrimidine-6-carboxamide Al 02;7-cyclopentyl-2-((4-((6-(4-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperazin-l-yl)hexyl)carbamoyl)phenyl)amino)-Ar,Ar-dimethyl-7H-pyrrolo[2,3-<7]pyrimidine-6- carboxamide A103;7-cyclopentyl-2-((4-(4-(2-(4-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperazin- 1 -yl)ethyl)piperazin- 1 -yl)phenyl)amino)-ApV-dimethyl-7 / / -pyrrolo[2,3 -t / ]pyrimidine- 6-carboxamide A104;7-cyclopentyl-2-((4-(4-(4-(4-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperazin- 1 -yl)butyl)piperazin- 1 -yl)phenyl)amino)-A^V-dimethyl-7 / / -pyrrolo[2,3 -t / ]pyrimidine- 6-carboxamide A105;7-cyclopentyi-2-((4-(4-(2-(l-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperidin-4-yl)ethyl)piperazin-l-yl)phenyl)amino)-A7,A'r-dimethyl-7 / 7-pyrrolo[2,3<(|pyrimidine- 6-carboxamide A106;7-cyclopentyl-2-((4-(4-(4-(l-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperidin-4-yl)butyl)piperazin-l-yl)phenyl)amino)-A,A-dimethyl-77 / -pyrrolo[2,3-<7]pyrimidine- 6-carboxamide A107,7-cyclopentyl-2-((4-(4-(2-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetamido)- ethyl)piperazin-l-yl)phenyl)amino)-Ar,A’-dimethyl-7 / / -pyrrolo[2,3-^pyrimidine-6-carboxamide A108;7-cyclopentyl-2-((4-(4-(2-(2-(3-(2,6-dioxopiperidin-3-yl)-4-methylphenoxy)- acetamido)ethyl)piperazin-l-yl)phenyl)amino)-A;,A'r-dimethyl-7 / / -pyrrolo[2,3-t7]pyrimidine-6- carboxamide A109;7-cyclopentyl-2-((4-(4-(2-(2-(3-(2,6-dioxopiperidin-3-yl)-4-(trifluoromethyl)- phenoxy)acetamido)ethyl)piperazin-l-yl)phenyl)amino)-AAV-dimethyl-7 / f-pyrrolo[2,3-J]- pyrimidine-6-carboxamide A110;7-cyclopentyl-2-((4-(4-(3-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetamido)- propyi)piperazin-l-yl)phenyl)amino)-7V,Az-dimethyl-7J / -pyrrolo[2,3-^pyrimidine-6-carboxamide Alli;7-cyclopentyl-2-((4-(4-(3-(2-(3-(2,6-dioxopiperidin-3-yl)-4-methylphenoxy)- acetamido)propyl)piperazin-l-yl)phenyl)amino)-A'r,A-dimethyl-7H-pyrrolo[2,3-(7]pyrimidine-6- carboxamide Al 12;7-cyclopentyl-2-((4-(4-(3-(2-(3-(2,6-dioxopiperidin-3-yl)-4-(trifluoromethyl)- phenoxy)acetamido)propyl)piperazin-l-yl)phenyl)amino)-A,A-dimethyl-7Ar-pyrrolo[2,3-dr]- pyrimidine-6-carboxamide A113;7-cyclopentyl-2-((4-((2-(4-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperazin-l-yl)ethyI)carbamoyl)phenyl)amino)-A'',Ar-dimethyl-7fir-pyrrolo[2,3-J]pyrimidine-6- carboxamide Al 14;7-cyclopentyl-2-((4-((4-(4-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperazin-l-yl)butyl)carbamoyl)phenyl)amino)-A7,A'r-dimethyl-777-pyrrolo[2,3-tf|pyrimidine-6- carboxamide Al 15; or7-cyclopentyl-2-((4-((6-(4-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperazin-l-yl)hexyl)carbamoyl)phenyl)amino)-Ar,A-dimethyl-7 / Apyrrolo[2,3-rf|pyrimidine-6- carboxamide Al 16; or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0258] In another embodiment, provided herein is a compound of:7-cyclopentyl-2-((4-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- phenyl)amino)-A / / -dimethyl-7 / 7-pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A117, 7-cyclopentyl-2-((4-(4-(4-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yl)- phenyl)amino)-A",A-dimethyl-7 / f-pyrrolo[2,3-J]pyrimidine-6-carboxaniide A118;7-cyclopentyl-2-((4-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l-yl)- phenyl)amino)-7V,A'-dimethyl-7 / f-pyrrolo[2,3-t / ]pyriniidine-6-carboxamide A119;7-cyclopentyl-2-((4-(4-(3-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l-yl)- phenyl)amino)-A",A’-dimethyl-7 / 7-pyrrolo[2,3-J]pyrimidine-6-carboxamide A120;7-cyclopentyl-2-((4-(4-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)ethyl)piperazin-l- yl)phenyl)amino)-A,A7-dimethyl-7Z / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide A121;7-cyclopentyl-2-((4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethyl)phenyl)amino)-A\A’-dimethyl-7 / f-pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A122;7-cyclopentyl-2-((4-(2-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethyl)phenyl)amino)-Az,A;-dimethyl-7 / / -pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A123;7-cyclopentyl-2-((4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethoxy)phenyl)amino)-Az,A-dimethyl-7 / / -pyrrolo[2,3-tZ]pyrimidine-6-carboxamide A124;7-cy cl opentyl-2-((4-(2-(4-(3 -(2, 6-di oxopiperi din-3 -yl )phenyl)pi perazin- 1 -yl)- ethoxy)plienyl)amino)-A,r,A-dimethyl-7 / f-pyrrolo[2,3-< / ]pyriniidiiie-6-carboxamide A125;7-cyclopentyl-2-((4-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)phenyl)amino)-A,Ar-dimethyl-7 / / -pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A126;7-cyclopentyl-2-((4-(4-(l-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)phenyl)amino)-A",A'r-dimethyl-7 / 7-pyrrolo[2,3-^]pyrimidine-6-carboxaniide A127;7-cyclopentyl-2-((4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yI)- ethyl)phenyl)amino)-Ar,Ar-dimethyl-7J7-pyrrolo[2,3-« / ]pyrimidine-6-carboxamide A128;7-cyclopentyl-2-((4-(2-(4-(3-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yl)- ethyl)phenyl)amino)-A,Ar-dimethyl-7H-pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A129;7-cyclopentyl-2-((4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yl)- ethoxy)phenyl)amino)-Az,A-dimethyl-7 / / -pyrrolo[2,3-tZ]pyrimidine-6-carboxamide A130;7-cyclopentyl-2-((4-(2-(4-(3-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yl)- ethoxy)phenyl)amino)-Ay / V-dimethyl-7H-pyrrolo[2,3-^pyrimidine-6-carboxamide A131;7-cyclopentyl-2-((4-((4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)methyl)phenyl)amino)-A^V-dimethyl-7Z7-pyrrolo[2,3-i / ]pyrimidine-6- carboxamide A132;7-cyclopentyl-2-((4-(2-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l -yl)ethoxy)phenyl)amino)-AVV-dimethyl-7 / f-pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A133;7-cyclopentyl-2-((4-(2-(4-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)ethoxy)phenyl)amino)-A,A7-dimethyl-7 / 7-pyrrolo[2,3-^pyrimidine-6-carboxamide A134;7-cyclopentyl-2-((4-(2-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4- yl)piperazin-l-yl)ethyl)phenyl)amino)-A'’,Ar-dimethyl-7 / 7-pyrrolo[2,3-d]pyriniidine-6- carboxamide A135;7-cyclopentyl-2-((4-(2-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l -yl)ethyl)phenyl)amino)-A7,A'r-dimethyl-7H-pyrrolo[2,3-< / |pyrirnidine-6-carboxamide A136;7-cyclopentyl-2-((4-(2-(4-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)ethyl)phenyl)amino)-Ar,Ar-dimethyl-77 / -pyrrolo[2,3-<7]pyrimidine-6-carboxamideA137;7-cyclopentyi-2-((4-(4-(l-(4-(2,6-dioxopiperidin-3-yl)benzyl)piperidin-4- yl)piperazin-l-yl)phenyl)amino)-A,A’-dimethyl-7 / / -pyrrolo[2,3-< / jpyrimidine-6-carboxamide A138;7-cyclopentyl-2-((4-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperidin-4-yl)- piperazin- 1 -yl)phenyl)amino)-A^V-dimethyl-77 / -pyrrolo[2,3 -d]pyrimidine-6-carboxamide A139;7-cyclopentyl-2-((4-(4-(l-(3-(2,6-dioxopiperidin-3-yl)phenethyl)piperidin-4-yl)- piperazin-l-yl)phenyl)amino)-A,A'r-dimethyl-7J7-pyrrolo[2,3-< / |pyrimidine-6-carboxamide Al 40;7-cyclopentyl-2-((4-(4-((l-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- methyl)piperazin-l-yl)phenyl)amino)-Az,7V-dimethyl-7 / / -pyrrolo[2,3-<T]pyrimidine-6- carboxamide A141;7-cyclopentyl-2-((4-(4-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- methyl)piperazin-l-yl)phenyl)amino)-Ap\Mimethyl-7Z / -pyrrolo[2,3-<7]pyrimidine-6- carb oxami de Al 42;7-cyclopentyl-2-((4-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- ethyl)piperazin-l-yl)phenyl)amino)-Ar,Ar"dimetliyl-7 / Apyrrolo[2,3-<7]pyrimidine-6-carboxamide A143;7-cyclopentyl-2-((4-(4-(2-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- ethyl)piperazin-l-yl)phenyl)amino)-ArJA7-dimethyl-7 / 7-pyrrolo[2,3-tZ]pyrimidine-6-carboxamide A144;7-cyclopentyl-2-((5-(4-(3-(4-(4-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yl)- phenyl)piperazin-l-yl)pyridin-2-yl)amino)-AAV-dimethyl-7J7-pyrrolo[2,3-^pyrimidine-6- carboxamide Al 45;7-cyclopentyl-2-((5-(4-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l- yl)phenyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A7-dimethyl-7J / -pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A146;7-cyclopentyl-2-((5-(4-(3-(4-(3-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l- yl)phenyl)piperazin-l-yl)pyridin-2-yl)amino)-A7,A’-dimethyl-777-pyrrolo[2,3-<7]pyrimidine-6- carboxamide A147;7-cyclopentyl-2-((5-(4-(4-(4-(4-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yl)- phenyl)piperazin-l-yl)pyridin-2-yl)amino)-ApV-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide Al 48;7-cyclopentyl-2-((5-(4-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l- yl)phenyl)piperazin-l-yl)pyridin-2-yl)amino)-A,A-dimethyl-777-pyrrolo[2,3-i7]pyrimidine-6- carboxamide A149;7-cyclopentyl-2-((5-(4-(4-(4-(3-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l- yl)phenyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,AMimethyl-7JH-pyrrolo[2,3-J]pyrimidine-6- carboxamide A150;7-cyclopentyl-2-((5-(4-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l -yl)- benzyl)piperazin-l-yl)pyridin-2-yl)amino)-ApV-dimethyi-7 / / -pyrrolo[2,3-fl?]pyrimidine-6- carb oxami de A 151 ;7-cyclopentyi-2-((5-(4-(4-((4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- methyl)phenyl)piperazin-l-yl)pyridin-2-yl)amino)-A’,A'-dimethyl-7Ar-pyiTolo[2,3-<7]pyrimidine- 6-carboxamide A152;7-cyclopentyl-2-((5-(4-(4-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- benzyl)piperazin-l-yl)pyridin-2-yl)amino)-Ap\Mimethyl-7 / / -pyrrolo[2,3-d]pyrimidine-6- carboxamide A153; or7-cyclopentyl-2-((5-(4-(4-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- methyl)phenyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A7-dimethyl-7J / -pyrrolo[2,3-t / ]pyrimidine- 6-carboxamide A154; or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0259] In yet another embodiment, provided herein is a compound of:7-cyclopentyl-2-((5-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)cyclohexyl)- piperazin-l-yl)pyridin-2-yl)amino)-A / ,A''-dimethyl-7Ar-pyrrolo[2,3-47]pyrimidine-6-carboxamide A155;7-cyclopentyl-2-((5-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperidin-4-yl)- piperazin-l-yl)pyridin-2-yl)amino)-A\A-dimethyl-7 / f-pyrrolo[2,3-tf|pyrimidine-6-carboxamide A156;7-cyclopentyl-2-((5-(4-(l-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)ethyl)- piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-AT,ALdimethyl-7 / / -pyrrolo[2,3-< / ]pyrimidine-6- carboxamide A157;7"Cyclopentyl-2-((5-(4-(l-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- methyl)piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-A^V-dimethyl-7 / 7-pyrrolo[2,3-t / ]- pyrimidine-6-carboxamide A158;7-cyclopentyl-2-((5-(4-((r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]- 4-yl)methyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A-dimethyl-7 / / r-pyrrolo[2,3-tZ]-pyrimidine-6- carboxamide A159:7-cyclopentyl-2-((5-(4-(l-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)ethyl)- piperidin-4-yl)piperazin-l -yl)pyridin-2-yl)amino)-A,A'r-dimethyl-7 / 7-pyrrolo[2,3-< / |pyrimidine-6- carboxamide A160;7-cyclopentyl-2-((5-(4-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l- yl)propyl)piperazin-l-yl)pyridin-2-yl)amino)-A’,Ar-dimetliyl-7 / 7-pyrrolo[2,3-d]pyrimidine-6- carboxamide A161;7-cyclopentyl-2-((5-(4-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]-3-yl)piperazin-l-yl)pyridin-2-yl)amino)- / V’,A7-dimethyl-7JH-pyiTolo[2,3-J]pyrimidine-6- carboxamide A162:7-cyclopentyl-2-((5-(4-(l-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4- yl)methyl)piperidin-3-yl)piperazin-l-yl)pyridin-2-yl)amino)-A7,A-dimethyl-777-pyrrolo[2,3-fi(]- pyrimidine-6-carboxamide A163;7-cyclopentyl-2-((5-(4-(l-(((25)-4-(4-(2,6-dioxopiperidin-3-yl)phenyl)- morpholin-2-yl)methyl)piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-A7Ar-dimethyl-7 / 7- pyrrolo[2,3-i / ]pyrimidine-6-carboxamide A164;7-cyclopentyl-2-((5-(4-(l-(((2A)-4-(4-(2,6-dioxopiperidin-3-yl)phenyl)- morpholin-2-yl)methyl)piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-7VjV-dimethyl-7 / / - pyrrolo[2,3-i(lpyrimidine-6-carboxamide A165;7-cyclopentyi-2-((5-(4-(3-(l-(4-(2,6-dioxopiperidin-3-yl)benzyl)piperidin-4-yl)- cyclohexyl)piperazin-l-yl)pyridin-2-yl)amino)-A7,A7-dimethyl-7Z / -pyrrolo[2,3-(7]pyrimidine-6- carboxamide A166;7-cyclopentyl-2-((5-(4-(l-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)azetidin-3-yl)- methyl)piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-A7A7-dimethyl-7 / / -pyrrolo[2,3-<7]- pyrimidine-6-carboxamide A167;7-cyclopentyl-2-((5-(4-(((2S)-4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)morpholin-2-yl)methyl)piperazin-l-yl)pyridin-2-yl)amino)-A7^-dimethyl-7H-pyrrolo[2,3- tZ]pyrimidine-6-carboxamide A168;7-cyclopentyl-2-((5-(4-(((2 / ?)-4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)morpholin-2-yl)methyl)piperazin-l-yl)pyridin-2-yl)amino)-A7,Ar-dimethyl-7 / f-pyrrolo[2,3- <7jpyrimidine-6-carboxamide A169;7-cyclopentyl-2-((5-(4-((4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- cyclohexyl)methyl)piperazin-l-yl)pyridin-2-yl)amino)-A'; / V-dimethyl-7H-pyrrolo[2,3-<7]- pyrimidine-6-carboxamide A170;7-cyclopentyl-2-((5-(4-(2-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l- yl)cyclohexyl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-A',,A?-dimethyl-77f-pyrrolo[2,3-c7]- pyrimidine-6-carboxamide A171;7-cyclopentyl-2-((5-(4-(l-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l- yl)ethyl)piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-A’,A-dimethyl-7 / f-pyrrolo[2,3-^- pyrimidine-6-carboxamide A 172;7-cyclopentyl-2-((5-(4-(4-(2-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4- yl)ethyl)cyclohexyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A7-dimethyl-7J7-pyrrolo[2,3-< / |- pyrimidine-6-carboxamide A173;7-cyclopentyl-2-((5-(4-(l-(2-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4- yl)ethyl)piperidin-4-yl)piperazin-l -yl)pyridin-2-yl)amino)-A,Ar-dimethyl-7 / 7-pyrrolo[2,3-6Q- pyrimidine-6-carboxamide A174;7-cyclopentyl-2-((5-(4-(2-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[4,4'- bipiperidin]-l-yl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A-dimethyl-7Af-pyrrolo[2,3-J]- pyrimidine-6-carboxamide A175;7-cyclopentyl-2-((5-(4-(2-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'- bipiperidin]-4-yl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-A / / -dimethyl-7 / 7-pyrrolo[2,3-J]- pyrimidine-6-carboxamide A176;7-cyclopentyl-2-((5-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethyl)piperazin-l-yl)pyridin-2-yl)amino)-N,N-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6- carboxamide A177;7-cyclopentyl-2-((5-(4-(2-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A7-dimethyi-7 / / -pyrrolo[2,3-c / ]pyrimidine-6-carboxamide Al 78;7-cyclopentyl-2-((5-(4-(l-(3-(4-(2,6-dioxopiperidin-3-yl)phenoxy)propyl)- piperidin-4-yl)piperazin-l -yl)pyridin-2-yl)amino)-A,ALdimethyl-7 / 7-pyrrolo[2,3-< / jpyrimidine-6- carboxamide A179;7-cyclopentyl-2-((5-(4-(3-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- propyl)piperazin-l-yl)pyridin-2-yl)amino)-A7,A-dimetliyl-77 / -pyrrolo[2,3-67]pyrimidine-6- carboxamide A180;7-cyclopentyl-2-((5-(4-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperidin-4- yl)cyclohexyl)piperazin-l-yl)pyridin-2-yl)amino)-yV,A-dimethyl-72 / -pyrrolo[2,3-6Z]pyrimidine-6- carb oxami de A 181 ;7-cyclopentyl-2-((5-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)-[l,4'-bipiperidin]- r-yl)pyridin-2-yl)amino)-Ar,Ar-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide A182;7-cyclopentyl-2-((5-((r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]-4- yl)methyl)pyridin-2-yl)amino)-A7,A7-dimethyl-7Ar-pyiTolo[2,3-t7]pyrimidine-6-carboxamide A183;7-cyclopentyl-2-((5-((r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[4,4'-bipiperidin]-l- yl)methyl)pyridin-2-yl)amino)-A / ,A’-dimethyl-7 / 7-pyrrolo[2,3-^pyrimidine-6-carboxamide A184;7-cyclopentyl-2-((5-((4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)methyl)pyridin-2-yl)amino)-A7,ALdimethyl-7 / / -pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A185;7-cyclopentyl-2-((5-((r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]-4- yl)oxy)pyridin-2-yl)amino)-A',A7-dimethyl-7 / / -pyrrolo[2,3-J]pyrimidine-6-carboxamide A186;7-cyclopentyl-2-((5-((r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]-4- yl)methoxy)pyridin-2-yl)amino)-Az,A-dimethyl-7 / / -pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A187;7-cyclopentyl-2-((5-(2-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[4,4f-bipiperidin]- l-yl)ethyl)pyridin-2-yl)amino)-A7,A-dimethyl-7 / / -pyrrolo[2,3-< / |pyrimidine-6-carboxamide A188;7-cyclopentyl-2-((5-(2-(l'-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]- 4-yl)ethyl)pyridin-2-yl)amino)-A7,Air"dimethyl-7 / f-pyrrolo[2,3-c7|pyrimidine-6-carboxamideA189;7-cyclopentyl-2-((5-(2-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)ethyl)pyridin-2-yl)amino)-A;A-dimethyl-7 / f-pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A190;7-cyclopentyl-2-((5-(2-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[4,4'-bipiperidin]- l-yl)ethoxy )pyri din-2 -yl)amino)-A'’,jV-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide A191;7-cyclopentyl-2-((5-(2-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]- 4-yl)ethoxy)pyri din-2 -yi)amino)-A,A-dimethyi-7 / / -pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A192;7-cyclopentyl-2-((5-(2-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)ethoxy)pyridin-2-yl)amino)-Az,A-dimethyl-7 / / -pyrrolo[2,3-tZ]pyrimidine-6- carboxamide A193;7-cyclopentyl-2-((5-(4-(l-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- methyl)azetidin-3-yl)piperazin-l-yi)pyridin-2-yl)amino)-A7,iV-dimethyl-7 / f-pyrrolo[2,3-^- pyrimidine-6-carboxamide A194;7-cyclopentyl-2-((5-(4-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-7V,Az-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6- carboxamide Al 95;7-cyclopentyi-2-((5-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- [l,4'-bipiperidin]-r-yl)pyridin-2-yl)amino)-A’,A;-dimethyl-7Ar-pyrrolo[2,3-Jjpyrimidine-6- carboxamide A196;7-cyclopentyl-2-((5-(4-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- cyclohexyl)piperazin-l-yi)pyridin-2-yl)amino)-AyA'-dimethyl-77f-pyrrolo[2,3-< / |pyrimidine-6- carboxamide A197;7-cyclopentyl-2-((5-(4-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- cyclohexyl)piperidin-l-yl)pyridin-2-yl)amino)-A,Ar-dimethyl-7ZApyrrolo[2,3-^]pyrimidine-6- carboxamide Al 98;7-cy clopentyl-2-((5 -(4-( 1 -(3 -(3 -(2, 6-dioxopiperi din-3 -yl)phenoxy)propyl)- piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A’-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6- arboxamide A199;7-cyclopentyl-2-((5-((4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-1 -yl)methyl)pyridin-2-yl)amino)-A / ,A-dimethyl-7ZApyrrolo[2, 3 -t / Jpyrim idine-6- carboxamide A200;7-cyclopentyl-2-((5-(2-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin- 1 -y l)ethyl)pyridin-2-yl)amino)-7V,jV-dimethyl -7 / 7-pyrrol o[2,3 -cfjpy rimi dine-6- carboxamide A201:7-cyclopentyl-2-((5-(3-(l'-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[4,4'-bipiperidin]- l-yl)propyl)pyridin-2-yl)amino)-A,A-dimethyl-7 / 7-pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A202;7-cyclopentyl-2-((5-(3-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)propyl)pyridin-2-yl)amino)-jV,A / -dimethyl-7 / / -pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A203;7-cyclopentyl-2-((5-(3-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)propyl)pyridin-2-yl)amino)-Ay / V-dimethyl-7H-pyrrolo[2,3-^pyrimidine-6- carboxamide A204:7-cyclopentyl-2-((5-(3-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]-4-yl)propyl)pyridin-2-yl)amino)-A,A-dimethyl-7 / 7-pyrrolo[2,3-t / |pyrimidine-6-carboxamide A205;7-cy cl opentyl-2-(( 5 -(2-(4-(4-(3 -(2, 6-dioxopiperidin-3 -yl)pheny l)piperazin- 1 -y I)- piperidin-l-yl)ethyl)pyridin-2-yl)amino)-yV,2V-dimethyl-7J / -pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A206;7-cyclopentyl-2-((5-((25)-2-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l- yl)methyl)morpholino)pyridin-2-yl)amino)-Ar,A'-dimethyl-7 / / -pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A207:7-cyclopentyl-2-((5-((2A)-2-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l- yl)methyl)morpholino)pyridin-2-yl)amino)-A7,A’-dimethyl-7 / / -pyrrolo[2,3-tZ]pyrimidine-6- carboxamide A208;7-cyclopentyl-2-((5-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l-yl)- piperidin-l-yl)pyridin-2-yl)amino)-jV,Ar-dimethyl-77 / -pyrrolo[2,3-J]pyrimidine-6-carboxamide A209;7-cyclopentyl-2-((5-((r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]-3yl)oxy)pyridin-2-yl)amino)-Ar,7'Z-dimethyl-7 / 7-pyrrolo[2,3-<7]pyrimidine-6-carboxamide A210;7-cyclopentyl-2-((5-((3-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)methyl)pyridin-2-yl)amino)-A / ,7V-dimethyl-7 / 7-pyrrolo[2,3-< / ]pyrimidine-6- carboxamide A211;7-cyclopentyl-2-((5-((r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[3,4'-bipiperidin]-l- yl)methyl)pyridin-2-yl)amino)-77,jV-dimethyl-7 / / -pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A212;7-cyclopentyl-2-((5-(2-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)ethoxy)pyridin-2-yl)amino)-yV,7V-dimethyl-72 / -pyrrolo[2,3-6Z]pyrimidine-6- carboxamide A213;7-cyclopentyl-2-((5-(4-((4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)methyl)piperidin-l-yl)pyridin-2-yl)amino)-A,JV-dimethyl-77 / -pyrrolo[2,3-<7]- pyrimidine-6-carboxamide A214;7-cyclopentyl-2-((5-(4-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- benzyl)piperazin-l-yl)pyridin-2-yl)amino)-A?,Ar-dimethyl-7 / f-pyrrolo[2,3"^pyrimidine-6- carboxamide A215;7-cyclopentyl-2-((5-(4-(4-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- methyl)phenyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A7-dimethyl-7J / -pyrrolo[2,3-t / ]pyrimidine- 6-carboxamide A216;7-cyclopentyi-2-((5-(4-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- methyl)piperazin-l-yl)pyridin-2-yl)amino)-A,,A;-dimethyl-7 / / -pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A217;7-cyclopentyl-2-((5-(l-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- methyl)piperidin-4-yl)pyridin-2-yl)amino)-A?,A'r-dimethyl-7 / f-pyrrolo[2,3-i / ]pyrimidine-6- carboxamide A218;7-cyclopentyl-2-((5-(4-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- methyl)piperidin-l-yl)pyridin-2-yl)amino)--A’,AT"dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6- carboxamide A219;7-cyclopentyl-2-((5-(4-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- methyl)piperidin-l-yl)pyridin-2-yl)amino)-AzrA'-dimethyl-7 / / -pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A220;7-cy cl opentyl-2-((5 -(4-(( 1 -(3 -(2, 6-di oxopiperi din-3 -yl )phenyl)piperi din-4-y 1 )- methyl)piperazin-l-yl)pyridin-2-y!)amino)-A / ,A-dimethyl-7Z7-pyrrolo[2,3-< / ]pyriniidiiie-6- carboxamide A221;7-cyclopentyl-2-((5-(l-((l-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- methyl)piperidin-4-yl)pyri din-2 -yl)amino)-A',A'r-dimethyl-777-pyrrolo[2,3-J_|pyrimidine-6- carboxamide A222:7-cyclopentyl-2-((5-(4-((4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- methyl)piperidin-l -yl)pyridin-2-yl)amino)-ATA-dimethyl-777-pyrrolo[2,3-< / ]pyrimidine-6- carboxamide A223;7-cyclopentyl-2-((5-(4-((4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- methyl)piperidin-l-yl)pyridin-2-yl)amino)-A7,Ar-dimethyl-7 / / -pyrrolo[2,3-^pyrimidine-6- carboxamide A224;7-cyclopentyl-2-((5-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]-r- yl)methy])pyridin-2-yl)amino)-A7,A7-dimethyl-7 / 7-pyiTolo[2,3-t / ]pyrimidine-6-carboxarnide A225;7-cyclopentyl-2-((5-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A?-dimethyl-7J / -pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A226;7-cy cl opentyl-2-(( 5 -( 1 -(2-(4-(4-(2, 6-di oxopiperi din-3 -yl)phenyl)piperi di n- 1 -yl)- ethyl)piperidin-4-yl)pyridin-2-yl)amino)-AT,7V-dimethyl-72 / -pyrrolo[2,3-J]pyrimidine-6- carboxamide A227;7-cyclopentyl-2-((5-(l-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethyl)piperidin-4-yl)pyridin-2-yl)amino)-A7,A-dimethyl-7 / / -pyrrolo[2,3-J]pyrimidine-6- carboxamide A228;7-cyclopentyl-2-((5-(l-(2-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethyl)piperidin-4-yl)pyri din-2 -yl)amino)-AT, A-dimethy I -7 / Z-pyrrol o[2,3 -t^pyrimi dine-6- carboxamide A229;7-cyclopentyl-2-((5-(4-(2-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,ALdimethyl-7J7-pyrrolo[2,3-< / |pyrimidine-6- carboxamide A230;7-cyclopentyl-2-((5-(4-(2-(l-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)-ethyl)piperazin-l-yl)pyridin-2-yl)amino)-A,A-dimethyl-7 / 7-pyrrolo[2,3-(7]pyrimidine-6- carboxamide A231;7-cyclopentyl-2-((5-(4-(2-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l -yl)- ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,Ar-dimethyl-7 / 7-pyrrolo[2,3-£ / ]pyrimidine-6- carboxamide A232;7-cyclopentyl-2-((5-(l-(2-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethyl)piperidin-4-yl)pyridin-2-yl)amino)-A';A-dimethyl-77 / -pyrrolo[2,3-6 / ]pyrimidine-6- carboxamide A233;7-cyclopentyl-2-((5-(l-(2-(l-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- ethyl)piperidin-4-yl)pyridin-2-yl)amino)-A,A-dimethyl-7H-pyrrolo[2,3-t7]pyrimidine-6- carboxamide A234;7-cy clopenty 1 -2-((5 -( 1 -(2-(4-(3 -(2, 6-dioxopiperidin-3 -yl)pheny l)piperazi n- 1 -y 1)- ethyl)piperidin-4-yl)pyridin-2-yl)amino)-A7,A-dimethyl-777-pyrrolo[2,3-t7]pyrimidine-6- carboxamide A235;7-cyclopentyl-2-((5-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]- r-yl)ethyl)pyridin-2-yl)amino)-A7,Ar-dimetliyl-7 / 7-pyrrolo[2,3-< / ]pyriniidine-6-carboxamide A236;7-cyclopentyl-2-((5-(r-(4-(2,6-dioxopiperidin-3-yl)phenethyl)-[4,4'-bipiperidin]- l-yl)pyridin-2-yl)amino)-Ar,A'r-dimethyl-7 / f-pyrrolo[2,3-fi(|pyrimidine-6-carboxamide A237;7-cyclopentyi-2-((5-(r-(4-(2,6-dioxopiperidin-3-yl)phenethyl)-[l,4'-bipiperidin]- 4-yl)pyridin-2-yl)amino)-Ar,A-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide A238;7-cyclopentyl-2-((5-(2-(4-(l-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin- 1 -y l)ethyl)pyridin-2-yl)amino)-A,Ar-dimethyl -7 / 7-pyrrol o [2, 3 -<7]pyrimi dine-6- carboxamide A239:7-cyclopentyi-2-((5-(2-(r-(3-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]-4-yl)ethyl)pyridin-2-yl)amino)-A’,Ar-dimethyl-7H-pyrrolo[2,3-t(]pyrimidine-6-carboxamide A240;7-cyclopentyl-2-((5-(2-(r-(3-(2,6-dioxopiperidin-3-yl)phenyl)-[4,4'-bipiperidin]- l-yl)ethyl)pyridin-2-yl)amino)-A^V-dimethyl-77 / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide A241;7-cyclopentyl-2-((5-(2-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]r-yl)ethyl)pyridin-2-yl)amino)-A'r,A'r-dimethyl-7 / / -pyrroio[2,3-«i]pyrimidine-6-carboxamide A242;7-cyclopentyl-2-((5-(2-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)ethoxy)pyridin-2-yl)amino)-AT2V-dimethyl-7 / f-pyrrolo[2,3-<7|pyrimidine-6- carboxamide A243;7-cy clopentyl-2-((5 -(2-(4-( 1 -(3 -(2, 6-dioxopiperi din-3 -yl)pheny l)pi p eri di n-4 -y 1 )- piperazin- 1 -yl)ethoxy)pyridin-2-yl)amino)-Ar,Ar-dimethyl -7 / 7-pyrrol o [2, 3 -<7]py rimi dine-6- carboxamide A244;7-cyclopentyl-7V,ALdimethyl-2-((5-(4-(l-(4-(3-methyl-2,6-dioxopiperidin-3-yl)- phenethyl)piperidin-4-yl)piperazin-l-yl)pyri din-2 -yl)amino)-7 / 7-pyrrolo[2,3-< / jpyrimidine-6- carboxamide A245;7-cyclopentyl-2-((5-(4-(2-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- ethyl)piperidin-l-yl)pyridin-2-yl)amino)-A7,A-dimethyl-7Af-pyrrolo[2,3-t7]pyrimidine-6- carboxamide A246;7-cyclopentyl-2-((5-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethyl)piperidin-l-yl)pyridin-2-yl)amino)-ApV-dimethyl-7#-pyrrolo[2,3-<7]pyriniidine-6- carboxamide A247;7-cyclopentyl-2-((5-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- ethyl)piperidin-l-yl)pyridin-2-yl)amino)-A,A-dimethyl-72 / -pyrrolo[2,3-tZ]pyrimidine-6- carboxamide A248;7-cyclopentyl-2-((5-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- propoxy)pyridin-2-yl)amino)-Ar,A-dimethyl-7Af-pyrrolo[2,3-tZ]pyrimidine-6-carboxamide A249;7-cyclopentyl-2-((5-(3-(l-(4-(2, 6-dioxopiperi din-3-yl)phenyl)piperidin-4-yl)- propoxy)pyridin-2-yl)amino)-AA,Ar-dimethyl-7JH-pyrrolo[2,3-«7]pyrimidine-6-carboxamide A250;7-cyclopentyi-2-((5-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethoxy)pyridin-2-yl)amino)-A’',Ar-dimethyi-7J7-pyrrolo[2,3-c / ]pyrimidine-6-carboxamide A251;7-cycl opentyl-2-((5-(2-(l-(4-(2, 6-dioxopiperi din-3 -yl)phenyl)piperi din-4-yl)- ethoxy)pyridin-2-yl)amino)-Ar,A-dimethyl-7 / / -pyrrolo[2,3-i / ]pyrimidine-6-carboxamide A252;7-cyclopentyl-2-((5-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)-4-fluoro-[l,4'- bipiperidin]-r-yl)pyridin-2-yl)amino)-A' / / -dimethyl-7 / 7-pyrrolo[2,3-J]pyrimidine-6- carboxamide A253;7-cyclopentyl-2-((5-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)pyridin-2-yl)amino)-A^V-dimethyl-72 / -pyrrolo[2,3-tZ]pyrimidine-6-carboxamide A254;7-cyclopentyl-2-((5-(4-(l-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)pyridin-2-yl)amino)-A / ,A''-dimethyl-7J? / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide A255;7-cyclopentyl-2-((5-(4-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)azetidin-3-yl)- methyl)piperazin-l-yi)pyridin-2-yl)amino)-7V,A7-dimethyl-7H-pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A256;7-cyclopentyl-2-((5-(4-((l-(3-(2,6-dioxopiperidin-3-yl)phenyl)azetidin-3-yl)- methyl)piperazin-l-yl)pyridin-2-yl)amino)-A,A-dimethyl-7Z7-pyrrolo[2,3-(7]pyrimidine-6- carboxamide A257;7-cyclopentyl-2-((5-(4-(2-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)azetidin-3-yl)- ethy l)piperazin- 1 -yl)pyridin-2-yl)amino)-;V,Az-dimethyl -777-pyrrol o[2,3 -djpyrimi dine-6- carboxamide A258:7-cyclopentyl-2-((5-(4-(2-(l-(3-(2,6-dioxopiperidin-3-yl)phenyl)azetidin-3-yl)- ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A?-dimethyl-7J7-pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A259;7-cyclopentyl-2-((5-(4-(l-(2-(4-(2,6-dioxopiperidin-3-yl)phenyl)-2,2-difluoro- ethyl)piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-A / ,Ar"dimethyl-7Z / -pyrrolo[2,3-t / j- pyrimidine-6-carboxamide A260;7-cyclopentyl-2-((5-(4-(l-(2-(3-(2,6-dioxopiperidin-3-yl)phenyl)-2,2-difluoro- ethyl)piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-Af,A’-dimethyl-7 / / -pyrrolo[2,3-t(|- pyrimidine-6-carboxamide A261;7-cyclopentyi-2-((5-(4-(l-(2-(4-(2,6-dioxopiperidin-3-yl)phenyl)-2,2-difluoro- ethyl)azetidin-3-yl)piperazin-l-yl)pyridin-2-yl)amino)-A'’,A7-dimethyl-7JH-pyrroio[2,3-<7]- pyrimidine-6-carboxamide A262;7-cyclopentyl-2-((5-(4-(l-(2-(3-(2,6-dioxopiperidin-3-yl)phenyl)-2,2-difluoro- ethyl)azetidin-3-yl)piperazin-l-yl)pyridin-2-yl)amino)-Ar2V-dimethyl-7 / f-pyrrolo[2,3-(7]- pyrimidine-6-carboxamide A263;7-cyclopentyl-2-((5-(4-(l-(4-(2,6-dioxopiperidin-3-yl)benzyl)azetidin-3-yl)-piperazin-l-yl)pyridin-2-yl)amino)-Ar,A’-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide A264;7-cyclopentyl-2-((5-(4-(l-(3-(2,6-dioxopiperidin-3-yl)benzyl)azetidin-3-yl)- piperazin-l-yl)pyridin-2-yl)amino)-A'r,A-dimethyl-7 / Z-pyrrolo[2,3-if|pyrimidine-6-carboxamide A265;7-cyclopentyl-2-((5-(4-(3-(2,6-dioxopiperidin-3-yl)phenethyl)-4-fluoro-[l,4'- bipiperidin]-r-yl)pyridin-2-yl)amino)-A / ,jV-dimethyl-777-pyrrolo[2,3-< / ]pyrimidine-6- carboxamide A266;7-cyclopentyl-2-((5-(4-(4-(2,6-dioxopiperidin-3-yl)benzyl)-4-fluoro-[l,4'- bipiperidin]-r-yl)pyridin-2-yl)amino)-A / ,Ar-dimethyl-7 / / -pyrrolo[2,3-^pyrimidine-6- carboxamide A267;7-cyclopentyl-2-((5-(4-(3-(2,6-dioxopiperidin-3-yl)benzyl)-4-fluoro-[l,4'- bipiperidin]-r-yl)pyridin-2-yl)amino)-A,jV-dimethyl-7 / / -pyrrolo[2,3-«7]pyrimidine-6- carboxamide A268;7-cyclopentyl-2-((5-(4-(3-(4-(2,6-dioxopiperidin-3-yl)phenethyl)-3-fluoro- azetidin-l-yl)piperidin-l-yl)pyridin-2-yl)amino)-A',Ar"dimetliyl-7 / 7-pyrrolo[2,3-< / ]pyriniidine-6- carboxamide A269;7-cyclopentyl-2-((5-(4-(3-(3-(2,6-dioxopiperidin-3-yl)phenethyl)-3-fluoro- azetidin-l-yl)piperidin-l-yl)pyridin-2-yl)amino)-A,A'’-dimethyl-7 / f-pyrrolo[2,3-^pyrimidine-6- carboxamide A270;7-cyclopentyl-2-((5-(3-(l-(2-(4-(2,6-dioxopiperidin-3-yl)phenyl)-2,2-difluoro— ethyl)piperidin-4-yl)azetidin-l-yl)pyridin-2-yl)amino)-A7,Af-dimethyl-7 / / -pyrrolo[2,3-tZ]- pyrimidine-6-carboxamide A271 ;7-cyclopentyl-2-((5-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l-yl)- azetidin-l-yl)pyridin-2-yl)amino)-A’,A-dimethyl-7 / 7-pyrrolo[2,3-< / jpyrimidine-6-carboxamide A272;7-cyclopentyl-2-((5-(3-(4-(3-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l-yl)- azetidin-l-yl)pyridin-2-yl)amino)-AT,A-dimethyl-7 / f-pyrrolo[2,3-tf|pyrimidine-6-carboxamide A273;7-cyclopentyl-2-((5-(3-(4-(4-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yl)- azetidin-l-yl)pyridin-2-yl)amino)-A7,A’-dimethyl-77Z-pyrrolo[2,3-<7]pyrimidine-6-carboxamideA274;7-cyclopentyl-2-((5-(3-(4-(3-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yl)- azeti din-1 -yl)pyridin-2-yl)amino)-A',A?-dimethyl-7H-pyrrolo[2,3-c / ]pyrimidine-6-carboxamideA275;7-cyclopentyl-2-((5-(4-(3-(4-(2,6-dioxopiperidin-3-yl)benzyl)-3-fluoroazetidin-l- yl)piperidin-l-yl)pyridin-2-yl)amino)-Ar,AMimethyl-7AApyrrolo[2,3-J]pyrimidine-6- carboxamide A276;7-cyclopentyl-2-((5-(4-(3-(3-(2,6-dioxopiperidin-3-yl)benzyl)-3-fluoroazetidin-l- yl)piperidin-l-yl)pyridin-2-yl)amino)-A7,ALdimethyl-7Z / -pyrrolo[2,3-^pyrimidine-6- carboxamide A277;7-cyclopentyl-2-((5-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperidin-l-yl)- azetidin-l-yl)pyridin-2-yl)amino)-A’,A-dimethyl-7JHr-pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A278;7-cyclopentyl-2-((5-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)-4-fluoro- piperidin- 1 -yl)azetidin- 1 -yl)pyridin-2-yl)amino)-Ar,A-dimethyl-7Af-pyrrolo[2,3 - J]pyrimidine-6- carboxamide A279;7-cyclopentyl-2-((5-(3-(4-(3-(2,6-dioxopiperidin-3-yl)phenethyl)piperidin-l-yl)- azetidiii-l-yl)pyridin-2-yl)aniino)-Ar,A7-dimethyl-7J / -pyrrolo[2,3-cf|pyrimidine-6-carboxamide A280;7-cyclopentyi-2-((5-(3-(4-(3-(2,6-dioxopiperidin-3-yl)phenethyl)-4-fluoro- piperidin-l-yl)azetidin-l-yl)pyridin-2-yl)amino)-A’,7V-dimethyl-7Z / -pyrrolo[2,3-J]pyrimidine-6- carboxamide A281;7-cyclopentyl-2-((5-(3-(4-(3-(2,6-dioxopiperidin-3-yl)benzyl)-4-fluoropiperidin- l-yl)azetidin-l-yl)pyridin-2-yl)amino)-A,A / -dimethyl-7 / f-pyrrolo[2,3-< / |pyrimidine-6- carboxamide A282;7-cyclopentyl-2-((5-(3-(4-(4-(2,6-dioxopiperidin-3-yl)benzyl)-4-fluoropiperidin- l-yl)azetidin-l-yl)pyridin-2-yl)amino)-A^V-dimethyl-77 / -pyrrolo[2,3-t7]pyrimidine-6- carboxamide A283;7-cyclopentyl-2-((5-(4-((3-(4-(2,6-dioxopiperidin-3-yl)phenyl)azetidin-l-yl)- methyl)-4-fliioropiperidin-l-yl)pyridin-2-yl)amino)-A'',7V-dimethyl-7 / 7-pyrrolo[2,3-tf|pyrimidine- 6-carboxamide A284;7-cyclopentyl-2-((5-(4-((3-(3-(2,6-dioxopiperidin-3-yl)phenyl)azetidin-l -yl)- methyl)-4-fluoropiperidin-l-yl)pyri din-2 -yl)amino)-A’,Ar-dimethyl-7Ar-pyrrolo[2,3-^]pyrimidine- 6-carboxamide A285,7-cyclopentyl-2-((5-(l-((l-(3-(2,6-dioxopiperidin-3-yl)phenyl)-4-fluoropiperidin- 4-yl)methyl)piperidin-4-yl)pyridin-2-yl)amino)-JV^V-dimethyl-7 / / -pyrrolo[2,3-<^pyrimidine-6- carboxamide A286:7-cyclopentyl-2-((5-(l-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)-4-fluoropiperidin- 4-yl)methyl)piperidin-4-yl)pyridin-2-yl)amino)-A'r,Ar-dimethyl-7Af-pyrrolo[2,3-^pyrimidine-6- carboxamide A287;7-cyclopentyl-2-((5-(4-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- methyl)-4-fluoropiperidin-l-yl)pyri din-2 -yl)amino)-A’,Ar-dimethyl-7 / / -pyrrolo[2,3-d]pyrimidine- 6-carboxamide A288;7-cyclopentyl-2-((5-(4-((4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- methyl)-4-fluoropiperi din-1 -yl)pyridin-2-yl)amino)-ArfAr-dimethyl-71 / -pyrrolo[2,3-< / ]pyrimidine- 6-carboxamide A289;7-cyclopentyl-2-((5-(4-(2-(l-(4-(2,6-dioxopiperidin-3-yl)-3-fluorophenyl)- piperidin-4-yl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-7V,Ar-dimethyl-7H-pyrrolo[2,3-(fj- pyrimidine-6-carboxamide A290;7-cy cl opentyl-2-(( 5 -(4-(2-( 1 -(4-(2, 6-dioxopiperidi n-3 -yl)-2-fluoropheny I )- piperidin-4-yl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-A / ,Ar-dimethyl-7Z / -pyrrolo[2,3-t / j- pyrimidine-6-carboxamide A291;2-((5-(4-(2-(l-(3-chloro-4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)ethyl)- piperazin-l-yl)pyridin-2-yl)amino)-7-cyclopentyl-Ar,A-dimethyl-7JE / -pyrrolo[2,3-6Z]pyrimidine-6- carboxamide A292:2-((5-(4-(2-(l-(2-chloro-4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)ethyl)- piperazin-l-yl)pyridin-2-yl)amino)-7-cyclopentyl-A,A-dimethyl-7H-pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A293;7-cyclopentyl-2-((5-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazm-l-yl)- azetidin-l-yl)pyridin-2-yl)amino)-AT,A-dimethyl-7JH-pyrrolo[2,3-<7|pyrimidine-6-carboxamide A294;7-cyclopentyl-2-((5-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)azetidin-3-yl)-piperazin-l-yl)pyridin-2-yl)amino)-Ar,A’-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide A295;7-cyclopentyl-2-((5-(3-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- azetidin-l-yl)pyridin-2-yl)amino)-A7,Ar-dimethyl-7 / 7-pyrrolo[2,3-c / ]pyrimidine-6-carboxamide A296;7-cyclopentyl-2-((5-(4-(2-(l-(3-(2,6-dioxopiperidin-3-yl)-5-fluorophenyl)- piperidin-4-yl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-A',7V-dimethyl-7 / 7-pyrrolo[2,3-c7j- pyrimidine-6-carboxamide A297;7-cyclopentyl-2-((5-(4-(2-(l-(3-(2,6-dioxopiperidin-3-yl)-4-fluorophenyl)- piperidin-4-yl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A'-dimethyl-7 / 7-pyrrolo[2,3-i7]- pyrimidine-6-carboxamide A298;7-cyclopentyl-2-((5-(4-(4-(2,6-dioxopiperidin-3-yl)-3-fluorophenethyl)-4-fluoro-[ 1 ,4' -bipiperi din] -■ 1 '-yl)pyridin-2-yl)amino)-A,Ar-dimethyl-727-pyrrolo[2,3 - J]pyrimidine-6- carboxamide A299; or7-cyclopentyl-2-((5-((r-(3-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]-4- yl)methoxy)pyridin-2-yl)amino)-A7,A-dimethyl-7 / Apyrrolo[2,3-JJpyrimidine-6-carboxamide A300; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0260] In yet another embodiment, provided herein is a compound of:7-cyclopentyl-2-((5-(3-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- l,l-difluoroethyl)azetidin-l-yl)pyridin-2-yl)amino)-A7V-dimethyl-7JH-pyrrolo[2,3-d]pyrimidine- 6-carboxamide A351;7-cy cl opentyl-2-((5 -(4-(2-( 1 -(5 -(2, 6-dioxopiperidi n-3 -yl)-2-fluoropheny I )- piperidin-4-yl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,Ar-dimethyl-7 / f-pyrrolo[2,3-d]- pyrimidine-6-carboxamide A352; or7-cyclopentyl-2-((5-(4-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenethyl)-4-fluoro- [l,4'-bipiperidin]-l '-yl)pyridin-2-yl)amino)-Ar,A-dimethyl-7 / / -pyrrolo[2,3-tZ]pyrimidine-6- carboxamide A353: or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or apharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0261] In yet another embodiment, provided herein is a compound of:7-cyclopentyl-2-((4-((2-(4-(2-(3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)- phenoxy)acetyl)piperazin-l-yl)ethyl)carbamoyl)phenyl)amino)-Az,A7-dimethyl-7J7-pyrrolo[2,3-6 / ]- pyrimidine-6-carboxamide A401;7-cyclopentyl-2-((4-((4-(4-(2-(3-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)- phenoxy)acetyl)piperazin-l-yl)butyl)carbamoyl)phenyl)amino)-AAV-dimethyl-77 / -pyrrolo[2,3-< / |pyrimidine-6-carboxamide A402;7-cyclopentyl-2-((4-((6-(4-(2-(3-(2,4-dioxotetrahydropyrimidin4(2 / / )-yl)- phenoxy)acetyl)piperazin-l-yl)hexyl)carbamoyl)phenyl)amino)-Az / / -dimethyl-7 / 7-pyrrolo[2,3- <7]pyrimidine-6-carboxamide A403;7-cyclopentyl-2-((4-((2-(4-(2-(4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)- phenoxy)acetyl)piperazin-l-yl)ethyl)carbamoyl)phenyl)amino)-Az,A7-dimethyl-7Ar-pyrrolo[2,3-£ / ]- pyrimidine-6-carboxamide A404;7-cyclopentyl-2-((4-((4-(4-(2-(4-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)- phenoxy)acetyl)piperazin-l-yl)butyl)carbamoyl)phenyl)amino)-A7,Az-dimethyl-7H-pyrrolo[2,3-< / |pyrimidine-6-carboxamide A405; or7-cyclopentyl-2-((4-((6-(4-(2-(4-(2,4-dioxotetrahydropyrimidin-l(22 / )-yl)- phenoxy)acetyl)piperazin-l-yl)hexyl)carbamoyl)phenyl)amino)-Az,Ar-dimethyl-7 / Apyrrolo[2,3-^pyrimidine-6-carboxamide A406; or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0262] In yet another embodiment, provided herein is a compound of:7-cyclopentyl-2-((4-(4-(3-(2,4-dioxotetrahydropyrimidin-l(2Z / )-yl)phenyl)- piperazin-l-yl)phenyl)amino)-A’,Ar-dimetliyl-7 / Apyrrolo[2,3-< / ]pyrimidine-6-carboxamide A407;7-cyclopentyl-2-((5-(4-(4-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)phenyl)- piperazin-l-yl)pyridin-2-yl)amino)-AjV-dimethyl-7 / / -pyrrolo[2,3-t(|pyrimidine-6-carboxaniideA408;7-cyclopentyl-2-((4-(4-(4-(2,4-dioxotetrahydropyrimidin-l(2 / 7)-yl)benzyl)- piperazin- 1 -yl)phenyl)amino)-A,Ar-dimethyl-777-pyrrolo[2,3 -tZ]pyrimidine-6-carboxamide A409;7-cyclopentyl-2-((4-(4-(4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenethyl)- piperazin-l-yl)phenyl)amino)-A?',A / -dimethyl-7 / f-pyrrolo[2,3-^pyrimidine-6-carboxaniide A410;7-cyclopentyl-2-((5-(4-(2-(4-(2,4-dioxotetrahydropyrimidin-l(22 / )-yl)phenoxy)- ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,Ar-dimethyl-7 / / -pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A411;7-cyclopentyl-2-((4-(2-(4-(4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenyl)- piperazin-l-yl)ethyl)phenyl)amino)-AAV-dimethyl-7 / 7-pyrrolo[2,3-6f]pyrimidine-6-carboxamide A412;7-cyclopentyl-2-((4-(2-(4-(3-(2,4-dioxotetrahydropyrimidin-l(22 / )-yl)phenyl)- piperazin-l-yl)ethyl)phenyl)amino)-Ar,A’-dimethyl-7 / 7-pyrrolo[2,3-tf|pyrimidine-6-carboxamide A413;7-cyclopentyl-2-((5-((4-(4-(2,4-dioxotetraliydropyrimidin-l(2 / / )-yl)phenyl)- piperazin-l-yl)methyl)pyridin-2-yl)amino)-Ar,Ar-dimethyl-727-pyrrolo[2,3-( / ]pyrimidine-6- carboxamide A414;7-cyclopentyl-2-((5-(2-(4-(4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenyl)- piperazin-l-yl)ethoxy)pyridin-2-yl)amino)-Ar,A7-diniethyl-7 / Apyrrolo[2,3-t(|pyrimidine-6- carboxamide A415;7-cyclopentyl-2-((4-(2-(4-(4-(2,4-dioxotetrahydropyrimidin-l(2J / )-yl)phenyl)- piperazin-l-yl)ethoxy)phenyl)amino)-7V,Ar-dimethyl-7 / f-pyrrolo[2,3-^pyrimidine-6- carboxamide A416;7-cyclopentyl-2-((4-(2-(4-(3-(2,4-dioxotetrahydropyrimidin-l(2#)-yl)phenyl)- piperazin-l-yl)ethoxy)phenyl)amino)-A,AMimethyl-7#-pyrrolo[2,3-^pyrimidine-6- carb oxami de A417;7-cyclopentyl-2-((4-(2-(4-(4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)benzyl)- piperaziii-l-yl)ethoxy)phenyl)amino)"A^V-dimethyl-7 / / -pyrrolo[2,3"^pyrimidine-6- carboxamide A418;7-cyclopentyl-2-((5-((4-(3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenyl)- piperazin- 1 -yl)methyl)pyridin-2-yl)ammo)-Ar, AMimethy I -7 / Apyrrol o[2,3 -d]pyrimi dine-6- carboxamide A419;7-cyclopentyl-2-((4-(4-( 1 -(4-(2,4-dioxotetrahydropyrimidin- 11 )pheny 1)- piperidin-4-yl)piperazin-l-yl)phenyl)amino)-Ar,A7-dimethyl-7 / f-pyrrolo[2,3-^pyrimidine-6-carboxamide A420;7-cyclopentyl-2-((4-(4-( 1 -(3-(2,4-dioxotetrahydropyrimidin- 1 (2 / 7)-yl)phenyl)- piperidin-4-yl)piperazin-l -yl)phenyl)amino)-A',A?-dimethyl-7 / f-pyrrolo[2,3-c / ]pyrimidine-6- carboxamide A421;7-cyclopentyl-2-((4-(2-(4-(4-(2,4-dioxotetrahydropyrimidin-l(27 / )-yl)benzyl)- piperazin-l-yl)ethyl)phenyl)amino)-Ar,A7-dimethyl-7 / 7-pyrrolo[2,3-<7]pyrimidine-6-carboxamide A422;7-cyclopentyl-2-((4-(2-(4-(3-(2,4-dioxotetrahydropyrimidin-l(22 / )-yl)benzyl)- piperazin-l-yl)ethyl)phenyl)amino)-A!',A’-dimethyl-7 / / -pyrrolo[2,3--t7]pyrimidine-6-carboxamide A423;7-cyclopentyl-2-((4-(2-(4-(3-(2,4-dioxotetrahydropyrirnidin-l(277)-yl)benzyl)- piperazin-l-yl)ethoxy)phenyl)amino)-Ar,A-dimethyl-7Z / -pyrrolo[2,3-^]pyrimidine-6- carboxamide A424;7-cyclopentyl-2-((4-(2-(4-(4-(4-(2,4-dioxotetrahydropyrimidin-l(277)-yl)phenyl)- piperaziii-l-yl)piperidin-l-yl)ethyl)phenyl)amino)-ArJV-dimetliyl-7H-pyrrolo[2J-J]pyrimidine- 6-carboxamide A425,7-cyclopentyl-2-((4-(2-(4-(4-(3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenyl)- piperazin-l-yl)piperidin-l-yl)ethyl)phenyl)amino)-Ar,Az-dimethyl-7 / / -pyrrolo[2,3-t / ]pyrimidine- 6-carboxamide A426;7-cyclopentyl-2-((4-(2-(4-(4-(4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenyl)- piperazin-l-yl)piperidin-l-yl)ethoxy)phenyl)amino)-2V,A / -diraethyl-7 / / -pyrrolo[2,3-<7]pyrimidine- 6-carboxamide A427;7-cyclopentyl-2-((4-(4-(l-(4-(2,4-dioxotetrahydropyrimidin-l(21 / )-yl)phenethyl)- piperidin-4-yl)piperazin-l-yl)phenyl)amino)-A,ALdimethyl-77f-pyrrolo[2,3-<7]pyrimidine-6- carboxamide A428;7-cyclopentyl-2-((4-(4-(l-(3-(2,4-dioxotetrahydropyrimidin-l(22 / )-yl)phenethyl)- piperidin-4-yl)piperazin-l-yl)phenyl)amino)-Ar,A7-dimethyl-7J / -pyrrolo[2,3<(|pyrimidine-6- carboxamide A429;7-cyclopentyl-2-((5-(4-(l-(4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)benzyl)- piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A’-dimethyl-72 / -pyrrolo[2,3-<7]pyrimidine-6- carboxamide A430;7-cyclopentyl-2-((4-(4-((l-(4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenyl)- piperidin-4-yl)methyl)piperazin-l-yl)phenyl)amino)-jV,A7-dimethyl-72 / -pyrrolo[2,3-<Z]pyrimidine- 6-carboxamide A431,7-cyclopentyl-2-((4-(4-((l-(3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenyl)- piperidin-4-yl)methyl)piperazin-l-yl)phenyl)amino)-A’,A?-dimethyl-7 / / -pyrrolo[2,3-tZ]pyrimidine- 6-carboxamide A432;7-cyclopentyl-2-((4-(4-(2-(4-(4-(2,4-dioxotetrahydropyrimidin-l(2Ar)-yl)phenyl)- piperidin-l-yl)ethyl)piperazin-l-yl)phenyl)amino)-Ar,A7-dimethyl-777-pyrrolo[2,3-tZ]pyrimidine- 6-carboxamide A433; or7-cyclopentyl-2-((4-(4-(2-(4-(3-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)phenyl)- piperidin- 1 -yl)ethyl)piperazin- 1 -yl)phenyl)amino)-Ar,Ar-dimethyl-7Z / -pyrrolo[2,3 -<7]pyrimidine- 6-carboxamide A434; or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0263] In yet another embodiment, provided herein is a compound of:7-cyclopentyl-2-((5-(4-(l-(4-(2,4-dioxotetrahydropyrimidin-l(2 / 7)-yl)phenethyl)- piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-A^A7-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6- carboxamide A435;2-((5-(4-(2-(l-(3-chloro-4-(2,4-dioxotetrahydropyrimidin-l(2 / f)-yl)phenyl)- piperidin-4-yl)ethyl)piperazin-l -yl)pyridin-2-yl)amino)-7-cyclopentyl-Af,Ar-dimethyl-7H- pyrrolo[2,3-iZ]pyrimidine-6-carboxamide A436;7-cyclopentyl-2-((5-(4-(( 1 -(4-(2,4-dioxotetrahydropyrimidin- 1 (277r)-yl)phenyl)- piperidin-4-yl)methyl)piperazin-l-yl)pyridin-2-yl)amino)-A",AMimethyl-77 / -pyrrolo[2,3-i / |- pyrimidine-6-carboxamide A 437;2-((5-(4-((l-(3-chloro-4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenyl)- piperidin-4-yl)methyl)piperazin-l-yl)pyridin-2-yl)amino)-7-cyclopentyl-A?,Az-dimethyl-7 / f- pyrrolo[2,3-J]pyrimidine-6-carboxamide A438;7-cyclopentyl-2-((5-(4-(l-(4-(2,4-dioxotetrahydropyrimidin-l(2J / )-yl)phenyl)- piperidin-4-yl)piperazin-l-yl)pyri din-2 -yl)amino)-A',7V-dimethyl-7H-pyrrolo[2,3-J_|pyrimidine-6- carboxamide A439; or2-((5-(4-(l-(2-(3-chloro-4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenyl)-2,2-difluoroethyl)piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-7-cyclopentyl-A’,A7-dimethyl-77f- pyrrolo[2,3-tZ]pyrimidine-6-carboxamide A440; or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0264] In yet another embodiment, provided herein is a compound of:7-cyclopentyl-2-((4-((2-(4-(2-((3-(2,6-dioxopiperidin-3-yl)-l-methyl-17 / -indazol- 7-yl)oxy)acetyl)piperazin-l-yl)ethyl)carbamoyl)phenyl)amino)-A",A'-dimethyl-7 / 7-pyrrolo[2,3-t7]- pyrimidine-6-carboxamide A501;7-cyclopentyl-2-((4-((4-(4-(2-((3-(2,6-dioxopiperidin-3-yl)-l-methyl-l / / -indazol- 7-yl)oxy)acetyl)piperazin-l-yl)butyl)carbamoyl)phemyl)amino)-A’,AMimethyl-7 / / -pyrrolo[2,3- <7]pyrimidine-6-carboxamide A502;7-cyclopentyl-2-((4-((6-(4-(2-((3-(2,6-dioxopiperidin-3-yl)-l-methyl-lAf-indazol-7-yl)oxy)acetyl)piperazin-l-yl)hexyl)carbamoyl)phenyl)amino)-A';A’-dimethyl-7.H-pyrrolo[2,3- <7]pyrimidine-6-carboxamide A503;7-cyclopentyl-2-((4-((2-(4-(2-((3-(2,6-dioxopiperidin-3-yl)-l-methyl-177-indazol- 6-yl)oxy)acetyl)piperazin-l-yl)ethyl)carbamoyl)phenyl)amino)-A\AMimethyl-777-pyrrolo[2,3-tZ]- pyrimidine-6-carboxamide A504;7-cyclopentyl-2-((4-((4-(4-(2-((3-(2,6-dioxopiperidin-3-yl)-l-methyl-l / 7-indazol-6-yl)oxy)acetyl)piperazin-l-yl)butyl)carbamoyl)phenyl)amino)-A’,Ar-dimethyl-7 / / -pyrrolo[2,3- t / ]pyrimidine-6-carboxamide A505; or7-cyclopentyl-2-((4-((6-(4-(2-((3-(2,6-dioxopiperidin-3-yl)-l-methyl-17 / -indazol-6-yl)oxy)acetyl)piperazin-l-yl)hexyl)carbamoyl)phenyl)amino)-A^V-dimethyl-7 / f-pyrrolo[2,3- <7]pyrimidine-6-carboxamide A506; or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0265] In yet another embodiment, provided herein is a compound of:7-cyclopentyl-2-((4-((2-(4-(2-((3 -(2,4-dioxotetrahydropyrimidin- 1 (2 / / )-y 1)- 1 - methyl- 1 / f-indazol -7-yl)oxy)acetyl)piperazin- 1 -yl)ethyl)carbamoyl)phenyl)amino)-7V, A^- dimethyl-7A7-pyrrolo[2,3-d]pyrimidine-6-carboxamide A551;7-cyclopentyl-2-((4-((4-(4-(2-((3-(2,4-dioxotetrahydropyrimidin-l(2Ar)-yl)-l-methyl-177-indazol-7-yl)oxy)acetyl)piperazin-l -yl)butyl)carbamoyl)phenyl)amino)-A',,Ar- dimethyl-7 / 7-pyrrolo[2,3-< / ]pyriniidiiie-6-carboxamide A552;7-cyclopentyl-2-((4-((6-(4-(2-((3-(2,4-dioxotetrahydropyrimidin-l(2A / )-yl)-l- methyl- lAT-indazol-7-yl)oxy)acetyl)piperazin- 1 -yl)hexyl)carbamoyl)phenyl)amino)-A77- dimethyl-7H-pyrrolo[2,3-t7]pyrimidine-6-carboxamide A553;7-cyclopentyl-2-((4-((2-(4-(2-((3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)-l- methyl-lJH-indazol-6-yl)oxy)acety4)piperazin-l-yl)ethyl)carbamoyl)phenyl)amino)-A7,Az- dimethyl-7Zf-pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A554;7-cyclopentyl-2-((4-((4-(4-(2-((3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)-l- methyl-177-indazol-6-yl)oxy)acetyl)piperazin-l -yl)butyl)carbamoyl)phenyl)amino)-A7,Ar- dimethyl-7 / 7-pyrrolo[2,3-< / |pyrimidine-6-carboxamide A555; or7-cyclopentyl-2-((4-((6-(4-(2-((3-(2,4-dioxotetrahydropyrimidin-l(22 / )-yl)-l- m ethyl- 17 / -indazol-6-yl)oxy)acetyl)piperazin- 1 "yl)hexyl)carbamoyl)phenyl)amino)-A,A“ dimethyl-7H-pyrrolo[2,3-^pyrimidine-6-carboxamide A556; or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0266] In yet another embodiment, provided herein is a compound of:7-cyclopentyl-2-((5-(4-(2-(3-(2,4-dioxotetrahydropyrimidin-l(22 / )-yl)-l-methyl- l / / -indazol-6-yl)ethyl)-4-fluoro-[l,4'-bipiperidin]-r-yl)pyridin-2-yl)amino)-A’,A'-dimethyl-7H- pyrrol o[2, 3 -<7]pyrimidine-6-carboxamide A557;7-cyclopentyl-2-((5-(4-(2-(3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)-l-methyl- l / / r-indazol-7-yl)ethyl)-4-fluoro-[l,4'-bipiperidin]-r-yl)pyridin-2-yl)amino)-Ar,AAdimethyl-7 / 7- pyrrolo[2,3-d]pyrimidine-6-carboxamide A558; or7-cyclopentyl-2-((5-(4-(2-(l-(3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)-l- methyl-177-indazol-6-yl)piperidin-4-yl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-jV,Ar-dimethyl- 7 / 7-pyrrolo[2,3-t(]pyrimidine-6-carboxamide A559; or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0267] In yet another embodiment, provided herein is a compound of:7-cyclopentyl-2-((4-((6-((2-(2,6-dioxopiperidin-3-yl)-l,3-dioxoisoindolin-4-yl)-amino)hexyl)carbamoyl)phenyl)amino)-A'r,Ar-dimethyl-777-pyrrolo[2,3-t7]pyrimidine-6- carboxamide A601:7-cyclopentyl-2-((4-((6-((2-(2,6-dioxopiperidin-3-yl)-l,3-dioxoisoindolin-4-yl)- amino)hexyl)(methyl)carbamoyl)phenyl)amino)-A7,Ar-dimethyl-7 / Z-pyrrolo[2,3-<7]pyrimidine-6- carboxamide A602; or7-cyclopentyl-2-((5-(4-((2-(2,6-dioxopiperidin-3-yl)-l,3-dioxoisoindolin-4-yl)- glycyl)piperazin-l-yl)pyridin-2-yl)amino)-jV,A / -dimethyl-7 / / -pyrrolo[2,3-J]pyrimidine-6- carboxamide A603; or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0268] In yet another embodiment, provided herein is a compound of:7-cyclopentyl-2-((5-(4-((2-(2,6-dioxopiperidin-3-yl)-l-oxoisoindolin-4-yl)- glycyl)piperazin-l-yl)pyridin-2-yl)amino)-jV,A''-dimethyl-7 / / -pyrrolo[2,3-J]pyrimidine-6- carboxamide A611;7-cyclopentyl-2-((4-((2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxoisoindolin-4-yl)piperidin-l-yl)ethyl)carbamoyl)phenyl)amino)-MALdimethyl-7 / 7-pyrrolo[2,3-t / ]pyrimidine- 6-carboxamide A612;7-cyclopentyl-2-((4-((4-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l -oxoisoindolin- 4-y l)piperi din- 1 -yl)butyl)carbamoyl)phenyl)amino)-A',Ar-dimethyl-7 / 7-pyrrolo[2, 3 -cfjpyrimidine- 6-carboxamide A613;7-cyclopentyl-2-((4-((6-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxoisoindolin- 4-yl)piperidin-l-yl)hexyl)carbamoyl)phenyl)amino)-Ar,A / -diraethyl-7Z / -pyrrolo[2,3-<i]pyrimidine- 6-carboxamide A614;7-cyclopentyl-2-((5-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxo- isoindolin-4-yl)piperidin-l-yl)acetyl)piperazin-l-yl)pyridin-2-yl)amino)-A7,Ar-dimethyl-7 / / - pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A615;7-cyclopentyl-2-((5-(4-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxo- isoindolin-4-yl)piperidin-l-yl)propanoyl)piperazin-l-yl)pyridin-2-yl)amino)-ArjV-dimethyl-7jE / - pyrrolo[2,3V|pyrimidine-6-carboxamide A616;7-cy clopentyl-2-((5 -(4-(4-(4-(2-(2, 6-dioxopiperidin-3 -yl)-6-fluoro- 1 -oxo- isoindolin-4-yl)piperidin-l-yl)butanoyl)piperazin-l-yl)pyridin-2-yl)amino)-7VuV-dimethyl-7 / / -pyrrol o[2, 3 -<7]pyrimidine-6-carboxamide A617;7-cyclopentyl-2-((4-((2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxoisoindolin-5-yl)piperidin-l-yl)ethyl)carbamoyl)phenyl)amino)-A’,AMimethyl-7H-pyrrolo[2,3-< / ]pyrimidine-6-carboxamide A618;7-cyclopentyl-2-((4-((4-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxoisoindolin-5-yl)piperidin-l-yl)butyl)carbamoyl)phenyl)amino)-JV,A / -dimethyl-7 / f-pyrrolo[2,3-<7]pyrimidine-6-carboxamide A619;7-cyclopentyl-2-((4-((6-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l -oxoisoindolin-5-yl)piperidin-l-yl)hexyl)carbamoyl)phenyl)amino)-A^V-dimethyl-7 / 7-pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A620;7-cyclopentyl-2-((5-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxo- isoindolin-5-yl)piperidin-l-yl)acetyl)piperazin-l-yl)pyridin-2-yl)amino)-7VjV-dimethyl-7 / / - pyrrolo[2,3-<7]pyrimidine-6-carboxamide A621;7-cyclopentyl-2-((5-(4-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxo- isoindolin-5-yl)piperidin-l-yl)propanoyl)piperazin-l-yl)pyridin-2-yl)amino)-jV / 7-dimethyl-7 / 7- pyrrolo[2,3-<7]pyrimidiiie-6-carboxamide A622; or7-cyclopentyl-2-((5-(4-(4-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxo- isoindolin-5-yl)piperidin-l-yl)butanoyl)piperazin-l-yl)pyridin-2-yl)amino)-A’,A-dimethyl-7 / 7- pyrrol o[2, 3 -tZ]pyrimidine-6-carboxamide A623; or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0269] In yet another embodiment, provided herein is a compound of:7-cyclopentyl-2-((4-((4-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4 / f- thieno[3,4-c]pyrrol-l-yl)methoxy)benzyl)carbamoyl)phenyl)amino)-Ar,A-dimethyl-7J / - pyrrolo[2,3-<7]pyrimidine-6-carboxamide A651;7-cyclopentyl-2-((4-((2-((4-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-42 / - thieno[3,4-c]pyrrol-l-yl)methoxy)benzyl)amino)ethyl)carbamoyl)phenyl)amino)- / V,7V-dimethyl- 7 / / -pyrrolo[2,3-< / |pyrimidine-6-carboxamide A652;7-cyclopentyl-2-((4-((4-((4-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4Ar- thieno[3,4-c]pyrrol-l-yl)methoxy)benzyl)amino)butyl)carbamoyl)phenyl)amino)-Ar,A7-dimethyl- 7 / 7-pyirolo[2,3-cf|pyrimidine-6-carboxamide A653; or7-cy cl opentyl-2-((4-((4-((5 -(2,6-di oxopi peri din-3 -y 1 )-4-oxo-5 , 6-dihy dro-477- thieno[3,4-c]pyrrol-l-yl)methoxy)benzyl)carbamoyl)phenyl)amino)-A,r,A-dimethyl-7 / A-pyrrolo- [2,3-<7]pyrimidine-6-carboxamide A654; or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0270] In yet another embodiment, provided herein is a compound of:3-(3-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)-2-oxoethoxy)phenyl)piperidine-2, 6-dione B101;3-(3-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / |- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)-3-oxopropoxy)phenyl)piperidine-2, 6-dione B102;A'r-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-£ / ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)-2-(3-(2,6-dioxopiperidin-3-yl)-2- methylphenoxy)acetamide B103;AL(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-tZ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)-2-(3-(2,6-dioxopiperidin-3-yl)-2- (tri fluorom ethy 1 )ph en oxy )acetam ide B 104 ;Az-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t / ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)-2-(3-(2,6-dioxopiperidin-3-yl)-4- methylphenoxy)acetamide Bl 05;AA(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-tZ|- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)-2-(3-(2,6-dioxopiperidin-3-yl)-4- (trifluoromethyl)phenoxy)acetamide B106;Ar-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)propyl)-2-(3-(2,6-dioxopiperidin-3-yl)-2- methylphenoxy)acetamide Bl 07;Az-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t7|- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)propyl)-2-(3-(2,6-dioxopiperidin-3-yl)-2- (trifluoromethyl)phenoxy)acetamide B108;AL(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]-pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)propyl)-2-(3-(2,6-dioxopiperidin-3-yl)-4- methylphenoxy)acetamide B109; orA’-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t / ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)propyl)-2-(3-(2,6-dioxopiperidin-3-yl)-4- (trifl uoromethyl)phenoxy)acetami de B 110 ; or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0271] In yet another embodiment, provided herein is a compound of:3-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)phenyl)piperidine-2, 6-dione Bill;3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)phenyl)piperidine-2, 6-dione Bl 12;3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethoxy)phenyl)piperidine-2, 6-dione Bl 13;3-(3-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-af]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)phenyl)piperidine-2, 6-dione B114;3-(3-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)phenyl)piperidine-2, 6-dione Bl 15;3-(3-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t / ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethoxy)phenyl)piperidine-2, 6-dione Bl 16;3-(4-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-tf|- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)propoxy)phenyl)piperidine-2, 6-dione B117;3-(3-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / |- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)propoxy)phenyl)piperidine-2, 6-dione Bl 18;3-(4-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-(7]- pyrimidin-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)piperi din- l-yl)phenyl)piperidine-2, 6-dione Bl 19;3-(4-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)methyl)piperi din- 1 -yl)phenyl)piperi dine- 2, 6-dione B120;3-(4-((4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)methyl)phenyl)piperidine- 2,6-dione B121;3-(3-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimi din-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperi din- l-yl)phenyl)piperidine-2, 6-dione B122;3-(3-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-] -yl)methyl)piperidin-l-yl)phenyl)piperidine- 2,6-dione B123;3-(3-((4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)methyl)phenyl)piperidine- 2,6-dione B124;3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- < / |pyrimidin-2-yl)amino)pyridin-3 -yl)piperazin- 1 -yl)ethyl)piperazin- 1 -yl)phenyl)piperidine-2, 6- dione B125;3-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3 -yl)piperazin- 1 -yl)ethyl)piperazin- 1 -yl)phenyl)piperidine-2, 6- dione B126;3-(4-(2-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)ethyl)phenyl)piperidine-2,6- di one B127; or3-(3-(2-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t(|pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)ethyl)phenyl)piperidine-2,6- dione B128; or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0272] In yet another embodiment, provided herein is a compound of:3-(4-((l -(2-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-J]pyrimidin-2-yl)aniino)piperidin-l-yl)sulfonyl)ethyl)piperidin-4- yl)oxy)phenyl)piperidine-2, 6-dione Bl 29;3-(3-((l-(2-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-< / ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)ethyl)piperidin-4-yl)oxy)phenyl)piperidine-2, 6-dione Bl 30;3-(4-((l-(3-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propyl)piperidin-4- yl)oxy)phenyl)piperidine-2, 6-dione B131;3-(4-(4-(2-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-tf]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)ethyl)piperazin-l- yl)phenyl)piperidine-2, 6-dione B132;3-(4-(4-(2-((4-((6-(difluoromethyl)-8-((17?,2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)ethyl)piperidin-l- yl)phenyl)piperidine-2, 6-dione B133;3-(4-(4-(3-((4-((6-(difluoromethyl)-8-((l / ?,27?)-2-hydroxy-2-methylcyclopentyi)- 7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propyl)piperazin- l-yl)phenyl)piperidine-2, 6-dione B134;3-(3-(4-(2-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-t7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)ethyl)piperazin-l- yl)phenyl)piperidine-2, 6-dione B135;3-(3-(4-(3-((4-((6-(difluoromethyl)-8-((17?,2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-i7]pyrimidin-2-yl)aniino)piperidin-l-yl)sulfonyl)propyl)piperazin- l-yl)phenyl)piperidine-2, 6-dione B136;3-(4-(3-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)-7- oxo-7,8-dihydropyrido[2,3-t7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propoxy)phenyl)- piperidine-2, 6-dione B137;3-(3-(3-((4-((6-(difluoromethyl)-8-((177,27?)-2-hydroxy-2-methylcyclopentyl)-7- oxo-7, 8-dihydropyrido[2,3-J]pyrimidin-2-yl)amino)piperidin-l-yi)sulfonyl)propoxy)phenyl)- piperidine-2, 6-dione B138;3 -(4-(4-(4-((4-((6-(difluoromethyl)-8-(( 17?, 27?)-2-hydroxy-2-methy I cyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-i7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)benzyl)piperazin- l-yl)phenyl)piperidine-2, 6-dione B139;3-(4-(4-(3-((4-((6-(diflUOromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-J]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)benzyl)piperazin- l-yl)phenyl)piperidine-2, 6-dione B140;3-(3-(4-(3-((4-((6-(difluoromethyl)-8-((17?,2J?)-2-hydroxy-2-methylcyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-tZ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)benzyl)piperazin-1 -yl)phenyl)piperi di ne-2, 6-dione B141;3-(3-(4-(4-((4-((6-(difluoromethyl)-8-((17?,2J?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-tf]pyrimidin-2-yl)amino)piperidin-l -yl)sulfonyl)benzyl)piperazin- l-yl)phenyl)piperidine-2, 6-dione B142;3-(4-((4-(4-((4-((6-(difluoromethyl)-8-((l / <2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-(7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenyl)piperazin- l-yl)methyl)phenyl)piperidine-2, 6-dione B143;3-(4-(4-((4-(4-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methyl- cyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)- phenyl)piperazin-l-yl)methyl)piperidin-l-yl)phenyl)piperidine-2, 6-dione B144;3-(4-((4-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)-7- oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)piperazin-l-yl)- methyl)phenyl)piperidine-2, 6-dione B145;3-(3-((4-((4-((6-(difluoromethyl)-8-((17?,21?)-2-hydroxy-2-methylcyclopentyl)-7- oxo-7,8-dihydropyrido[2,3-tf|pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)piperazin-l-yl)- methyl)phenyl)piperidine-2, 6-dione B146;3-(4-(4-((4-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)aniino)piperidin-l-yl)sulfonyl)piperazin-l-yl)- methyl)piperidin-l-yl)phenyl)piperidine-2, 6-dione B147;3-(4-(4-(3-((4-((6-(difluoromethyl)-8-((17?,2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-t(|pyrimidin-2-yl)amino)piperidin-l -yl)sulfonyl)propyl)piperazin- l-yl)phenyl)piperidine-2, 6-dione B148; or3-(3-((l-(3-((4-((6-(difluoromethyl)-8-((l / ^,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7, 8-dihy dropyrido[2, 3 -J]pyrimidin-2-yl)ami no)piperi din- 1 -y l)sulfonyl)propy I )pi peridin-4- yl)oxy)phenyl)piperidine-2, 6-dione B149; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0273] In yet another embodiment, provided herein is a compound of:3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZ]pyriniidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)phenyl)piperidine-2,6- di one Bl 50;3-(4-(2-(4-(4-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclo- pentyl)-7-oxo-7,8-dihydropyrido[2,3-<7]pyriniidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenyl)- piperazin- l-yl)ethyl)phenyl)piperidine-2, 6-dione B151;3-(4-(2-(4-(4-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclo- pentyl)-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenyl)- piperazin- l-yl)ethoxy)phenyl)piperidine-2, 6-dione B152;3-(4-(2-(4-(3-((4-((6-(difluoromethyl)-8-((17?,2 / ?)-2-hydroxy-2-methylcyclo- pentyl)-7-oxo-7,8-dihydropyrido[2,3-<f|pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenyl)- piperazin- 1 -yl)ethyl)phenyl)piperidine-2, 6-dione B 153;3-(3-(2-(4-((4-((6-(difluoromethyl)-8-((17?,2J?)-2-hydroxy-2-methylcyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-^pyrimidin-2-yl)amino)piperidin-l-yl)sulfbnyl)piperazin-l-yl)- ethoxy)phenyl)piperidine-2, 6-dione B154;3-(4-(3-(4-((4-((6-(difluoromethyl)-8-((lZ7,2JR)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-t / ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)piperazin-l-yl)- propoxy )phenyl)piperidine-2, 6-dione B155;3-(3-(3-(4-((4-((6-(difluoromethyl)-8-((l / ?,2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-<7]pyriniidin-2-yl)amino)piperidin-l-yl)sulfonyl)piperazin-l-yl)- propoxy )phenyl)piperidine-2, 6-dione Bl 56;3-(4-(4-(4-((4-((6-(difluoromethyl)-8-((17?,2JR)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-t(|pyrimidin-2-yl)amino)piperidin-l -yl)sulfonyl)phenethyl)- piperazin- l-yl)phenyl)piperidine-2, 6-dione B157;3-(4-(4-(2-(4-((4-((6-(difluoromethyl)-8-((17<27?)-2-hydroxy-2-methylcyclo- pentyl)-7-oxo-7,8-dihydropyrido[2,3-fi?]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenoxy)- ethyl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B158;3-(4-(4-(2-(3-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-nietliylcyclo- pentyl)-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenoxy)- ethyl)piperazin-l-yl)phenyl)piperidine-2, 6-dione Bl 59;3 -(3 -(( 1 -(3 -((4-((6-(difluoromethyl)-8-(( 1R, 27?)-2-hydroxy-2-m ethyl cyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenyl)piperidin- 4-yl)oxy)phenyl)piperidine-2, 6-dione B160;3-(4-((l -(3-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-tZ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenyl)piperidin- 4-yl)oxy)phenyl)piperidine-2, 6-dione B161;3-(4-((l-(4-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-< / ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenyl)piperidin- 4-yl)oxy)phenyl)piperidine-2, 6-dione Bl 62;3-(4-(4-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyriniidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)propyl)piperazin-l-yl)phenyl)piperidine- 2,6-dione B163;3-(4-(4-((4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)methyl)piperidin-l-yl)- phenyl)piperidine-2, 6-di one Bl 64;3-(4-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)-[l,4'-bipiperidin]-r-yl)phenyl)- piperidine-2, 6-dione B165;3-(4-(4-(l-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrinridin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-4-yl)piperazin-l-yl)- phenyl)piperidine-2, 6-dione B166;3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tf|pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)-[l,4'-bipiperidin]-r-yl)phenyl)- piperidine-2, 6-dione B167;3-(4-(4-(3-((4-((8-cyclopentyl-7-oxo-7,8-dihydropyrido[2,3-t7]pyrimidin-2-yi)- amino)piperi din- l-yl)sulfonyl)propyl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B168;3-(4-(4-(3-((4-((8-cyclopentyl-6-(difluoromethyl)-7-oxo-7,8-dihydropyrido[2,3- J]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propyl)piperazin-l-yl)phenyl)piperidine-2,6- dione B169;3-(4-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2,6- dione B170;3-(4-(4-((3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [23 -^pyrimi din-2 -yl)amino)pyri din-3 -yl)piperazin-l-yl)piperidin-l-yl)methyl)piperi din- 1-yl)- phenyl)piperidine-2, 6-dione Bl 71;3-(4-((5)-2-((4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-^]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l -yl)piperidin-l-yl)methyl)- morpholino)phenyl)piperidine-2, 6-dione B172;3-(4-(( / ?)-2-((4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-tZ]pyrimidin-2-yl)aniino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)methyl)- morpholino)phenyl)piperidine-2, 6-dione B173;3-(4-((4-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-cZ]pyrimidin-2-yl)aniino)pyridin-3-yl)piperazin-l-yl)cyclohexyl)piperidin-l-yl)methyl)- phenyl)piperidine-2, 6-dione Bl 74;3-(4-(2-(4-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)cyclohexyl)piperidin-l-yl)ethy])- phenyl)piperidine-2, 6-dione Bl 75;3-(4-(3-((4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<Z]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l -yl)methyl)azetidin-l-yl)- phenyl)piperidine-2, 6-dione B176;3-(4-(4-((5)-2-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-<7]pyriniidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)niethyl)morpholino)piperidin-l- yl)phenyl)piperidine-2, 6-dione B177;3-(4-(4-((J?)-2-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-tZ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l -yl)methyl)morpholino)piperidin-l- yl)phenyl)piperidine-2, 6-dione B178;3-(4-(4-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-tZ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)cyclohexyl)piperazin-l-yl)- phenyl)piperidine-2, 6-dione B179;3-(4-(4-(2-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)ethyl)piperazin-l-yl)- phenyl)piperidine-2, 6-dione Bl 80;3-(4-(2-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3"t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)cyclohexyl)ethyl)phenyl)piperidine-2,6- dione B181;3-(4-(4-(3-(4-(6-((6-Acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- d / pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)cyclohexyl)piperazin-l-yl)phenyl)- piperidine-2, 6-dione B182;3-(4-(4-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-] -yl)propyl)piperidin-l-yl)phenyl)piperidine-2,6- di one Bl 83;3-(4-(3-(4-(4-(6-((6-acetyi-8-cyclopentyl-5-methyi-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)propoxy)phenyl)piperidine- 2,6-dione B184;3-(4-(r-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)-[4,4'-bipiperidin]-l-yl)phenyl)- piperidine-2, 6-dione B185;3-(4-(4-((3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-< / |pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)azetidin-l-yl)methyl)piperidin-l-yl)- phenyl)piperidine-2, 6-dione Bl 86;3-(4-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / |- pyrimidin-2yl)amino)pyridin-3-yl)piperazin-l-yl)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2,6- dione B187;3-(4-(4-(r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tf|pyrimidin-2-yl)aniino)pyridin-3-yl)-[l,4'-bipiperidin]-4-yl)piperazin-l-yl)phenyl)piperidine- 2,6-dione B188;3-(4-(4-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)cyclohexyl)piperazin-l-yl)phenyl)- piperidine-2, 6-dione B189;3-(4-(4-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- ^pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)cyclohexyl)piperidin-l-yl)phenyl)- piperidine-2, 6-dione B190;3-(3-(2-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)aniino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)ethoxy)phenyl)piperidine-2,6-dione B191;3-(3-(3-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2 -yl)amino)pyridin-3-yl)piperazin-l-yl)piperi din-1 -yl)propoxy)phenyl)piperidine-2, 6-dione B192;3-(4-(4-(l-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)piperazin-l-yl)phenyl)piperidine-2,6-dione B193;3-(4-(4-(4-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3 -yl)methyl)piperazin-l-yl)piperi din- l-yl)phenyl)piperi dine-2,6-dione B194;3-(4-(r-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / |- yrimidin-2-yl)amino)pyridin-3-yl)methyl)-[4,4'-bipiperidin]-l-yl)phenyl)piperidine-2, 6-dione B195;3-(4-(4-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]- pyrimidin-2-yl)amino)pyridin-3-yl)methyl)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2, 6-dione B196;3-(4-(4-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]- pyrimidin-2-yl)amino)pyridin-3-yl)oxy)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2, 6-dione B197;3-(4-(4-(2-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]- pyrimidin-2-yl)amino)pyridin-3-yl)ethyl)-[l,4'-bipiperidin]-l '-yl)phenyl)piperidine-2, 6-dione B198;3-(4-(4-(((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]- pyrimidin-2-yl)amino)pyridin-3-yl)oxy)methyl)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2,6- dione B199;3-(4-(4-(4-(2-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)ethyl)piperazin-l-yl)piperidin-l-yl)phenyl)piperidine-2,6- dione B200;3-(4-(4-(l-(2-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / jpyrimidin-2-yl)amino)pyridin-3-yl)ethyl)piperidin-4-yl)piperazin-l-yl)phenyl)piperidine-2,6- di one B201;3-(4-(r-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZ]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)-[4,4'-bipiperidin]-l-yl)phenyl)piperidine-2,6- di one B202;3-(4-(4-(l-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<y]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)piperidin-4-yl)piperazin-l-yl)phenyl)- piperidine-2, 6-dione B203;3-(4-(4-(4-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)piperazin-l-yl)piperidin-l-yl)phenyl)- piperidine-2, 6-dione B204;3-(4-(4-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2,6- di one B205;3-(4-(r-(3-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J]pyrimidin-2-yl)amino)pyridin-3-yl)propyl)-[4,4'-bipiperidin]-l-yl)phenyl)piperidine-2,6-dione B206;3-(4-(4-(l-(3-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)propyl)piperidin-4-yl)piperazin-l-yl)phenyl)piperidine-2,6- dione B207;3-(4-(4-(4-(3-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- c / ]pyrimidin-2-yl)amino)pyridin-3-yl)propyl)piperazin-l-yl)piperidin-l-yl)phenyl)piperidine-2,6- di one B208;3-(4-(4-(3-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J]- pyrimidin-2-yl)amino)pyridin-3-yl)propyl)-[l,4’-bipiperidin]-r-yl)phenyl)piperidine-2,6-dione B209;3-(3-(4-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperazin-l-yl)phenyl)piperidine- 2,6-dione B210;3-(4-(4-(((5)-4-(6-((6-aCetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3 -<7]pyrimidin-2-yl)amino)pyri din-3 -yl)morpholin-2-yl)methyl)piperazin-l-yl)phenyl)- piperidine-2, 6-dione B211;3-(4-(4-(((7?)-4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido-[2,3-tf]pyrimidin-2-yl)amino)pyridin-3-yl)morpholin-2-yl)methyl)piperazin-l-yl)phenyl)- piperidine-2, 6-dione B212;3-(3-(4-(((5)-4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)morpholin-2-yl)methyl)piperazin-l-yl)phenyl)- piperidine-2, 6-dione B213;3-(4-(2-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)ethyl)phenyl)piperidine-2,6- dione B214;3-(4-(2-(r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)-[l,4'-bipiperidin]-4-yl)ethyl)phenyl)piperidine-2,6-dione B215;3-(4-((5)-2-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido-[2,3 -<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)morpholino)phenyl)piperi dine- 2,6-dione B216;3-(4-((7?)-2-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido-[2,3 -d]pyrimidin-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)methyl)morpholino)phenyl)piperidine- 2,6-dione B217;3-(4-(3-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J|- pyrimidin-2-yl)amino)pyridin-3-yl)oxy)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2, 6-dione B218;3-(4-(4-(l-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t7]pyrimidin-2-yl)amino)pyridin-3 -yl)methyl)piperi din-3 -yl)piperazin-l-yl)phenyl)piperi dine- 2,6-dione B219;3-(3-(4-(l-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimi din-2-yl)amino)pyri din-3 -yl)methyl)piperi din-3 -yl)piperazin-l-yl)phenyl)piperidine- 2,6-dione B220;3-(4-(4-(l-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-t / ]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)piperidin-3-yl)piperazin-l-yl)phenyi)- piperidine-2, 6-dione B221;3-(3-(4-(l-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido-[2,3 -<f|pyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)piperi din-3 -yi)piperazin-l-yl)phenyl)-piperidine-2, 6-dione B222;3-(3-(4-(l-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-c / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperidin-4-yl)piperazin-l-yl)- phenyl)piperidine-2, 6-dione B223;3-(4-(4-(l-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-t7]pyrimidin-2-yl)amino)pyri din-3 -yl)piperidin-4-yl)methyl)piperidin-4-yl)piperazin-l-yl)- phenyl)piperidine-2, 6-dione B224;3-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)ammo)pyridin-3 -yl)piperidin-4-yl)piperazin- 1 -yl)phenyl)piperidine-2, 6-dione B225;3-(4-(4-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)azetidin-3-yl)methyl)piperazin-l-yl)phenyl)piperidine-2,6- dione B226;3-(4-(4-(2-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)ethyl)piperazin-l-yl)phenyl)piperidine-2,6- di one B227;3-(4-(3-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- Jjpyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)azetidin-l-yl)phenyl)piperidine-2,6- dione B228;3-(4-(2-(2-(4-(6-((6-acetyl-8-cyclopentyi-5-methyl-7-oxo-7,8-dihydropyrido[2,3~ d]pyriinidin-2-yl)amino)pyridin-3-yl)piperazin-1 -yl)ethyl)-2,7-diazaspiro[3.5]nonan-7- yl)phenyl)piperidine-2, 6-dione B229;3-(4-(4-(3-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- c / ]pyrimidin-2 -yl)amino)pyri din-3 -yl)oxy)propyl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B230;3-(4-(l-(3-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- J]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)propyl)piperidin-4-yl)phenyl)piperidine-2, 6-dione B231;3-(3-(4-(3-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t7jpyrimidin-2-yl)amino)pyridin-3-yl)oxy)propyl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B232;3-(3-(l-(3-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZ]pyriniidin-2-yl)amino)pyridin-3-yl)oxy)propyl)piperidin-4-yl)phenyl)piperidine-2, 6-dione B233;3-(4-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t / ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)propoxy)phenyl)piperidine-2, 6-dione B234;3-(4-(4-(3-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)propyl)piperidin-l-yl)phenyl)piperidine-2, 6-dione B235;3-(3-(4-(3-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- J]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)propyl)piperidin-l-yl)phenyl)piperidine-2, 6-dione B236;3-(4-(3-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)propoxy)phenyl)piperidine-2, 6-dione B237;3-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-tfl- pyrimidin-2-yl)amino)pyridin-3-yl)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2, 6-dione B238;3-(4-(r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-(7]~ pyrimidin-2-yl)amino)pyridin-3-yl)-[4,4'-bipiperidin]-l-yl)phenyl)piperidine-2, 6-dione B239;3-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-^- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B240;3-(4-(l'-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t / j- pyrimidin-2-yl)amino)pyridin-3-yl)-[l,4'-bipiperidin]-4-yl)phenyl)piperidine-2, 6-dione B241;3-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2, 6-dione B242;3-(3-(r-(6-((6-acetyl"8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J]- pyrimidin-2-yl)amino)pyridin-3-yl)-[4,4'-bipiperidin]-l-yl)phenyl)piperidine-2, 6-dione B243;3-(3-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B244;3-(3-(l'-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t / j- pyrimidin-2-yl)amino)pyridin-3-yl)-[l,4'-bipiperidin]-4-yl)phenyl)piperidine-2, 6-dione B245;3-(4-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)methyl)piperidin-l-yl)phenyl)piperidine-2,6- di one B246;3-(4-(4-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperazin-l-yl)phenyl)piperidine- 2,6-dione B247;3-(4-(l-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperidin-4-yl)phenyl)piperidine-2,6- dione B248;3-(3-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)methyl)piperidin-l-yl)phenyl)piperidine-2,6- di one B249;3-(3-(l-((l-(6-((6-acetyl-8-cyclopentyI-5-methyl-7-oxo-7,8-dihydropyrido[2,3-Jjpyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperidin-4-yl)phenyl)piperidine-2,6- dione B250;3-(3-(4-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperidin-l-yl)phenyl)piperidine-2,6- dione B251;3-(4-(lX(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]- pyrimidin-2-yl)amino)pyridin-3-yl)methyl)-[l,4'-bipiperidin]-4-yl)phenyl)piperidine-2, 6-dione B252;3-(4-(l-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / jpyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-4-yl)phenyl)piperidine-2,6- dione B253;3-(4-(l-(2-(4-(6-((6-acetyl-8-cyclopentyi-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)ethyl)piperidin-4-yl)phenyl)piperidine-2,6- dione B254;3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)ethyl)piperazin-l-yl)phenyl)piperidine-2,6- dione B255;3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)ethyl)piperidin-l-yl)phenyl)piperidine-2,6- dione B256;3-(3-(l -(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- < / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-4-yl)phenyl)piperidine-2,6- di one B257;3-(3-(l-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)ainino)pyridin-3-yl)piperidin-l-yl)ethyl)piperidin-4-yl)phenyl)piperidine-2,6- di one B258;3-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)ethyl)piperazin-l -yl)phenyl)piperidine-2,6- dione B259;3-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)ethyl)piperidin-l-yl)phenyl)piperidine-2,6- dione B260;3-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- ef|pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)phenyl)piperidine-2,6- di one B261;3-(4-(2-(r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]- pyrimidin-2-yl)amino)pyridin-3-yI)-[4,4'-bipiperidin]-l -yl)ethyl)phenyl)piperidine-2, 6-dione B262;3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / |- pyrimidin-2-yl)amino)pyridin-3-yl)-[l,4'-bipiperidin]-r-yl)ethyl)phenyl)piperidine-2, 6-dione B263;3-(3-(4-(4-(2-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- < / |pyrimidin-2-yl)amino)pyridin-3-yl)ethyl)piperazin-l-yl)piperidin-l-yl)phenyl)piperidine-2,6- dione B264;3-(3-(4-(2-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)ethyl)-[l ,4'-bipiperidin]-r-yl)phenyl)piperidine-2, 6-dione B265;3-(3-(4-(((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7J- pyrimidin-2-yl)amino)pyridin-3-yl)oxy)methyl)-[l,4'-bipiperidin]-l'-yl)phenyl)piperidine-2,6-dione B266;3-(3-(r-(2-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)ethyl)-[4,4'-bipiperidin]-l-yl)phenyl)piperidine-2, 6-dione B267;3-(3-(4-(l-(2-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)ethyl)piperidin-4-yl)piperazin-l-yl)phenyl)piperidine-2,6- di one B268;3-(3-(4-(l-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-t7]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)piperidin-4-yl)piperazin-l-yl)phenyl)- piperidine-2, 6-dione B269;3-(3-(4-(4-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)aniino)pyridin-3-yl)oxy)ethyl)piperazin-l-yl)piperidin-l-yl)phenyl)- piperidine-2, 6-dione B270;3-(4-(l'-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)-[l,4'-bipiperidin]-4-yl)phenyl)piperidine-2,6- dione B271,3-(4-(4-(2-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- Jjpyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)ethyl)piperidin-l-yl)phenyl)piperidine-2,6- dione B272;(1S)-3-(4-(4-(((5T)-4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-Jjpyrimidin-2-yl)amino)pyridin-3-yl)morpholin-2-yl)methyl)piperazin-l-yl)phenyl)- 3-methylpiperidine-2, 6-dione B273;3-(4-(l-(2-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)ethyl)piperidin-4-yl)phenyl)piperidine-2,6- dione B274;3-(4-((r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J]- pyrimidin-2-yl)amino)pyridin-3-yl)-[l,4'-bipiperidin]-4-yl)methyl)phenyl)piperidine-2, 6-dione B275;3-(4-(4-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3"t7]- pyrimidin-2-yl)amino)pyri din-3 -yl)oxy)ethyl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B276;3-(4-(4-(2-((6-((6-acetyl-8-cyclopentyl-5-niethyl-7-oxo-7,8-dihydropyrido[2,3-<7|-pyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)piperidin-l -yl)phenyl)piperidine-2, 6-dione B277;3-(4-(2-(r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoro-[l,4'-bipiperidin]-4-yl)ethyl)phenyl)piperidine- 2,6-dione B278;3-(3-(3-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)azetidin-l-yl)phenyl)piperidine-2,6- di one B279;3-(4-(2-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3 -yl)piperazin- 1 -y l)piperi din- 1 -yl)- 1 , 1 -difluoroethyl)phenyl)- piperidine-2, 6-dione B280;3-(3-(2-(4-(4-(6-((6-acetyl-8-cyclopentyi-5-methyl-7-oxo-7,8-dihydropyrido[2,3- d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin- 1 -yl)piperidin- 1 -yl)- 1 , 1 -difluoroethyl)phenyl)- piperidine-2, 6-dione B281;3-(4-(2-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyri din-3 -yl)piperazin- 1 -yl)azetidin- 1 -y 1 ) - 1 , 1 -difluoroethyl)phenyl)- piperidine-2, 6-dione B282;3-(3-(2-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- Jjpyrimidin-2-yl)amino)pyridin-3 -yl)piperazin- 1 -yl)azetidin- 1 -yl)- 1 , 1 -difluoroethyl)phenyl)- piperidine-2, 6-dione B283;3-(4-((3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- d]pyriinidin-2-yl)amino)pyridin-3-yl)piperazin-1 -yl)azetidin-1 -yl)methyl)phenyl)piperidine-2,6- dione B284;3-(3-((3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- cZ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)azetidin-l-yl)methyl)phenyl)piperidine-2,6- dione B285;3-(3-(2-(r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- J]pyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoro-[l,4'-bipiperidin]-4-yl)ethyl)phenyl)piperidine- 2,6-dione B286;3-(4-((r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3V|- pyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoro-[l,4'-bipiperidin]-4-yl)methyl)phenyl)piperidine- 2,6-dione B287;3-(3-((r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-i / ]- pyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoro-[l,4'-bipiperidin]-4-yl)methyl)phenyl)piperidine- 2,6-dione B288;3-(4-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- J]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fliioroazetidin-3-yl)ethyl)phenyl)- piperidine-2, 6-dione B289;3-(3-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazetidin-3-yl)ethyl)phenyl)- piperidine-2, 6-dione B290;3-(4-((l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyri din-3 -yl)piperidin-4-y l)-3 -fluoroazetidin-3 -yl)methyl)phenyl)- piperidine-2, 6-dione B291;3-(3-((l-(l-(6-((6-acetyl-8-cyclopentyI-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazetidin-3-yl)methyl)phenyl)- piperidine-2, 6-dione B292;3-(4-(l-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoropiperidin-4-yl)methyl)azetidin-3-yl)phenyl)- piperidine-2, 6-dione B293;3-(3-(l-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- c / ]pyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoropiperidin-4-yl)methyl)azetidin-3-yl)phenyl)- piperidine-2, 6-dione B294;3-(4-(2-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / jpyrimidin-2-yl)amino)pyri din-3 -yl)azeti din-3 -yl)piperazin-l-yl)ethyl)phenyl)piperidine-2, 6- dione B295;3-(3-(2-(4-(l-(6-((6-acetyl-8-cyclopentyi-5-methyl-7-<)xo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)azetidin-3-yl)piperazin-l-yl)ethyl)phenyl)piperidine-2,6- dione B296;3-(4-((4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)azetidin-3-yl)piperazin-l-yl)methyl)phenyl)piperidine-2,6- di one B297;3-(3-((4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3<i]pyrimidin-2-yl)amino)pyridin-3-yl)azetidin-3-yl)piperazin-l -yl)methyl)phenyl)piperidine-2,6- dione B298;3-(3-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- d]pyrimidin-2-yl)amino)pyridin-3-yl)azetidin-3-yl)piperidin-4-yl)ethyl)phenyl)piperidine-2,6- dione B299;3-(3-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)ainino)pyridin-3-yl)azetidin-3-yl)-4-fluoropiperidin-4-yl)ethyl)phenyl)- piperidine-2, 6-dione B300;3-(3-(8-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)-3-azabicyclo[3.2.1]octan-3-yi)- phenyl)piperidine-2, 6-dione B301;3-(3-(3-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)-8-azabicyclo[3.2.1]octan-8-yl)- phenyl)piperidine-2, 6-di one B302;3-(3-(4-((3-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-l-yl)- phenyl)piperidine-2, 6-dione B303;3-(3-(4-((8-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZ]pyrimidin-2-yl)amino)pyridin-3-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-l-yl)- phenyl)piperidine-2, 6-dione B304;3-(3-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)methyl)-4-fluoropiperidin-l-yl)phenyl)- piperidine-2, 6-dione B305;3-(4-(4-((4-(6-((6-acetyl-8-cyClOpentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)methyl)-4-fluoropiperidin-l-yl)phenyl)- piperidine-2, 6-dione B306;(S)-3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-tf]pyrinridin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)phenyl)-3-m ethyl- piperidine-2, 6-dione B307;(7?)-3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yi)phenyi)-3-methyi-piperidine-2, 6-dione B308;(S)-3-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-c / jpyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l -yl)phenyl)-3-m ethyl- piperidine-2, 6-dione B309;(7?)-3-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3 -d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)phenyl)-3 -methyl- piperidine-2, 6-dione B310;3-(4-(l -((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t(jpyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoropiperidin-4-yl)methyl)piperidin-4-yl)phenyl)- piperidine-2, 6-dione B311;3-(3-(l-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoropiperidin-4-yl)methyl)piperidin-4-yl)phenyl)- piperidine-2, 6-dione B312;3-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-fluorophenyl)piperidine-2,6- dione B313;3-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-3-fluorophenyl)piperidine-2,6- dione B314;3-(4-(4-(l-(6-((6-aCetyl-8-cyClOpentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-chlorophenyl)piperidine-2,6- dione B315;3-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-tf|- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-3-chlorophenyl)piperidine-2,6- dione B316;3-(4-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-i / ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)azetidin-l-yl)phenyl)piperidine-2, 6-dione B317;3-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / jpyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l -yl)ethyl)piperidin-l-yl)-5-f]uorophenyl)- piperidine-2, 6-dione B318;3-(5-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZ]pyriniidin-2-yl)amino)pyridin-3 -yl)piperazin-l-yl)ethyl)piperi din- l-yl)-2 -fluorophenyl)- piperidine-2, 6-dione B319;3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / jpyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-3-fluorophenyl)- piperidine-2, 6-dione B320;3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-2-fluorophenyl)- piperidine-2, 6-dione B321;3-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)ethyl)piperi din- 1-y l)-2-fluorophenyl)- piperidine-2, 6-dione B322;3-(3-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)-4-fluoropiperidin-l-yl)phenyl)- piperidine-2, 6-dione B323; or3-(4-(4-(4-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido-[2,3 V|pyrimi din-2-yl)amino)pyri din-3 -yl)oxy)ethyl)piperazin- 1 -yl)piperi din- 1 -yi)phenyl)- piperidine-2, 6-dione B324; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0274] In yet another embodiment, provided herein is a compound of:3-(4-(2-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)-7- oxo-7, 8-dihydropyrido[2,3-J]pyrimidin-2-yl)amino)piperi din- 1 -yl)sulfonyl)ethoxy)phenyl)- piperidine-2, 6-dione B351;3-(4-(4-(((4-((6-(difluoromethyl)-8-((17?,21?)-2-hydroxy-2-methylcyclopentyl)-7- oxo-7, 8-dihydropyrido[2, 3-t / ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)methyl)piperidin-l- yl)phenyl)piperidine-2, 6-dione B352;3-(3-(2-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)-7- oxo-7, 8-dihydropyrido[2,3-J]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)ethoxy)phenyl)- piperidine-2, 6-dione B353;3-(4-(4-(((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)-7- oxo-7, 8-dihydropyrido[2,3-t(]pyrimi din-2 -yl)amino)piperidin-l-yl)sulfonyl)methyl)-[l, 4'- bipiperi din]- r-yl)phenyl)piperidine-2, 6-dione B354;3-(4-(4-(l-(2-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methyl- cyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)- ethyl)piperidin-4-yl)piperazin- 1 -yl)phenyl)piperidine-2, 6-dione B355;3-(4-((4-(3-((4-((6-(difluoromethyl)-8-((l / <2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-t / ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenyl)piperazin- 1 -yl)methyl)phenyl)piperidine-2, 6-dione B356;3-(4-(4-((4-(3-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methyl- cyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)- phenyl)piperazin-l-yl)methyl)piperidin-l-yl)phenyl)piperidine-2, 6-dione B357;4-(3-(4-((4-(3-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methyl- cyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-fl?]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)- phenyl)piperazin-l-yl)methyl)piperidin-l-yl)phenyl)piperidine-2, 6-dione B358;3-(4-(2-(4-((4-((6-(difluoromethyl)-8-((lZ^,2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-t / ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)piperazin-l-yl)- ethyl)phenyl)piperidine-2, 6-dione B359;3-(4-(4-(4-((4-((6-(difluoromethyl)-8-((17?,2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)aniino)piperidin-l-yl)sulfonyl)piperazin-l-yl)- piperidin-l-yl)phenyl)piperidine-2, 6-dione B360;3-(3-((l-(3-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-t7jpyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propyl)piperidin-4- yl)oxy)phenyl)-3-methylpiperidine-2, 6-dione B361; or3-(4-((l-(3-((4-((6-(difluoromethyl)-8-((l / ^,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7, 8-dihy dropyrido[2, 3 -J]pyrimidin-2-yl)ami no)piperi din- 1 -y l)sulfonyl)propy I )pi peridin-4- yl)oxy)phenyl)-3-methylpiperidine-2, 6-dione B362; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0275] In yet another embodiment, provided herein is a compound of:3-(3-(4-((3-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- eZ]pyrimidin-2-yl)amino)pyridin-3-yl)azetidin-l-yl)methyl)-4-fluoropiperidin-l-yl)phenyl)- piperidine-2, 6-dione B363;3-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t / ]- pyrimidin-2-yl)amino)pyridin-3-yl)azetidin-3-yl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B364;3-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-4-fluorophenyl)- piperidine-2, 6-dione B365;3-(3-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyri din-3 -yl)piperidin-l -yl)methyl)-4-fluoropiperidin- l-yl)phenyl)-3- methylpiperidine-2, 6-dione B366;(S)-3-(3-(4-((4-(6-((6-acetyI-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)methyl)-4-fluoropiperidm-l-yl)phenyl)- 3 -methylpiperidine-2, 6-dione B367;(5)-3-(4-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<Z]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazetidin-3-yl)ethyl)phenyl)-3- methylpiperidine-2, 6-dione B368;(7?)-3-(4-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-< / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazetidin-3-yl)ethyl)phenyl)-3- methylpiperidine-2, 6-dione B369;3-(4-(7-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl)phenyl)- piperidine-2, 6-dione B370;( / ^)-3-(4-((7?)-2-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)morpholino)phenyl)-3- methylpiperidine-2, 6-dione B371;(5)-3-(4-((7?)-2-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-tf|pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)morpholino)phenyl)-3- methylpiperidine-2, 6-dione B372;(A)-3-(4-((7?)-2-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)methyl)morpholino)phenyl)-3- methylpiperidine-2, 6-dione B373;(LS)-3-(4-((7?)-2-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)methyl)morpholino)phenyl)-3- methylpiperidine-2, 6-dione B374; or(7?)-3-(4-(4-(((5)-4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-< / |pyrimidin-2-yl)amino)pyridin-3-yl)morpholin-2-yl)methyl)piperazin-l-yl)phenyl)- 3 -methylpiperidine-2, 6-dione B375; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0276] In yet another embodiment, provided herein is l-(4-((l-(3-((4-((6-(difhioro- methyl)-8-((l / ?,27?)-2-hydroxy-2-methylcyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-t7]pyrimidin- 2-yl)amino)piperidin-l-yl)sulfonyl)propyl)piperidin-4-yl)oxy)phenyl)dihydropyrimidine- 2,4(17 / ,3 / / )-dione B401; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0277] In yet another embodiment, provided herein is a compound of: l-(4-(4-(3-((4-((6-(difluoromethyl)-8-((17?,2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-< / ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propyl)piperazin- l-yl)phenyl)dihydropyrimidine-2, 4(177, 37 / )-dione B402; l-(2-chloro-4-(4-(3-((4-((6-(difluoromethyl)-8-((l / ?,2 / ?)-2-hydroxy-2-methyl- cyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)- propyi)piperazin-l-yl)phenyl)dihydropyrimidine-2,4(177,37 / )-dione B403; l-(4-(4-(3-((4-((6-(difluoromethyl)-8-((l / ?,2 / / )-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propyl)piperazin- l-yl)-2-fluorophenyl)dihydropyrimidine-2, 4(1 / 7, 37 / )-dione B404; l-(4-(4-(3-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-tZ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propyl)piperazin- l-yl)-2-methylphenyl)dihydropyrimidine-2, 4(1 / 7, 37 / )-dione B405;l-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZ]pyrimidin-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)ethyl)piperi din- l-yl)phenyl)dihydro- pyrimidine-2, 4(177, 377)-dione B406; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t / ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)phenyl)dihydropyrimidine- 2,4(177,377)-dione B407; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-fluorophenyl)dihydro- pyrimidine-2, 4(177, 377)-dione B408; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-chlorophenyl)dihydro- pyrimidine-2, 4(177, 377)-dione B409; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-(trifluoromethyl)phenyl)- dihydropyrimidine-2, 4(177, 377)-dione B410; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-methylphenyl)dihydro- pyrimidine-2, 4(177, 377)-dione B411; l-(4-(4-(l-(6-((6-acetyl-8-cyclOpentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-(7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2,3-dimethylphenyl)dihydro- pyrimidine-2, 4(177, 37 / )-dione B412; l-(5-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / jpyrimidin-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)ethyl)piperi din- l-yl)-2,4-dimethylphenyl)- dihydropyrimidine-2, 4(177, 377)-dione B413; l-(5-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-<)xo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)ethyl)piperi din- l-yl)-2-chloro-3 -methyl- phenyl)dihydropyrimidine-2, 4(177, 377)-dione B414; l-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-5-chloro-2-methyl- phenyl)dihydropyrimidine-2,4(177,377)-dione B415; or l-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperazin-l -yl)phenyl)dihydro- pyrimidine-2, 4(1 / 7, 3 / / )-dione B416; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0278] In yet another embodiment, provided herein is a compound of: l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7|- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-chloro-5-methylphenyl)- dihydropyrimidine-2, 4(177, 37 / )-dione JB451; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-7|- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-fluoro-3-methylphenyl)- dihydropyrimidine-2,4(l / f,3 / / )-dione B452; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7|- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-fluoro-5-methylphenyl)- dihydropyrimidine-2,4(17 / ,3 / / )-dione B453; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-chloro-6-methylphenyl)- dihydropyrimidine-2, 4(177, 377)-dione B454; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-7|- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-3-fluoro-2-methylphenyl)- dihydropyrimidine-2,4(l / Z,3ZZ)-dione B455; l-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)phenyl)dihydro- pyrimidine-2,4(17 / ,37Q-dione B456; l-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZ]pyrimidin-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)ethyl)piperi din- l-yl)-2-chlorophenyl)- dihydropyrimidine-2, 4(177, 377)-dione B457; l-(5-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-7]pyrimidin-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)ethyl)piperi din- l-yl)-2-chlorophenyl)- dihydropyrimidine-2,4(l#,377)-dione B458; l-(5-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l -yl)-2-fluorophenyl)- dihydropyrimidine-2, 4( 1 Z / ,3 / / )-dione B459; l-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t7]pyrimidin-2-yl)amino)pyridin-3 -yl)piperazin- 1 -yl)ethyl)piperidin- 1 -yl)-2-fluorophenyl)- dihydropyrimidine-2,4(l / 7,3 / / )-dione B460; l-(5-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l -yl)ethyl)piperidin-l-yl)-2-methylphenyl)- dihydropyrimidine-2, 4(1 / 7, 3 / 7)-dione B461; l-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l -yl)-2-methylphenyl)- dihydropyrimidine-2, 4(1 / 7, 3 / / )-dione B462; l-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-2-chloro-6-methyl- phenyl)dihydropyrimidine-2, 4(1 / 7, 3 / / )-dione B463; l-(5-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-4-chloro-2-methyl- phenyl)dihydropyrimidine-2, 4(1 / 7, 3 / / )-dione B464; l-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-2-chloro-4-methyl- phenyl)dihydropyrimidine-2,4( l / / ,3 / / )-dione B465; l-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t7]pyrimidin-2-yl)aniino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-4-chloro-2-methyl- phenyl)dihydropyrimidine-2, 4(1 / 7, 3 / / )-dione B466; l-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)ethyl)piperi din- l-yl)-2-chlorophenyl)- dihydropyrimidine-2, 4(1 / 7, 3 / 7)-di one B467; l-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperazin-l-yl)-2-chlorophenyl)- dihydropyrimidine-2,4(l / 7,3 / / )-dione B468; l-(4-(4-(2-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / |pyrimidin-2-yl)aniino)pyridin-3 -yl)piperidin-4-yl)ethyl)piperazin- 1 -yl)phenyl)dihydro-pyrimidine-2, 4(177, 377)-dione B469; l-(3-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)piperidin-l-yl)phenyl)dihydro- pyrimidine-2, 4(177, 377)-dione B470; l-(3-(4-((3-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-l-yl)- phenyl)dihydropyrimidine-2,4(l / 7,377)-dione B471; or l-(4-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t7jpyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazeti din-3 -yl)ethyl)-2-chloro- phenyl)dihydropyrimidine-2,4(177,377)-dione B472; or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0279] In yet another embodiment, provided herein is 3-(6-(2-(4-(6-((6-acetyl-8- cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-(7]-pyrimidin-2-yl)amino)pyridin-3- yl)piperazin-l-yl)-2-oxoethoxy)-l-methyl-177-indazol-3-yl)-piperidine-2, 6-dione B501; or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof, or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0280] In yet another embodiment, provided herein is 3-(7-(2-(4-(3-((4-((6-(difluoro- methyl)-8-((17?,25)-2-hydroxy-2-methylcyclo-pentyl)-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperi din- 1 -yl)sulfonyl)propyl)-piperazin- 1 -yl)-2-oxoethoxy)-l -methyl- 177-indazol-3 -yl)piperidine-2, 6-dione B502; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0281] In yet another embodiment, provided herein is 3-(6-(4-(l-(6-((6-acetyl-8-cyclo- pentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]-pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4- yl)piperazin-l-yl)-l-methyl-177-indazol-3-yl)-piperidine-2, 6-dione B503; or 3-(6-(2-(l-(l-(6-((6- acetyi-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)pyridin-3- yl)piperidin-4-yl)-3-fluoroazetidin-3-yl)ethyl)-l-methyl-177-indazol-3-yl)piperidine-2, 6-dioneB504; or a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

[0282] In yet another embodiment, provided herein is:3-(7-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-l-methyl-17 / -indazol-3-yl)-3- methylpiperidine-2, 6-dione B505;3-(7-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- < / |pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazetidin-3-yl)ethyl)-l-methyl-lJcf- indazol-3-yl)piperidine-2, 6-dione B506;3-(6-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / |- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)-l-methyl-l / / -indazol-3-yl)- piperidine-2, 6-dione B507;3-(6-(4-(2-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- < / ]pyrimidin-2-yl)aniino)pyridin-3-yl)piperidin-4-yl)ethyl)piperazin-l-yl)-l -methyl- IH-indazol- 3 -yl)piperidine-2, 6-dione B508;(S)-3-(6-(4-(2-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2, 3 -< / ]pyrimidin-2-yl)amino)pyri din-3 -yl)piperidin-4-yl)ethyl)piperazin-l-yl)-l -methyl- 1 / / - indazol-3-yl)-3-methylpiperidine-2, 6-dione B509;( / ?)-3-(6-(4-(2-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-c / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)ethyl)piperazin-l-yl)-l-methyl-lH- indazol-3-yl)-3 -methylpiperidine-2, 6-dione B510; or3-(6-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-...

Claims

What is claimed is:

1. A compound of Formula (I):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein:A is a bond, heterocyclylene, or -S(Ch)-;E is heteroarylene, CG-M arylene, or heterocyclylene;L is a linker;X is -C(O)“ or a bond;R1is (i) hydrogen; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) -C(O)Rla, -C(O)ORla, -C(O)NRlbRl c, -C(O)SRla, ~C(NRla)NRlbRlc, -C(S)Rla, -C(S)ORla, ~C(S)NRlbRlc, -S(O)Rla, -S(O)2Rla, -S(O)NRlbRlc, or -S(O)2NRlbRlc;R2, R3, and R4are each independently (i) hydrogen, deuterium, cyano, halo, or nitro; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7.15 aralkyl, heteroaryl, or heterocyclyl; or (iii) C(O)Rla, C(O)ORla, C(O)NRlbRlc, - C(O)SRla, -C(NRia)NRlbRlc, -C(S)Rla, -C(S)ORla, -C(S)NRlbRlc, -ORla, -OC(O)Rla, -OC(O)ORla, -OC(O)NRlbRlc, -OC(O)SRla, -OC(NRla)NRlbRlc, -OC(S)Rla, -OC(S)ORla, -OC(S)NRlbRlc, -OS(O)Rla, -OS(O)2R!a, -OS(O)NRlbRlc, ~OS(O)2NRlbRlc, -NRlbRlc, -NRlaC(O)Rld, -NRlaC(O)ORld, -NRlaC(O)NRlbRlc, -NRlaC(O)SRld, ~NRlaC(NRld)NRlbRlc, ~NRlaC(S)Rld, -NRlaC(S)ORld, -NRlaC(S)NRlbRlc, -NRlaS(O)Rld, -NRlaS(O)2Rld, -NRlaS(O)NRlbRlc, -NRlaS(O)2NRlbRlc, -SRla, -S(O)Rla, -S(O)2Rla, -S(O)NRlbRlc, or -S(O)2NRlbRlc;wherein: each AEis independently a bond, -0- -N(Rlb)-, -S-, C1-6 alkylene, Ci-6 heteroalkylene, C2-6 alkenylene, C2-6 heteroalkenylene, C2-6 alkynylene, C2-6 heteroalkynylene, C3-10 cycloalkylene, C6-14 arylene, C7-15 aralkylene, heteroarylene, heterocyclylene, C1-6 heteroalkylene-Ce-ii arylene, C1-6 heteroalkylene-heterocyclylene, or C2-6 alkynylene-heterocyclylene; each XEis independently C(RE1) or N;YEis a bond, C1-6 alkylene, -0-, -S-, -S(0)-, -S(02>-, or --N(RE3)-;Z is -CH2- or -C(0)-; one of Z1, Z2, Z3, and Z4is C= and the remaining three of Z1, Z2, Z3, and Z4are each independently -C(RE4a)=; or Z1is a bond; one of Z2, Z3, and Z4is ~C=, and the remaining two of Z2, Z3, and Z4are each independently -C(RE4a):=:or -S-; each RE1is independently hydrogen, deuterium, halo, or C1-6 alkyl; each RE2, RE3, and RE5is independently hydrogen or C1-6 alkyl; each RE4is independently (i) deuterium, cyano, halo, or nitro; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) -C(0)Rla, -C(0)0Rla, -C(0)NRlbRlc, -C(O)SRla, -C(NRla)NRlbRlc, -C(S)Rla, -C(S)ORla, -C(S)NRlbRlc, -0Rla, -0C(0)Rla, -0C(0)0Rla, -0C(0)NRlbRlc, -OC(O)SRla, -0C(NRla)NRlbRlc, -OC(S)Rla, -OC(S)ORla, -0C(S)NRlbRlc, -OS(O)Rla, -OS(O)2Rla, -0S(0)NRlbRlc, -0S(0)2NRlbRlc, -NRlbRlc, -NRlaC(0)Rld, ~NRlaC(0)0Rld, -NRlaC(0)NRlbRlc, -NRlaC(0)SRld, ~NRlaC(NRld)NRlbRlc, ~NRlaC(S)Rld, ~NRlaC(S)0Rld, ~NRlaC(S)NRlbRlc, -NRlaS(0)Rld, ~NRlaS(0)2Rld, -NRlaS(0)NRlbRlc, -NRlaS(0)2NRlbRlc, -SRla, -S(O)Rla, -S(O)2Rla, -S(0)NRlbRlc, or -S(0)2NRlbRlc; each RE4ais independently hydrogen or RE4; each m is independently an integer of 0, 1, or 2; and each n is independently an integer of 0, 1, 2, or 3; andeach Rla, Rlb, Rlc, and Rldis independently hydrogen, deuterium, C1-6 alkyl, Ci-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-14 aryl, C--15 aralkyl, heteroaryl, or heterocyclyl; wherein each alkyl, alkylene, heteroalkyl, heteroalkylene, alkenyl, alkenylene, heteroalkenylene, alkynyl, alkynylene, heteroalkynylene, cycloalkyl, cycloalkylene, aryl, arylene, aralkyl, aralkylene, heteroaryl, heteroarylene, heterocyclyl, and heterocyclylene is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, wherein each Q is independently selected from: (a) deuterium, cyano, halo, imino, nitro, and oxo; (b) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-14 and, C7-15 aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; and (c) -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -C(O)SRa, ~C(NRa)NRbRc, -C(S)Ra, -C(S)ORa, -C(S)NRbRc, -ORa, -OC(O)Ra, -OC(O)ORa, -OC(O)NRbRc, -OC(O)SRa, -OC(NRa)NRbRc, -OC(S)Ra, -OC(S)ORa, -OC(S)NRbRc, -OP(O)(ORb)ORc, -OS(O)Ra, ~OS(O)2Ra, -OS(O)NRbRc, -OS(O)2NRbRc, -NRbRc, -NRaC(O)Rd, ~NRaC(O)ORd, -NRaC(O)NRbRc, -NRaC(O)SRd, -NRaC(NRd)NRbRc, -NRaC(S)Rd, -NRaC(S)ORd, -NRaC(S)NRbRc, -NRaS(O)Rd, -NRaS(O)2Rd, -NRaS(O)NRbRc, -NRaS(O)2NRbRc, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRbRc, and - S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rdis independently (i) hydrogen or deuterium; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; or (iii) Rband Rctogether with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa; wherein each Qais independently selected from: (a) deuterium, cyano, halo, nitro, imino, and oxo; (b) C1-6 alkyl, C 1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl; and (c) -C(O)Re, -C(O)ORe, C(O)NRfRs, -C(O)SRe, -C(NRe)NRfRg, -C(S)Re, -C(S)ORe, -C(S)NRfRg, -ORe, -OC(O)Re, -OC(O)ORe, -OC(O)NRfRg, OC(O)SRe, -OC(NRe)NRfR8, -OC(S)Re, -OC(S)ORe, -OC(S)NRfRg, -OP(O)(ORf)ORg, -OS(O)Re, -OS(O)2Re, -OS(O)NRfRg, -OS(O)2NRfRg, -NRfRg, -NReC(O)Rh, -NReC(O)ORf, -NReC(O)NRfRg, -NReC(O)SRf, -NReC(NRh)NRfRg, -NReC(S)Rh, -NReC(S)ORf, -NReC(S)NRfRg, -NReS(O)Rh, -NReS(O)2Rb, -NReS(O)NRfRs,-NReS(O)2NRfRs, -SRe, -S(O)Re, -S(O)2Re, -S(O)NRfRg, and -S(O)2NRfRg; wherein each Re, R\ Rg, and Rhis independently (i) hydrogen or deuterium, (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl; or (iii) Rfand R8together with the N atom to which they are attached form heterocyclyl.

2. The compound of claim 1, wherein E is Ce-14 arylene or heteroarylene, each optionally substituted with one or more substituents Q.

3. The compound of claim 1 or 2, wherein E is phenyl or monocyclic heteroarylene, each optionally substituted with one or more substituents Q.

4. The compound of any one of claims 1 to 3, having the structure of Formula (II):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein:Y is -C(R> or -N=;R5is hydrogen or R5a; each R5ais independently (i) deuterium, cyano, halo, or nitro; (ii) C1-6 alkyl, C1-6 heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or (iii) -C(O)Rla, -C(O)ORla, -C(O)NRlbRlc, -C(O)SRla, -C(NRla)NRlbRlc, -C(S)Rla, -C(S)ORla, -C(S)NRlbRk, -ORla, -OC(O)Rla, -OC(O)ORla, -OC(O)NRibRk, -OC(O)SRla, “0C(NRla)NRlbRlc, -OC(S)Rla, -OC(S)ORla, -OC(S)NRlbRk, -OS(O)Rla, -OS(O)2Rla, -OS(O)NRlbRlc, -OS(O)2NRlbRlc, -NRlbRlc, -NRlaC(O)Rld, -NRlaC(O)ORld, -NRlaC(O)NRlbRlc, -NRlaC(O)SRld, -NRlaC(NRld)NRlbRlc, -NRlaC(S)Rld, -NRlaC(S)ORld, -NRlaC(S)NRlbRlc, -NRlaS(O)Rld, -NR!aS(O)2Rld, -NRlaS(O)NRlbRlc, -NRlaS(O)2NRlbRlc, -SRla, -S(O)Rla, -S(O)2Rla, -S(O)NRlbRk, or -S(O)2NRlbRlc; and a is an integer of 0, 1, 2, or 3.

5. The compound of claim 1, wherein E is heterocyclylene, optionally substituted with one or more substituents Q.

6. The compound of claim 1 or 5, wherein E is monocyclic heterocyclylene, each optionally substituted with one or more substituents Q.

7. The compound of claim 1, 5, or 6, wherein E is 6-membered heterocyclylene, optionally substituted with one or more substituents Q.

8. The compound of any one of claims 1 and 5 to 7, wherein E is piperidindiyl, optionally substituted with one or more substituents Q.

9. The compound of any one of claims 1 and 5 to 8, having the structure of Formula(IIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein: each R6is independently (i) deuterium, cyano, halo, or nitro; (ii) C1-6 alkyl, Ci-e heteroalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one or more substituents Q; or (iii) -C(O)Rla, -C(O)ORla, -C(O)NRlbRlc, -C(O)SRla, -C(NRla)NRlbRlc, -C(S)Rla, -C(S)ORla, -C(S)NRlbRlc, -ORla, -OC(O)Ria, -OC(O)ORla, -OC(O)NRlbRlc, ~OC(O)SRla, OC(NRla)NRlbRlc, -OC(S)Ria, -OC(S)ORla, -OC(S)NRlbRlc, -OS(O)Rla, ~OS(O)2Rla, -OS(O)NRlbRlc, -OS(O)2NRlbRlc, -NRlbRl c, -NRlaC(O)Rld, -NRlaC(O)ORld, -NRlaC(O)NRlbRlc, -NRlaC(O)SRld, -NRlaC(NRld)NRlbRlc, -NRlaC(S)Rld, -NRlaC(S)ORld, -NRlaC(S)NRlbRlc, -NRlaS(O)Rld, -NRlaS(O)2Rld, -NRlaS(O)NRlbRle, -NRlaS(O)2NRlbRlc, -SRla, -S(O)Rla, -S(O)2Rla, -S(O)NRlbRlc, or -S(O)2NRlbRlc, and b is an integer of 0, 1 , 2, 3, or 4.

10. The compound of any one of claims 1 to 9, X is a bond.

11. The compound of any one of claims 1 to 9, X is --C(O)-12. The compound of any one of claims 1 to 11, wherein A is a bond or heterocyclylene, optionally substituted with one or more substituents Q.

13. The compound of any one of claims 1 to 12, wherein A is monocyclic heterocyclylene, optionally substituted with one or more substituents Q.

14. The compound of any one of claims 1 to 13, wherein A is 6-membered heterocyclylene, optionally substituted with one, two, or three substituents Q.

15. The compound of any one of claims 1 to 14, wherein A is piperidin-1 ,4-diyl or piperazin- 1,4-diyl, each optionally substituted with one, two, or three substituents Q.

16. The compound of any one of claims 4, 10, and 12, having the structure of Formula (II A):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

17. The compound of any one of claims 4, 11, and 12, having the structure of Formula (IIB):or an enantiomer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; ora pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

18. The compound of any one of claims 4, 10, and 12 to 15, having the structure of Formula (IIIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

19. The compound of any one of claims 4 and 11 to 15, having the structure of Formula (IIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

20. The compound of any one of claims 1 to 11, wherein A is -S(O2)-.

21. The compound of any one of claims 9, 11, and 20, having the structure of Formula (IIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or morediastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

22. The compound of any one of claims 1 to 21, wherein REis a moiety having the structure of Formula (EC-I):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

23. The compound of any one of claims 1 to 22, wherein REis a moiety’ having the structure of Formula (EC-I-a):(EC-I-a)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

24. The compound of any one of claims 1 to 23, wherein REis a moiety having the structure of Formula (EC-I-c):(EC-I-c)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mi xture of two or more tautomers, or an i sotopic variant thereof.

25. The compound of any one of claims 1 to 23, wherein REis a moiety having the structure of Formula (EC-I-d):(EC-T-d)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

26. The compound of any one of claims 1 to 23, wherein REis a moiety having the structure of Formula (EC-I-f):(EC-I-f)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

27. The compound of any one of claims 1 to 23, wherein REis a moiety having the structure of Formula (EC-I-g):(EC-I-g)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

28. The compound of any one of claims 1 to 22, wherein REis a moiety having the structure of Formula (EC-I-h):(EC-I-h)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

29. The compound of claim 27, wherein RE3is hydrogen.

30. The compound of any one of claims 1 to 23, wherein REis a moiety having the structure of:or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mi xture of two or more tautomers, or an i sotopic variant thereof.

31. The compound of any one of claims 1 to 23 and 30, wherein REis a moiety having the structure of:0 „r1 EC-A16 , or an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

32. The compound of any one of claims 1 to 21, wherein REis a moiety’ having the structure of Formula (EC -II):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

33. The compound of any one of claims 1 to 21 and 32, wherein REis a moiety having the structure of Formula (EC-II-b):(EC-II-b)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mi xture of two or more tautomers, or an i sotopic variant thereof.

34. The compound of any one of claims 1 to 21 and 32, wherein REis a moiety having the structure of Formula (EC-II-c):(EC-II-c)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

35. The compound of any one of claims 1 to 21 and 32, wherein REis a moiety having the structure of Formula (EC-II-e):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

36. The compound of any one of claims 1 to 21 and 32, wherein REis a moiety having the structure of Formula (EC-II-f):(EC-II-f)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

37. The compound of any one of claims 1 to 21 and 32, wherein REis a moiety having the structure of:or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or morediastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

38. The compound of any one of claims 1 to 21 , 32, and 37, wherein REis a moiety having the structure of:or an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

39. The compound of any one of claims 1 to 21 , wherein REis a moiety having the structure of Formula (EC -III):or an enantiomer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

40. The compound of any one of claims 1 to 21 and 39, wherein REis a moiety having the structure of Formula (EC-III-c):or an enanti omer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

41. The compound of any one of claims 1 to 21 and 39, wherein REis a moiety having the structure of Formula (EC-III-d):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

42. The compound of any one of claims 1 to 21 and 39, wherein REis a moiety having the structure of Formula (EC-III-e):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

43. The compound of any one of claims 1 to 21 and 39, wherein REis a moiety having the structure of Formula (EC-III-h):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

44. The compound of any one of claims 1 to 21, 39, and 43, wherein REis a moiety having the structure of Formula (EC-III-i):(EC-III-i)or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

45. The compound of any one of claims 1 to 21 and 39, wherein REis a moiety having the structure of Formula (EC-III-k):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

46. The compound of any one of claims 1 to 21 and 39, wherein REis a moiety having the structure ofor an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

47. The compound of any one of claims 1 to 21, 39, and 46, wherein REis a moiety having the structure of:EC-C13 or an enantiomer, a mixture of enantiomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof.

48. The compound of claim 4 or 10, having the structure of Formula (IVA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

49. The compound of any one of claims 4, 10, and 48, having the structure of Formula (VA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

50. The compound of any one of claims 4, 10, and 48, having the structure of Formula (VIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

51. The compound of any one of claims 4, 10, and 48, having the structure ofor an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

52. The compound of any one of claims 4, 10, and 48, having the structure of Formula (VIII A):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

53. The compound of claim 4 or 10, having the structure of Formula (IXA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

54. The compound of any one of claims 4, 10, and 53, having the structure of Formula (XA):or an enanti omer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; ora pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

55. The compound of any one of claims 4, 10, and 53, having the structure of Formula (XIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

56. The compound of any one of claims 4, 10, and 53, having the structure of Formula (XII A):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

57. The compound of any one of claims 4, 10, and 53, having the structure of Formula (XIIIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

58. The compound of claim 4 or 10, having the structure of Formula (XIVA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

59. The compound of any one of claim s 4, 10, and 58, having the structure of Formula (XV A):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

60. The compound of any one of claims 4, 10, and 58, having the structure of Formula (XVIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

61. The compound of any one of claims 4, 10, and 58, having the structure of Formula (XVIIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

62. The compound of any one of claims 4, 10, and 58, having the structure ofFormula (XVIII A):or an enantiomer, a mixture of enanti omers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

63. The compound of claim 4 or 10, having the structure of Formula (XIXA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

64. The compound of any one of claims 4, 10, and 63, having the structure of Formula (XX A):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

65. The compound of any one of claims 4, 10, and 63, having the structure ofFormula (XXI A):or an enantiomer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

66. The compound of any one of claims 4, 10, and 63, having the structure ofFormula (XXII A):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

67. The compound of any one of claims 4, 10, and 63, having the structure ofFormula (XXIII A):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

68. The compound of claim 4 or 10, having the structure of Formula (XXV A):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

69. The compound of claim 4 or 10, having the structure of Formula (XXVIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mi xture of two or more tautomers, or an i sotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

70. The compound of claim 4 or 10, having the structure of Formula (XXVIIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mi xture of two or more tautomers, or an i sotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

71. The compound of claim 4 or 10, having the structure of Formula (XXIXA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

72. The compound of claim 4 or 10, having the structure of Formula (XXXA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

73. The compound of claim 4 or 10, having the structure of Formula (XXXIA):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

74. The compound of claim 9 or 11, having the structure of Formula (IVB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

75. The compound of any one of claims 9, 11, and 74, having the structure ofFormula (VB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

76. The compound of any one of claims 9, 11, and 74, having the structure of Formula (VIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

77. The compound of any one of claims 9, 11, and 74, having the structure of Formula (VIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mi xture of two or more tautomers, or an i sotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

78. The compound of any one of claims 9, 11 , and 74, having the structure of Formula (VIIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

79. The compound of claim 9 or 11, having the structure of Formula (IXB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

80. The compound of any one of claims 9, 11, and 79, having the structure of Formula (XB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

81. The compound of any one of claims 9, 11 , and 79, having the structure ofFormula (XIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

82. The compound of any one of claims 9, 11 , and 79, having the structure of Formula (XIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

83. The compound of any one of claim s 9, 11, and 79, having the structure of Formula (XB1B):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

84. The compound of claim 9 or 11, having the structure of Formula (XIVB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

85. The compound of any one of claim s 9, 11, and 84, having the structure of Formula (XVB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

86. The compound of any one of claims 9, 11, and 84, having the structure of Formula (XVIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; ora pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

87. The compound of any one of claims 9, 11 , and 84, having the structure of Formula (XVIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

88. The compound of any one of claims 9, 11, and 84, having the structure ofFormula (XVIIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

89. The compound of claim 9 or 11 , having the structure of Formula (XIXB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

90. The compound of any one of claims 9, 11 , and 89, having the structure ofFormula (XXB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

91. The compound of any one of claims 9, 11, and 89, having the structure of Formula (XXIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

92. The compound of any one of claims 9, 11, and 89, having the structure of Formula (XXIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

93. The compound of any one of claims 9, 11 , and 89, having the structure of Formula (XXIIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

94. The compound of claim 9 or 11, having the structure of Formula (XXVB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

95. The compound of claim 9 or 11, having the structure of Formula (XXVIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

96. The compound of claim 9 or 11, having the structure of Formula (XXVIIB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

97. The compound of claim 9 or 11, having the structure of Formula (XXIXB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mi xture of two or more tautomers, or an i sotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

98. The compound of claim 9 or 11, having the structure of Formula (XXXB):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

99. The compound of claim 9 or 11, having the structure of Formula (XXXIB):or an enantiomer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

100. The compound of any one of claims 21, having the structure of Formula (IIIC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

101. The compound of any one of claims 21 or 100, having the structure of Formulaor an enanti omer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

102. The compound of any one of claims 21 or 100, having the structure of Formula(VC):or an enantiomer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

103. The compound of any one of claims 21 or 100, having the structure of Formula(VIC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mi xture of two or more tautomers, or an i sotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

104. The compound of any one of claims 21 or 100, having the structure of Formula(VIIC):or an enantiomer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; ora pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

105. The compound of any one of claims 21, having the structure of Formula (VIIIC):or an enanti omer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

106. The compound of any one of claims 21 or 105, having the structure of Formula(IXC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.107, The compound of any one of claims 21 or 105, having the structure of Formula(XC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mi xture of two or more tautomers, or an i sotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

108. The compound of any one of claims 21 or 105, having the structure of Formula(XIC):or an enantiomer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

109. The compound of any one of claims 21 or 105, having the structure of Formula(XIIC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

110. The compound of any one of claims 21, having the structure of Formula (XIVC):or an enanti omer, a mixture of enantiomers, a di astereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

111. The compound of any one of claim s 21 , having the structure of F ormula (XV C) :or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

112. The compound of any one of claims 21, having the structure of Formula (XIVC):or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereom ers, a tautomer, a mi xture of two or more tautomers, or an i sotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

113. The compound of any one of claims 1 to 112, wherein R1is C1-6 alkyl or C3-10 cycloalkyl, each optionally substituted with one or more substituents Q.

114. The compound of any one of claims 1 to 113, wherein R1is C3-10 cycloalkyl, optionally substituted with one or more substituents Q.

115. The compound of any one of claims 1 to 114, wherein R1is monocyclic C3-10 cycloalkyl, optionally substituted with one or more substituents Q.

116. The compound of any one of claims 1 to 115, wherein R1is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, each optionally substituted with one, two, or three substituents Q.

117. The compound of any one of claims 1 to 113, wherein R1is cyclopentyl, 2- hydroxy -2-methylcyclopentyl, or118. The compound of any one of claims 1 to 117, wherein R2is (i) cyano or halo; (ii) C1-6 alkyl, C7-15 aralkyl, or heteroaryl, each optionally substituted with one or more substituents Q; or (iii) -C(O)Rla, -C(O)ORla, -C(O)NRlbRlc, -ORla, or -NRlbRlc.

119. The compound of any one of claims 1 to 118, wherein R2is -C(O)Rla120. The compound of any one of claims 1 to 118, wherein R2is -C(O)NRlbRlc.121 . The compound of any one of claims 1 to 118, wherein R2is cyano, fluoro, chloro, bromo, iodo, methyl, ethyl, isopropyl, hydroxymethyl, ethoxymethyl, benzyl, oxazol-5-yl, acetyl, hydroxy carbonyl, ethoxycarbonyl, methyl aminocarbonyl, dimethylaminocarbonyl, 2-ethoxy- ethoxy, or amino.

122. The compound of any one of claims 1 to 118, wherein R2is difluoromethyl, acetyl, or dimethylaminocarbonyl.

123. The compound of any one of claims 1 to 122, wherein R3is hydrogen, deuterium, or C1-6 alkyl, optionally substituted with one or more substituents Q.

124. The compound of any one of claims 1 to 123, wherein R3is hydrogen, deuterium, or methyl.

125. The compound of any one of claims 1 to 124, wherein R3is hydrogen.

126. The compound of any one of claims 1 to 124, wherein R3is methyl.

127. The compound of any one of claims 1 to 126, wherein R4is hydrogen.

128. The compound of any one of the preceding claims, wherein Y is ~C(R5)=.

129. The compound of any one of the preceding claims, wherein R3is hydrogen, deuterium, halo, or C1-6 alkyl, optionally substituted with one or more substituents Q.

130. The compound of any one of the preceding claims, wherein R5is hydrogen, fluoro, chloro, methyl, or ethyl.

131. The compound of any one of the preceding claims, wherein R5is hydrogen.

132. The compound of any one of the preceding claims, wherein Y is -N=.

133. The compound of any one of the preceding claims, wherein a is an integer of 1.

134. The compound of any one of the preceding claims, wherein R5ais deuterium, halo, or C1-6 alkyl, optionally substituted with one or more substituents Q.

135. The compound of any one of the preceding claims, wherein R3ais hydrogen, fluoro, chloro, methyl, or ethyl.

136. The compound of any one of the preceding claims, wherein a is an integer of 0.

137. The compound of any one of the preceding claims, wherein RE1is hydrogen.

138. The compound of any one of claims 1 to 137, wherein RE2is hydrogen.

139. The compound of any one of the preceding claims, wherein n is an integer of 1 or 2.

140. The compound of any one of the preceding claims, wherein each RE4is independently deuterium, halo, or C1-6 alkyl, optionally substituted with one or more substituents Q141. The compound of any one of the preceding claims, wherein each RE4is independently fluoro, chloro, methyl, isopropyl, or trifluoromethyl.

142. The compound of any one of the preceding claims, wherein RE4is methyl or trifluoromethyl.

143. The compound of any one of the preceding claims, wherein n is an integer of 0.

144. The compound of any one of the preceding claims, wherein RE4ais hydrogen,deuterium, or halo.

145. The compound of any one of the preceding claims, wherein RE4ais hydrogen, deuterium, fluoro, or chloro.

146. The compound of any one of the preceding claims, wherein RE4ais fluoro.

147. The compound of any one of the preceding claims, wherein RE3is hydrogen or Ci- 6 alkyl, optionally substituted with one or more substituents Q.

148. The compound of any one of the preceding claims, wherein RE5is hydrogen or methyl.

149. The compound of any one of the preceding claims, wherein RE5is methyl.

150. The compound of any one of the preceding claims, wherein AEis (i) a bond; or (ii) C2-6 alkynylene, heterocyclylene, C1-6 heteroalkylene-Ce-u arylene, C1-6 alkylene- heterocyclylene, or C2-6 alkynylene-heterocyclylene, each of which is optionally substituted with one or more substituents Q.

151. The compound of any one of the preceding claims, wherein AEis (i) a bond; or (ii) heterocyclylene, C1-6 heteroalkylene-Ce-u arylene, or C1-6 alkylene-heterocyclylene, each of which is optionally substituted with one or more substituents Q.

152. The compound of any one of the preceding claims, wherein AEis (i) a bond; or (ii) heterocyclylene, C1-6 heteroalkylene-C6-i4 arylene, or C1-6 alkylene-monocyclic heterocyclylene, each of which is optionally substituted with one or more substituents Q.

153. The compound of any one of the preceding claims, wherein AEis (i) a bond; or (ii) heterocyclylene, C1-6 heteroalkylene-phendiyl, or C1-6 alkylene-(6-membered heterocyclylene), each of which is optionally substituted with one or more substituents Q.

154. The compound of any one of the preceding claims, wherein AEis a bond, piperidin-l,3-diyl, piperidin-l,4-diyl, piperaz-l,4-diyl, (phen-l,4-diyl)oxymethanediyl,(piperidin- 1 ,4-diyl )ethynediyl,155. The compound of any one of the preceding claims, wherein AEis a bond,156. The compound of any one of claims 1 to 155, wherein L has the structure of: -ZL-(RL-ZL)z- wh erein: each RLis independently C1-10 alkylene, C2-10 alkenylene, C2-10 alkynylene, C3-10 cycloalkylene, C6-14 arylene, heteroarylene, or heterocyclylene, each of which is optionally substituted with one or more substituents Q; each ZLis independently a bond, -C(O)-, -C(O)O- -C(O)NRlb-, -C(O)S- -C(NRla)NRlb- -C(S)-, -C(S)O-, -C(S)NRlb-, -0- -OC(O)O-, -OC(O)NRlb-, -OC(O)S- -OC(NRla)NRlb-, -OC(S)-, -OC(S)O-, -OC(S)NRlb- -OS(O)-, -OS(O)2-, -OS(O)NRlb- -OS(O)2NRlb-, -NRlb- -NRlaC(O)NRlb- -NRlaC(O)S- -NRlaC(NRld)NRlb- -NRlaC(S)NRlb- -NRlaS(O)NRlb~, -NRlaS(O)2NRlb- -S-, -S(O)-, -S(O)2-, -S(O)NRlb-, or -S(O)2NRlb- and z is an integer of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

157. The compound of claim 156, wherein each RLis independently Ci-io alkylene, C2- 10 alkynylene, C3-10 cycloalkylene, C6-14 arylene, heteroarylene, or heterocyclylene, each of which is optionally substituted with one or more substituents Q.

158. The compound of claim 156 or 157, wherein each RLis independently methanediyl, ethane- 1,2-diyl, propane- 1,3 -diyl, butane- 1,4-diyl, pentane-l,5-diyl, hexane-1,6- diyl, heptane-l,7-diyl, octane- 1,8 -diyl, nonane- 1,9-diyl, decane- 1, 10-diyl, undecane- 1 , 1 1 -diyl,dodecane-1,12-diyl, tridecane-1, 13-diyl, ethyne- 1,2-diyl, cyclobutane-1, 3-diyl, cyclopentane- 1, 3-diyl, cyclohexane-1, 3-diyl, cyclohexane-1, 4-diyl, cycloheptane- 1,3 -diyl, cycloheptane- 1,4- diyl, bicyclo[2.2.2]octane-l, 4-diyl, phen-1, 3-diyl, phen-1, 4-diyl, pyrazoi- 1,3 -diyl, pyrazol-1,4- diyl, imidazol-1, 4-diyl, 1, 2, 3-triazol-l, 4-diyl, pyrimidin-2, 4-diyl, pyrimidin-2, 5-diyl, 5, 6, 7, 8, 9, 10-hexahydrocycloocta[d]-pyridazin-l,7-diyl, pyrazoli din- 1,3 -diyl, pyrazolidin-1,4- diyl, l,3-dioxan-2, 5-diyl, piperazin-1, 4-diyl, piperidin-1, 3-diyl, piperidin-1, 4-diyl, or 3,9- diazaspiro[5.5]-undecane-3,9-diyl, each of which is optionally substituted with one or more substituents Q.

159. The compound of any one of claims 156 to 158, wherein each ZLis independently a bond, -C(O)-, -C(O)NRlb- -O-, -OC(O)NRlb-, -NRlb-, or -NRlaC(O)NRlb-.

160. The compound of any one of claims 156 to 159, wherein each ZLis independently a bond, -C(O)-, -C(O)O- -C(O)NH- -OC(O)NH-, -O-, XI I , -N(CH3)~, or -NHC(O)NH-.

161. The compound of any one of claims 156 to 160, wherein z is an integer of 1, 2, 3, or 4.

162. The compound of claim 156, wherein each RLis independently methanediyl, ethane- 1,2-diyl, propane-1, 3-diyl, cyclohex- 1,3 -diyl, cyclohex-1, 4-diyl, phen- 1,3 -diyl, phen-1, 4- diyl, azetidin-1, 3-diyl, piperazin- 1, 4-diyl, piperidin-1 , 3-diyl, piperidin-1, 4-diyl, morpholin-2,4- diyl, 4,7-diazaspiro[2.5]octan-4,7-diyl, 3-azabicyclo[3.2.1]octan-3,8-diyl, 8-azabicyclo[3.2.1]- octan-3,8-diyl, 3,8-diazabicyclo[3.2.1]octan-3,8-diyl, or 2,7-diazaspiro[3.5]nonan-2,7-diyl, each optionally substituted with one, two, or three substituents, each of which is independently fluoro or methyl; each ZLis independently a bond or -O-; and z is an integer of 2, 3, 4, or 5163. The compound of claim 156 or 162, wherein each RLis independently methanediyl, ethane- 1,2-diyl, 1,1 -difluoroethane- 1,2-diyl, propane-1, 3-diyl, cyclohex- 1,3 -diyl, cy cl ohex-1, 4-diyl, phen- 1,3 -diyl, phen-1, 4-diyl, azetidin-1, 3-diyl, 3-fluoroazetidin-l, 3-diyl, piperazin- 1, 4-diyl, 2-methylpiperazin-l, 4-diyl, piperidin-1, 3 -diyl, piperidin-1, 4-diyl, 4-fluoro- piperi din- 1, 4-diyl, morpholin-2, 4-diyl, 4,7-diazaspiro[2.5]octan-4,7-diyl, 3-azabicyclo[3.2.1]- octan-3,8-diyl, 8-azabi cyclop.

2. l]octan-3,8-diyl, 3,8-diazabicyclo[3.

2. l]octan-3,8-diyl, or 2,7- diazaspiro[3.5]nonan-2,7-diyl; each ZLis independently a bond or -O-; and z is an integer of 2,3, 4, or 5.

164. The compound of any one of claims 1 to 156, wherein L is:

165. The compound of any one of claims 1 to 156, wherein L is:

166. The compound of any one of claims 1 to 156, wherein L is:

167. The compound of any one of the preceding claims, wherein Z is -CH2-.

168. The compound of any one of the preceding claims, wherein m is an integer of 1.

169. A compound of:7-cyclopentyl-2-((4-((2-(4-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperazin-l-yl)ethyl)carbamoyl)phenyl)amino)-AyV-dimethyl-7H-pyrrolo[2,3-(7]pyrimidine-6- carboxamide A101;7-cyclopentyl-2-((4-((4-(4-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperazin-l-yl)butyl)carbamoyl)phenyl)amino)-7V,Az-dimethyl-7 / 7-pyrrolo[2,3-<7]pyrimidine-6- carboxamide Al 02;7-cyclopentyl-2-((4-((6-(4-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperazin-l-yl)hexyl)carbamoyl)phenyl)amino)-A7,A''-dimethyl-7 / / -pyrrolo[2,3-t(jpyrimidine-6- carboxamide A103;7-cyclopentyl-2-((4-(4-(2-(4-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperazin-l-yl)ethyl)piperazin-l-yl)phenyl)amino)-7V,A / r-dimethyl-7H-pyrrolo[2,3-t / ]pyrimidine- 6-carboxamide A104,7-cyclopentyl-2-((4-(4-(4-(4-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperazin-l-yi)butyl)piperazin-l-yi)phenyi)amino)-Ar,A7-dimethyl-77f-pyrrolo[2,3-J|pyrimidine- 6-carboxamide A105;7-cyclopentyl-2-((4-(4-(2-(l-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperidin-4-yl)ethyl)piperazin-l-yl)phenyl)amino)-Ar,A'T-dimethyl-7 / f-pyrrolo[2,3-^pyrimidine- 6-carboxamide A106, 7-cyclopentyl-2-((4-(4-(4-(l-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperidin-4-yl)butyl)piperazin-l-yl)phenyl)amino)-Ar,Ar-dimethyl-7 / / -pyrrolo[2,3-^pyrimidine- 6-carboxamide A107;7-cyclopentyl-2-((4-(4-(2-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetamido)- ethyl)piperazin-l-yl)phenyl)amino)-Ar,Ar-dimethyl-7Z / -pyrrolo[2,3-i7]pyrimidine-6-carboxamide A108;7-cyclopentyl-2-((4-(4-(2-(2-(3-(2,6-dioxopiperidin-3-yl)-4-methylphenoxy)- acetamido)ethyl)piperazin-l-yl)phenyl)amino)-Ar,AMimethyl-7Z / -pyrrolo[2,3-<7]pyrimidine-6- carboxamide A109;7-cyclopentyl-2-((4-(4-(2-(2-(3-(2,6-dioxopiperidin-3-yl)-4-(trifluoromethyl)- phenoxy)acetamido)ethyl)piperazin-l-yl)phenyl)amino)-A’,A'r-dimethyl-7H-pyrrolo[2,3-tf|- pyrimidine-6-carboxamide A110;7-cyclopentyl-2-((4-(4-(3-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)acetamido)- propyl)piperazin-l-yl)phenyl)amino)-A7,A / -dimethyl-7H-pyrrolo[2,3-t(|pyrimidine-6-carboxamide Alli;7-cy cl opentyl-2-(( 4-(4-(3 -(2-(3 -(2, 6-dioxopiperidin-3 -yl)-4-methyl phenoxy)- acetamido)propyl)piperaziii-l-yl)phenyl)amino)-Af,7V-dimethyl-7 / / -pyrrolo[2,3-J]pyrimidine-6- carboxamide Al 12;7-cyclopentyl-2-((4-(4-(3-(2-(3-(2,6-dioxopiperidin-3-yl)-4-(trifluoromethyl)- phenoxy)acetamido)propyl)piperazin-l-yl)phenyl)amino)-A',Ar-dimethyl-7 / / -pyrrolo[2,3-J|- pyrimidine-6-carboxamide Al 13;7-cyclopentyl-2-((4-((2-(4-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperazin-l-yl)ethyl)carbamoyl)phenyl)amino)-A,A’-dimethyl-7 / / -pyrrolo[2,3-^]pyrimidine-6- carboxamide Al 14;7-cyclopentyl-2-((4-((4-(4-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)- piperazin-l-yl)butyl)carbamoyl)phenyl)amino)-A',ALdimethyl-7JH-pyrrolo[2,3-J]pyrimidine-6- carboxamide Al 15;7-cyclopentyl-2-((4-((6-(4-(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)acetyl)-piperazin-l-yl)hexyl)carbamoyl)phenyl)amino)-A’,Ar-dimethyl-7 / 7-pyrrolo[2,3-<7]pyriniidine-6- carboxamide Al 16;7-cyclopentyl-2-((4-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- phenyl)amino)-A",A-dimethyl-7 / / -pyrroio[2,3-t7]pyrimidine-6-carboxamide A117;7-cyclopentyl-2-((4-(4-(4-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yl)- plienyl)amino)-7V,A-dimethyl-7 / 7-pyrrolo[2,3-^pyrimidine-6-carboxamide A118;7-cyclopentyl-2-((4-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l-yl)- phenyl)aniino)-A7Ar-dimethyl-7Z7-pyrrolo[2,3-J]pyrimidine-6-carboxamide A119;7-cyclopentyl-2-((4-(4-(3-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l-yl)- phenyl)amino)-?' / ,A'-dimethyl-7 / 7-pyrrolo[2,3-<7]pyrimidine-6-carboxamide Al 20;7-cyclopentyi-2-((4-(4-(2-(3-(2,6-dioxopiperidin-3-yl)phenoxy)ethyl)piperazin-l- yl)phenyl)amino)-Ar,Ar-dimethyl-7Z / -pyrrolo[2,3-t(]pyrimidine-6-carboxamide A121;7-cyclopentyl-2-((4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethyl)phenyl)aniino)-A7,A7-dimethyl-7 / 7-pyiTolo[2,3-J]pyrimidine-6-carboxamide A122;7-cyclopentyl-2-((4-(2-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazm-l-yl)- ethyl)phenyl)amiiio)-AT,Ar-dimethyl-727-pyrrolo[2,3-i7]pyrimidine-6-carboxaniide A123;7-cyclopentyl-2-((4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethoxy)phenyl)amino)-AT,A-dimethyl-72 / -pyrrolo[2,3-J]pyrimidine-6-carboxaniide A124;7-cyclopentyl-2-((4-(2-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethoxy)phenyl)amino)-A7A-dimethyl-7 / / -pyrrolo[2,3-tZ]pyrimidiiie-6-carboxamide A125;7-cyclopentyl-2-((4-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)phenyl)amino)-A,Ar-dimetliyl-7JH-pyrrolo[2,3-< / ]pyrimidine-6-carboxamide A126;7-cyclopentyl-2-((4-(4-(l-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)phenyl)amino)-AAV-dimethyl-7J7-pyrrolo[2,3-t7]pyrimidine-6-carboxamide A127;7-cyclopentyi-2-((4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yl)- ethyl)phenyl)amino)-A'r,A’-dimethyl-7 / Z-pyrrolo[2,3-^]pyrimidine-6-carboxamide A128;7-cyclopentyl-2-((4-(2-(4-(3-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yl)- ethyl)phenyl)amino)-A7,A7-dimethyl-7H-pyrrolo[2,3-t7]pyrimidine-6-carboxamide A129;7-cyclopentyl-2-((4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yl)- ethoxy)phenyl)amino)-A,A-dimethyl-7 / / -pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A130;7-cyclopentyl-2-((4-(2-(4-(3-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yl)-ethoxy)phenyl)amino)-A'r,A-dimethyl-7 / 7-pyrrolo[2,3-<7]pyrimidine-6-carboxamide A131;7-cyclopentyl-2-((4-((4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)methyl)phenyl)amino)-A?,Ar-dimethyl-7 / 7-pyrroIo[2,3-J|pyrimidine-6- carboxamide A132;7-cyclopentyl-2-((4-(2-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)ethoxy)phenyl)amino)-Arr / V-dimethyl-7J7-pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A133;7-cyclopentyl-2-((4-(2-(4-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l -yl)- piperidin-l-yl)ethoxy)phenyl)amino)-A,Az-dimethyl-7 / / -pyrrolo[2,3-o0pyrimidine-6-carboxamide A134;7-cyclopentyl-2-((4-(2-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4- yl)piperazin-l-yl)ethyl)phenyl)amino)-A'',7V-dimethyl-7flr-pyrrolo[2,3-J]pyrimidine-6- carboxamide A135;7-cyclopentyl-2-((4-(2-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)ethyl)phenyl)amino)-JV,A7-dimethyl-7 / f-pyrrolo[2,3-< / |pyrimidine-6-carboxamide A136;7-cyclopentyl-2-((4-(2-(4-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l -yl)- piperidin-l-yl)ethyl)phenyl)amino)-A',jV-dimethyl-777-pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A137;7-cyclopentyi-2-((4-(4-(l-(4-(2,6-dioxopiperidin-3-yl)benzyl)piperidin-4- yl)piperazin-l-yl)phenyl)amino)-Az,A’-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide A138;7-cyclopentyl-2-((4-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperidin-4-yl)- piperazin- 1 -yl)phenyl)amino)-A^V-dimethyl-7 / f-pyrrolo[2,3 -tZ]pyrimidine-6-carboxamide A139;7-cyclopentyi-2-((4-(4-(l-(3-(2,6-dioxopiperidin-3-yl)phenethyl)piperidin-4-yl)- piperazin-l-yi)phenyl)amino)-A,A / -dimethyl-7 / Z-pyrrolo[2,3-^pyrimidine-6-carboxamide A140;7-cyclopentyl-2-((4-(4-((l-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- methyl)piperazin-l-yl)phenyl)amino)-Ar,7V-dimethyl-7 / / -pyrrolo[2,3-<T]pyrimidine-6- carboxamide A141;7-cyclopentyl-2-((4-(4-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- methyi)piperazin-l-yl)phenyl)amino)-A7,Air-dimethyl-7ZZ-pyrrolo[2,3-c(|pyrimidine-6-carb oxami de Al 42;7-cyclopentyl-2-((4-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- ethyl)piperazin-l-yl)phenyl)amino)-Ar,Ar-dimethyl-77f-pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A143;7-cyclopentyl-2-((4-(4-(2-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- ethyl)piperazin-l-yl)phenyl)amino)-Ar,A7-dimethyl-7 / 7-pyrrolo[2,3-<7]pyrimidine-6-carboxamide A144;7-cyclopentyl-2-((5-(4-(3-(4-(4-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yl)- phenyl)piperazin-l-yi)pyridin-2-yl)amino)-Ar,A’-dimethyl-7 / / -pyrrolo[2,3-dr]pyrimidine-6- carboxamide Al 45;7-cyclopentyl-2-((5-(4-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l- yl)phenyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,Ar-dimethyl-7H-pyrrolo[2,3-<7]pyrimidine-6- carboxamide A146;7-cyclopentyl-2-((5-(4-(3-(4-(3-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l- yl)phenyl)piperazin-l-yl)pyridin-2-yl)amino)-A / 7-dimethyl-77f-pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A147;7-cyclopentyl-2-((5-(4-(4-(4-(4-(2,6-dioxopiperidm-3-yl)benzyl)piperazin-l-yl)- phenyl)piperazin-l-yl)pyridin-2-yl)amino)-AT,A’-dimethyl-7 / / -pyrrolo[2,3-< / |pyrimidine-6- carboxamide Al 48;7-cyclopentyl-2-((5-(4-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l- yl)phenyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,Az-dimethyl-77 / -pyrrolo[2,3-tZ]pyrimidine-6- carboxamide A149;7-cyclopentyl-2-((5-(4-(4-(4-(3-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l- yl)phenyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,Ar-diniethyl-77f-pyrrolo[2,3-c / ]pyrimidine-6- carboxamide A150;7-cyclopentyl-2-((5-(4-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- benzyl)piperazin-l-yl)pyridin-2-yl)amino)-A’,AT-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6- carb oxami de A 151 ;7-cyclopentyl-2-((5-(4-(4-((4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- methyl)phenyl)piperazin-l-yl)pyridin-2-yl)amino)-A’,A-dimethyl-7AF-pyiTolo[2,3-J]pyrimidine- 6-carboxamide A152;7-cy cl opentyl-2-((5 -(4-(4-(4-(3 -(2, 6-dioxopiperidin-3 -yl)pheny l)piperazin- 1 -y I )- benzyl)piperazin-l-yl)pyridin-2-yl)amino)-A7,Ar-dimethyl-7 / / -pyrrolo[2,3-< / ]pyrimidine-6- carboxamide A153;7-cyclopentyl-2-((5-(4-(4-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- methyl)phenyl)piperazin-l-yl)pyridin-2-yl)amino)-7V,Az-dimethyl-7 / f-pyrrolo[2,3-^]pyrimidine- 6-carboxamide A154;7-cyclopentyl-2-((5-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)cyclohexyl)- piperazin-l-yl)pyridin-2-yl)amino)-A'r,A-dimethyl-7J7-pyrrolo[2,3-tf|pyrimidine-6-carboxamide A155;7-cyclopentyl-2-((5-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperidin-4-yl)- piperazin-l-yl)pyridin-2-yl)amino)-A'jV-dimethyl-77 / -pyrrolo[2,3-t(|pyrimidine-6-carboxamide A156;7-cy clopentyl-2-((5 -(4-( 1 -(2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)ethyl)- piperidin-4-yl)piperazin-l-yl)pyri din-2 -yl)aniino)-7V,7V-dimethy]-7H-pyrrolo[2,3-tf]pyrimidine-6- carboxamide A157:7-cyclopentyl-2-((5-(4-(l-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- methyl)piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-A?,ALdimethyl-7H-pyrrolo[2,3-<^|- pyrimidine-6-carboxamide A158;7-cyclopentyl-2-((5-(4-((r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]- 4-yl)methyl)piperazin-l-yl)pyridin-2-yl)amino)-jV,A'’-dimethyl-7 / / -pyrrolo[2,3-dr]-pyrimidine-6- carboxamide A159;7-cy clopentyl-2-((5 -(4-( 1 -(2-(3 -(2, 6-dioxopiperidin-3 -yl)phenoxy)ethyl)- piperidin-4-yl)piperazin-l-yl)pyri din-2 -yl)amino)-7V,A'r-dimethyl-7 / / -pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A160:7-cyclopentyi-2-((5-(4-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l- yl)propyl)piperazin-l-yl)pyridin-2-yl)amino)-A'^V-dimethyl-7H-pyrrolo[2,3-t(]pyrimidine-6- carboxamide A161;7-cyclopentyl-2-((5-(4-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]- 3-yl)piperazin-l-yl)pyridin-2-yl)amino)-Af,ALdimethyl-777-pyrrolo[2,3-<7]pyrimidine-6- carboxamide A162;7-cyclopentyl-2-((5-(4-(l-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4yl)methyl)piperidin-3-yl)piperazin-l-yl)pyridin-2-yl)amino)-A’,7V-dimethyl-7 / f-pyrrolo[2,3-fiO- pyrimidine-6-carboxamide A163;7-cyclopentyl-2-((5-(4-(l-(((25)-4-(4-(2,6-dioxopiperidin-3-yl)phenyl)- niorpholin-2-yl)methyl)piperidin-4-yl)piperaziii-l-yl)pyridin-2-yl)amiiio)-A7,A^-dimethyl-77f- pyrrolo[2,3-t(|pyrimidine-6-carboxamide A164;7-cyclopentyl-2-((5-(4-(l-(((27?)-4-(4-(2,6-dioxopiperidin-3-yl)phenyl)- morpholin-2-yl)methyl)piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-A’,A7-dimethyl-7J7- pyrrolo[2,3-d]pyrimidine-6-carboxamide A 165;7-cyclopentyl-2-((5-(4-(3-(l-(4-(2,6-dioxopiperidin-3-yl)benzyl)piperidin-4-yl)- cyclohexyl)piperazin-l-yl)pyridin-2-yl)amino)-AAV-dimethyl-777-pyrrolo[2,3-t7]pyrimidine-6- carboxamide A166;7-cyclopentyl-2-((5-(4-(l-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)azetidin-3-yl)- methyl)piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-AT,A7-dimethyl-7Z / -pyrrolo[2,3-<7]- pyrimidine-6-carboxamide A 167;7-cyclopentyl-2-((5-(4-(((25)-4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)morpholiii-2-yl)methyl)piperazin-l-yl)pyridin-2-yl)amino)-A’,Ar-dimethyl-71E / -pyrrolo[2,3- tZ]pyrimidine-6-carboxamide A168;7-cyclopentyl-2-((5-(4-(((2A’)-4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin- 4-yl)morphoHn-2-yl)methyi)piperazin-l-yl)pyridin-2-yl)amino)-Ar,Ar-dimethyl-7 / f-pyrrolo[2,3- c / ]pyrimidine-6-carboxamide A169;7-cyclopentyl-2-((5-(4-((4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- cyclohexyl)methyl)piperazin-l-yl)pyridin-2-yl)amino)-A7,A'-dimethyl-7 / f-pyrrolo[2,3-<7]- pyrimidine-6-carboxamide A170;7-cyclopentyl-2-((5-(4-(2-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l- yl)cyclohexyl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A7-dimethyl-7J7-pyrrolo[2,3-< / ]- pyrimidine-6-carboxamide A171;7-cyclopentyl-2-((5-(4-(l-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l- yl)ethyl)piperidin-4-yl)piperazin-l -yl)pyridin-2-yl)amino)-7V,Ar-dimethyl-7 / 7-pyrrolo[2,3-< / |- pyrimidine-6-carboxamide A172;7-cyclopentyl-2-((5-(4-(4-(2-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4- yl)ethyl)cyclohexyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A-dimethyl-7JH-pyrrolo[2,3-<7]-pyrimidine-6-carboxamide A173;7-cyclopentyl-2-((5-(4-(l-(2-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4- yl)ethyl)piperidin-4-yl)piperazin-l-yl)pyri din-2 -yl)amino)-A?,Ar-dimethyl-7 / 7-pyrrolo[2,3-J|- pyrimidine-6-carboxamide A174;7-cyclopentyl-2-((5-(4-(2-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[4,4'- bipiperi din]- l-yl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-7V,Ar-dimethyl-7JH-pyrrolo[2, 3-J]- pyrirnidine-6-carboxamide A175;7-cyclopentyl-2-((5-(4-(2-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'- bipiperidin]-4-yl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-A^V-dimethyI-7 / / -pyrrolo[2,3-r / ]- pyrimidine-6-carboxamide A176;7-cyclopentyl-2-((5-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethyl)piperazin-l-yl)pyridin-2-yl)amino)-N,N-dimethyl-7 / / -pyrrolo[2,3-J]pyrimidine-6- carboxamide A177;7-cyclopentyl-2-((5-(4-(2-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- ethyl)piperazin-l-yl)pyridin-2-yl)amino)-AVV-dimethyl-7 / f-pyrrolo[2,3-(f|pyrimidine-6- carboxamide A178;7-cyclopentyl-2-((5-(4-(l-(3-(4-(2,6-dioxopiperidin-3-yl)phenoxy)propyl)- piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-Af,Ar-dimethyl-7 / 7-pyrrolo[2,3-<7]pyrimidine-6- carboxamide Al 79;7-cyclopentyi-2-((5-(4-(3-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- propyl)piperazin-l-yl)pyridin-2-yl)amino)-A^,A-dimethyl-777-pyrrolo[2,3-< / ]pyrimidine-6- carboxamide A180;7-cyclopentyl-2-((5-(4-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperidin-4- yl)cyclohexyl)piperazin-l-yl)pyridin-2-yl)amino)-A7,A-dimethyl-7 / f-pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A181;7-cyclopentyl-2-((5-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)-[l,4'-bipiperidin]- r-yl)pyridin-2-yl)amino)-A’,Ar-dimethyl-7 / / -pyrrolo[2,3-r7]pyrimidine-6-carboxamide A182;7-cyclopentyl-2-((5-((r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l ,4'-bipiperidin]-4- yl)methyl)pyridin-2-yl)amino)-Ar,ALdimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide A183;7-cyclopentyl-2-((5-((r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[4,4'-bipiperidin]-lyl)methyl)pyridin-2-yl)amino)-jV,jV-dimethyl-7H-pyrrolo[2,3-<7]pyrimidine-6-carboxamideA184;7-cyclopentyl-2-((5-((4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)methyl)pyridin-2-yl)amino)-A^V-dimethyl-7 / 7-pyrrolo[2,3-tZ]pyrimidine-6- carboxamide Al 85;7-cyclopentyl-2-((5-((l'-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]-4- yl)oxy)pyridin-2-yl)amino)-J¥,A-dimethyl-72 / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide A186;7-cyclopentyl-2-((5-((r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]-4- yl)methoxy)pyridin-2-yl)amino)-7V,jV-dimethyl-72 / -pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A187;7-cyclopentyl-2-((5-(2-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[4,4'-bipiperidin]- l-yl)ethyl)pyridin-2-yl)amino)-A'',J'V-dimethyl-7 / 7-pyrrolo[2,3-^]pyrimidine-6-carboxamide A188;7-cyclopentyl-2-((5-(2-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]- 4-yl)ethyl)pyridin-2-yl)amino)-A^V-dimethyl-777-pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A189;7-cyclopentyl-2-((5-(2-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l -yl)- piperidin-l-yl)ethyl)pyridin-2-yl)amino)-A'r,A-dimetliyl-7 / 7-pyrrolo[2,3-J]pyrimidine-6- carboxamide Al 90;7-cyclopentyi-2-((5-(2-(l'-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[4,4'-bipiperidin]- l-yl)ethoxy)pyridin-2-yl)amino)-Az,A'’-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide A191;7-cyclopentyl-2-((5-(2-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]- 4-yl)ethoxy)pyri din-2 -yl)aniino)-Ar,jV-dimethyl-7 / f-pyrrolo[2,3-<f|pyrimidine-6-carboxaniide A192;7-cyclopentyl-2-((5-(2-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)ethoxy)pyridin-2-yl)amino)-AT,7V-dimethyl-72 / -pyrrolo[2,3-t(]pyrimidine-6- carboxamide Al 93;7-cyclopentyl-2-((5-(4-(l-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- methyl)az.etidin-3-yl)piperazin-l-yl)pyridin-2-yl)amino)-A',A;-dimethyl-7 / / -pyrrolo[2,3-tZ]- pyrimidine-6-carboxamide A194;7-cyclopentyl-2-((5-(4-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]- 4-yl)piperazin- 1 -yllpyri di n-2-y l)amino)-Ar,A-di methy l-77f-pyrrol o[2, 3 -tZ]pyrimidine-6- carboxamide A195;7-cyclopentyl-2-((5-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- [l,4'-bipiperidin]-r-yl)pyridin-2-yl)amino)-7VjV-dimethyl-7H-pyrrolo[2,3-^]pyrimidine-6- carboxamide A196:7-cyclopentyl-2-((5-(4-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- cyclohexyl)piperazin-l-yl)pyridin-2-yl)amino)-A,A-dimethyl-777-pyrrolo[2,3-<7]pyriniidine-6- carboxamide A197;7-cyclopentyl-2-((5-(4-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- cyclohexyl)piperidin-l-yl)pyridin-2-yl)amino)-Al / 7-dimethyl-7 / 7-pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A198;7-cy clopentyl-2-((5 -(4-( 1 -(3 -(3 -(2, 6-dioxopiperi din-3 -yl)phenoxy)propyl)- piperidin-4-yl)piperazin-l-yl)pyri din-2 -yl)amino)-A’,7V-dimethyl-7Ar-pyrrolo[2,3-tf|pyrimidine-6- arboxamide A199;7-cyclopentyl-2-((5-((4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)methyl)pyridin-2-yl)amino)-A,A-dimethyl-7H-pyrrolo[2,3-^pyrimidine-6- carboxamide A200;7-cyclopentyl-2-((5-(2-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)ethyl)pyridin-2-yl)amino)-7V,A’-dimethyl-7 / / -pyrrolo[2,3-( / |pyrimidine-6- carboxamide A201;7-cyclopentyl-2-((5-(3-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[4,4'-bipiperidin]- l-yl)propyl)pyridin-2-yl)amino)-A’,A-diniethyl-7AF-pyrrolo[2,3-Jjpyrimidine-6-carboxamide A202;7-cyclopentyl-2-((5-(3-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)propyl)pyridin-2-yl)amino)-AVV-dimethyl-7 / Z-pyrrolo[2,3-60pyriniidine-6- carboxamide A203;7-cyclopentyl-2-((5-(3-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)propyl)pyridin-2-yl)amino)-A;A'-dimethyl-7JH-pyiTolo[2,3-t / ]pyrimidine-6- carboxamide A204;7-cyclopentyl-2-((5-(3-(r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]4-yl)propyl)pyridin-2-yl)amino)-Ar,A7-dimethyl-7J / -pyrrolo[2,3-t / ]pyrimidine-6-carboxamideA205;7-cyclopentyl-2-((5-(2-(4-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l -yl)- piperidin-l-yl)ethyl)pyridin-2-yl)amino)-A;,A-dimethyl-7JH-pyn'olo[2,3-t / ]pyrimidine-6- carboxamide A206;7-cyclopeiityl-2-((5-((25)-2-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l- yi)methyl)morpholino)pyridin-2-yl)amino)-A7,A'r-dimethyl-7 / / -pyrrolo[2,3<7]pyrimidine-6- carboxamide A207;7-cyclopentyl-2-((5-((27?)-2-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l- yl)methyl)morpholino)pyridin-2-yl)amino)-A’,7V-dimethyl-7H-pyrrolo[2,3-<7]pyrimidine-6- carboxamide A208;7-cyclopentyl-2-((5-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l-yl)- piperidin-l-yl)pyridin-2-yl)amino)-A’,? / -dimethyl-7 / f-pyrrolo[2,3-^pyrimidine-6-carboxamide A209;7-cyclopentyl-2-((5-((r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]-3- yl)oxy)pyridin-2-yl)amino)-A’,Ar-dimethyl-7 / / -pyrrolo[2,3-i / ]pyrimidine-6-carboxamide A210;7-cyclopentyl-2-((5-((3-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)methyl)pyridin-2-yl)amino)-A'’,AT-dimethyl-7 / / -pyrrolo[2,3-<7]pyriniidine-6- carboxamide A211;7-cyclopentyl-2-((5-((r-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[3,4'-bipiperidin]-l- yl)methyl)pyridin-2-yI)amino)-Ar,AAdimethyl-7 / f-pyrrolo[2,3-£Z]pyrimidine-6-carboxamide A212;7-cyclopentyl-2-((5-(2-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)ethoxy)pyridin-2-yl)amino)-Ar,A-dimethyl-7 / f-pyrrolo[2,3-tZ]pyrimidine-6- carboxamide A213;7-cyclopentyl-2-((5-(4-((4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- piperidin-l-yl)methyl)piperidin-l-yl)pyridin-2-yl)amino)-Ar,A7-dimethyl-7J / -pyrrolo[2,3-<f|- pyrimidine-6-carboxamide A214;7-cyclopentyl-2-((5-(4-(4-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- benzyl)piperazin-l-yl)pyridin-2-yl)amino)-A7,A''-dimethyl-7 / / -pyiTolo[2,3-<7]pyrin]idine-6- carboxamide A215;7-cyclopentyl-2-((5-(4-(4-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l -yl)- methyl)phenyl)piperazin-l-yl)pyridin-2-yl)amino)-A’,A'-dimethyl-7I7-pyrrolo[2,3-< / |pyriinidiiie- 6-carboxamide A216,7-cyclopentyl-2-((5-(4-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- methyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A-dimethyl-7 / 7-pyrrolo[2,3-c(]pyrimidine-6- carboxamide A217:7-cyclopentyl-2-((5-(l-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- methyl)piperidin-4-yl)pyridin-2-yl)amino)-ATAr-dimethyl-7 / 7-pyrrolo[2,3-< / ]pyrimidine-6- carboxamide A218;7-cyclopentyl-2-((5-(4-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- methyl)piperidin-l-yl)pyridin-2-yl)amino)-A7,Ar-dimethyl-7 / / -pyrrolo[2,3-^pyrimidine-6- carboxamide A219;7-cyclopentyl-2-((5-(4-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- methyl)piperidin-l-yl)pyri din-2 -yl)amino)-A’,A'r-dimethyl-77 / -pyrrolo[2,3-t(]pyrimidine-6- carboxamide A220:7-cyclopentyl-2-((5-(4-((l-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- methyl)piperazin-l-yl)pyridin-2-yl)amino)-A,A-dimethyl-7H-pyrrolo[2,3-^pyrimidine-6- carboxamide A221;7-cy cl opentyl-2-(( 5 -( 1 -(( 1 -(3 -(2, 6-di oxopiperi din-3 -yl )phenyl)piperi din-4-y I )- methyl)piperidin-4-yl)pyridin-2-yl)amino)-A7,Ar-dimethyl-77 / -pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A222;7-cyclopentyl-2-((5-(4-((4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- methyl)piperidin-l-yl)pyri din-2 -yl)amino)-A',A'r-dimethyl-777r-pyrrolo[2,3-tf|pyrimidine-6- carboxamide A223:7-cyclopentyl-2-((5-(4-((4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- methyl)piperidin-l-yl)pyridin-2-yl)amino)-? / ,7V-dimethyl-7 / Z-pyrrolo[2,3-^pyrimidine-6- carboxamide A224;7-cyclopentyl-2-((5-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]-r- yl)methyl)pyridin-2-yl)amino)-A,A-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide A225;7-cyclopentyl-2-((5-(4-(2-(4-(4-(2, 6-dioxopiperidin-3-yl)phenyl)piperi din-1 -yl)-ethyl)piperazin-l-yl)pyridin-2-yl)amino)W,? / -dimethyl-7H-pyrrolo[2,3-(7]pyrimidine-6- carboxamide A226;7-cyclopentyl-2-((5-(l-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- ethyl)piperidin-4-yl)pyridin-2-yl)amino)-A;,A-dimethyl-7JH-pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A227;7-cy cl opentyl-2-((5 -( 1 -(2-(4-(4-(2, 6-dioxopiperi din-3 -yl)pheny l)piperazin- 1 -yl)- ethyl)piperidin-4-yl)pyridin-2-yl)amino)-A / 7-dimethyl-7#-pyrrolo[2,3-6f]pyrimidine-6- carboxamide A228;7-cyclopentyl-2-((5-( 1 -(2-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin- 1 -yl)- ethyl)piperidin-4-yl)pyridin-2-yl)amino)-A,A-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6- carboxamide A229;7-cyclopentyl-2-((5-(4-(2-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A7-dimethyl-7 / / -pyrrolo[2,3-^pyrimidine-6- carboxamide A 230:7-cy clopentyl-2-((5 -(4-(2-( 1 -(3 -(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- ethyl)piperazin-l-yl)pyridin-2-yl)amino)-AT,A'-dimethyl-7 / / -pyrrolo[2,3-( / |pyrimidine-6- carboxamide A231;7-cyclopentyl-2-((5-(4-(2-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A-dimethyl-7 / 7-pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A232:7-cyclopentyl-2-((5-(l-(2-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethyl)piperidin-4-yl)pyridin-2-yl)amino)-A,A-dimethyl-7JH-pyrrolo[2,3-t / ]pyrimidine-6- carb oxami de A233;7-cy cl opentyl-2-((5 -( 1 -(2-( 1 -(3 -(2, 6-dioxopiperi din-3 -yl)pheny l)piperi din-4-yl)- ethyl)piperidin-4-yl)pyridin-2-yl)amino)-Ar,A-dimethyl-72 / -pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A234;7-cyclopentyl-2-((5-( 1 -(2-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin- 1 -yl)- ethyl)piperidin-4-yl)pyridin-2-yl)amino)-A,A-dimethyl-7H-pyrrolo[2,3-t7]pyrimidine-6- carboxamide A235;7-cyclopentyl-2-((5-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]- r-yl)ethyl)pyridin-2-yl)amino)-Ar,AT-dimethyl-77f-pyrrolo[2,3-r / ]pyrimidine-6-carboxamideA236;7-cyclopentyl-2-((5-(r-(4-(2,6-dioxopiperidin-3-yl)phenethyl)-[4,4'-bipiperidin]- l-yl)pyridin-2-yl)amino)-A,A-dimethyl-7Z / -pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A237;7-cyclopentyl-2-((5-(r-(4-(2,6-dioxopiperidin-3-yl)phenethyl)-[l,4'-bipiperidin]- 4-yl)pyridin-2-yl)amino)-A,Ar-dimethyl-7 / / -pyrrolo[2,3-t(|pyrimidine-6-carboxamide A238;7-cy clopentyl-2-((5 -(2-(4-( 1 -(3 -(2, 6-dioxopiperi din-3 -yl)pheny l)pi p eri di n-4 -y 1 )- piperazin-l -yl)ethyl)pyridin-2-yl)amino)-A’,7V-dimethyl-7 / / -pyrrolo[2,3-6Z]pyrimidine-6- carboxamide A239;7-cyclopentyl-2-((5-(2-(l'-(3-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]- 4-yl)ethyl)pyridin-2-yl)amino)-A,JV-dimethyl-7 / / -pyrrolo[2;3-<7]pyrimidine-6-carboxamide A240;7-cyclopentyl-2-((5-(2-(r-(3-(2,6-dioxopiperidin-3-yl)phenyl)-[4,4'-bipiperidin]- l-yl)ethyl)pyridin-2-yl)amino)-Ap\Mimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide A241;7-cyclopentyl-2-((5-(2-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]- r-yl)ethyl)pyridin-2-yl)amino)-Az^V-dimethyl-7 / 7-pyrrolo[2,3-tZ]pyrimidine-6-carboxamide A242;7-cyclopentyl-2-((5-(2-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)ethoxy)pyridin-2-yl)amino)-A7V-dimethyl-7 / / -pyrrolo[2,3-<7]pyriniidine-6- carboxamide A243;7-cyclopentyl-2-((5-(2-(4-(l-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)ethoxy)pyridin-2-yl)amino)-AAV-dimethyl-7J7-pyrrolo[2,3-^pyrimidine-6- carboxamide A244;7-cyclopentyl-Ar,A-dimethyl-2-((5-(4-(l-(4-(3-methyl-2,6-dioxopiperidin-3-yl)- phenethyl)piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-7 / / -pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A245;7-cyclopentyl-2-((5-(4-(2-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- ethyl)piperidin-l-yl)pyridin-2-yl)amino)-A,A-dimethyl-7H-pyrrolo[2,3-< / ]pyrimidine-6- carboxamide A246;7-cyclopentyl-2-((5-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethyl)piperidin-l-yl)pyridin-2-yl)amino)-Air,A-dimethyl-7Jff-pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A247;7-cyclopentyl-2-((5-(4-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- ethy l)piperi din- 1 -yl)pyri din-2 -yl)amino)-AT, A-dimethy I -7 / 7-pyrrol o [2, 3 -tfjpyrimi dine-6- carboxamide A248;7-cyclopentyl-2-((5-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- propoxy)pyridin-2-yl)amino)-AA,iV-dimethyl-7 / f-pyrrolo[2,3-<7]pyrimidine-6-carboxamide A249;7-cyclopentyl-2-((5-(3-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- propoxy)pyridin-2-yl)amino)-Ar,Ar-dimethyl-7 / 7-pyrrolo[2,3-(7]pyrimidine-6-carboxamide A250;7-cyclopentyl-2-((5-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- ethoxy)pyridin-2-yl)amino)-Ar,A-dimethyl-777-pyrrolo[2,3-tf|pyrimidine-6-carboxamide A251;7-cyclopentyl-2-((5-(2-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- ethoxy)pyridin-2-yl)amino)- / V,7V-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide A252;7-cyclopentyl-2-((5-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)-4-fluoro-[l,4'- bipiperidin]-r-yl)pyridin-2-yl)amino)-A^V-dimethyl-72 / -pyrrolo[2,3-i(]pyrimidine-6- carboxamide A253:7-cyclopentyl-2-((5-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)pyridin-2-yl)amino)-V,A-dimethyl-7J7-pyrrolo[2,3-<7]pyrimidine-6-carboxamide A254;7-cyclopentyl-2-((5-(4-(l-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)- piperazin-l-yl)pyridin-2-yl)amino)-AjV-dimethyl-7 / / -pyrrolo[2,3-t(|pyrimidine-6-carboxaniide A255;7-cyclopentyl-2-((5-(4-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)azetidin-3-yl)- methyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,Ar-dimethyl-777-pyrrolo[2,3-tflpyrimidine-6- carboxamide A256:7-cyclopentyi-2-((5-(4-((l-(3-(2,6-dioxopiperidin-3-yl)phenyl)azetidin-3-yl)- methyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A7-dimethyl-7Z / -pyrrolo[2,3-(7]pyrimidine-6- carboxamide A257;7-cyclopentyl-2-((5-(4-(2-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)azetidin-3-yl)- ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar7V-dimethyl-7J7-pyrrolo[2,3-<7]pyrimidine-6- carboxamide A258;7-cy clopenty!-2-((5 -(4-(2-( 1 -(3 -(2, 6-dioxopiperidin-3 -yljpheny l)azetidin-3 -yl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-A,A-dimethyl-7H-pyrrolo[2,3-(7]pyrimidine-6- carboxamide A259;7-cyclopentyl-2-((5-(4-(l-(2-(4-(2,6-dioxopiperidin-3-yl)phenyl)-2,2-difluoro- ethyl)piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,AMimethyl-7 / / -pyrrolo[2,3-d]- pyrimidine-6-carboxamide A260;7-cyclopentyl-2-((5-(4-(l-(2-(3-(2,6-dioxopiperidin-3-yl)phenyl)-2,2-difluoro- ethyl)piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-A',7V-dimethyl-7 / / -pyrrolo[2,3-cfj- pyrimidine-6-carboxamide A261;7-cyclopentyl-2-((5-(4-(l-(2-(4-(2,6-dioxopiperidin-3-yl)phenyl)-2,2-difluoro- ethyl)azetidin-3-yl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,JV-dimethyl-777-pyrrolo[2,3-t(|- pyrimidine-6-carboxamide A262;7-cyclopentyl-2-((5-(4-(l-(2-(3-(2,6-dioxopiperidin-3-yl)phenyl)-2,2-difluoro- ethyl)azetidin-3-yl)piperazin-l-yl)pyridin-2-yl)amino)-A,A’-dimethyl-77 / -pyrrolo[2,3-t / ]- pyrimidine-6-carboxamide A263;7-cyclopentyl-2-((5-(4-(l-(4-(2,6-dioxopiperidin-3-yl)benzyl)azetidin-3-yl)- piperazin-l-yl)pyridin-2-yl)amino)-AjV-dimethyl-77 / -pyrrolo[2,3-i(|pyrimidine-6-carboxaniide A264;7-cyclopentyl-2-((5-(4-(l-(3-(2,6-dioxopiperidin-3-yl)benzyl)azetidin-3-yl)- piperazin-l-yl)pyridin-2-yl)amino)-A,A-dimethyl-7 / 7-pyrrolo[2,3-< / ]pyrimidine-6-carboxamide A265;7-cyclopentyl-2-((5-(4-(3-(2,6-dioxopiperidin-3-yl)phenethyl)-4-fluoro-[l,4'- bipiperidin]-r-yl)pyridin-2-yl)amino)-A,Ar-dimethyl-7 / f-pyrrolo[2,3-t(]pyrimidine-6- carboxamide A266;7-cyclopentyl-2-((5-(4-(4-(2,6-dioxopiperidin-3-yl)benzyl)-4-fluoro-[l,4'- bipiperidin]-r-yl)pyridin-2-yl)amino)-A^V-dimethyl-7 / Apyrrolo[2,3-tZ]pyrimidine-6- carboxamide A267;7-cyclopentyl-2-((5-(4-(3-(2,6-dioxopiperidin-3-yl)benzyl)-4-fluoro-[l,4'- bipiperidin]-T-yl)pyridin-2-yl)amino)-A^V-dimethyl-777-pyrrolo[2,3-tZ]pyrimidine-6- carboxamide A268;7-cyclopentyl-2-((5-(4-(3-(4-(2,6-dioxopiperidin-3-yl)phenethyl)-3-fluoro- azetidin-l-yl)piperidiii-l-yl)pyridin-2-yl)aniiiio)-Ar,A7-dimethyl-7i7-pyrrolo[2,3-^]pyrimidine-6-carboxamide A269;7-cyclopentyl-2-((5-(4-(3-(3-(2,6-dioxopiperidin-3-yl)phenethyl)-3-fluoro- azeti din-1 -yl)piperidin-l-yl)pyridin-2-yl)amino)-A’,Ar-dimethyl-7Z7-pyrrolo[2,3-J|pyrimidine-6- carboxamide A270;7-cyclopentyl-2-((5-(3-(l-(2-(4-(2,6-dioxopiperidin-3-yl)phenyl)-2,2-difluoro— ethyl)piperidin-4-yl)azetidin-l-yl)pyridin-2-yl)amino)-A,A-dimethyl-7 / / -pyrrolo[2,3-t / ]- py rimidine-6-carboxamide A271 ;7-cyclopentyl-2-((5-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l-yl)- azetidin-l-yl)pyridin-2-yl)amino)-Ar,A7-dimethyl-7J / -pyrrolo[2,3-( / ]pyrimidine-6-carboxamide A272;7-cyclopentyl-2-((5-(3-(4-(3-(2,6-dioxopiperidin-3-yl)phenethyl)piperazin-l-yl)- azetidin-l-yl)pyridin-2-yl)amino)-A,A'-dimethyl-7Ar-pyrrolo[2,3-(7]pyrimidine-6-carboxamide A273;7-cyclopentyl-2-((5-(3-(4-(4-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yl)- azetidin-l-yl)pyridin-2-yl)amino)-A,A-dimethyl-77 / -pyrrolo[2,3-(7]pyrimidine-6-carboxamide A274;7-cyclopentyl-2-((5-(3-(4-(3-(2,6-dioxopiperidin-3-yl)benzyl)piperazin-l-yl)- azetidiii-l-yl)pyridin-2-yl)aniino)-Ar,A7-dimethyl-7J / -pyrrolo[2,3-c(|pyrimidine-6-carboxamide A275;7-cyclopentyi-2-((5-(4-(3-(4-(2,6-dioxopiperidin-3-yl)benzyl)-3-fluoroazetidin-l- yl)piperidin-l-yl)pyridin-2-yl)amino)-A’,A'r-dimethyl-7 / 7-pyrrolo[2,3-tf|pyrimidine-6- carboxamide A276;7-cyclopentyl-2-((5-(4-(3-(3-(2,6-dioxopiperidin-3-yl)benzyl)-3-fluoroazetidin-l- yl)piperidin-l-yl)pyridin-2-yl)amino)-Af,Ar-dimethyl-7 / ?-pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A277;7-cyclopentyl-2-((5-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)piperidin-l-yl)- azetidin-l-yl)pyridin-2-yl)amino)-AT,A'-dimethyl-7J / -pyrrolo[2,3-<f|pyrimidine-6-carboxamide A278;7-cyclopentyl-2-((5-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenethyl)-4-fluoro- piperidin-l-yl)azetidin-l-yl)pyridin-2-yl)amino)-A,A-dimethyl-77 / -pyrrolo[2,3-< / ]pyrimidine-6- carboxamide A279;7-cy cl opentyl-2-((5 -(3 -(4-(3 -(2, 6-di oxopiperi din-3 -y 1 )phenethyl)piperidin- 1 -yl)- azetidin-l-yl)pyridin-2-yl)amino)-A,A-dimethyl-7Ar-pyrrolo[2,3-<7|pyrimidine-6-carboxamide A280;7-cyclopentyl-2-((5-(3-(4-(3-(2,6-dioxopiperidin-3-yl)phenethyl)-4-fluoro- piperidin-l-yl)azetidin-l-yl)pyridin-2-yl)amino)-Ar,A’-dimethyl-7 / / -pyrrolo[2,3-<^]pyrimidine-6- carboxamide A281:7-cyclopentyl-2-((5-(3-(4-(3-(2,6-dioxopiperidin-3-yl)benzyl)-4-fluoropiperidin- l-yl)azetidin-l-yl)pyridin-2-yl)amino)-A',7V-dimethyl-7 / 7-pyrrolo[2,3-< / jpyrimidine-6- carboxamide A282;7-cyclopentyl-2-((5-(3-(4-(4-(2,6-dioxopiperidin-3-yl)benzyl)-4-fluoropiperidin-1 -yl)azetidin- 1 -yl)pyridin-2-yl)amino)-A)A-dimethyl-7 / / -pyrrolo[2,3 -t / ]pyrimidine-6- carboxamide A283;7-cyclopentyl-2-((5-(4-((3-(4-(2,6-dioxopiperidin-3-yl)phenyl)azetidin-l-yl)- methyl)-4-fluoropiperidin-l-yl)pyridin-2-yl)amino)-A?’,A-dimethyl-77 / -pyrrolo[2,3-'^]pyrin]idine- 6-carboxamide A284;7-cyclopentyl-2-((5-(4-((3-(3-(2,6-dioxopiperidin-3-yl)phenyl)azetidin-l-yl)- methyl)-4-fluoropiperidin-l-yl)pyridin-2-yl)amino)-AAV-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine- 6-carboxamide A285;7-cy cl opentyl-2-(( 5 -( 1 -(( 1 -(3 -(2, 6-di oxopiperi din-3 -yl )phenyl)-4-fluoropiperi din- 4-yl)methyl)piperidin-4-yl)pyridin-2-yl)amino)-A,Ar-dimethyl-7jE / -pyrrolo[2,3-d]pyrimidine-6- carboxamide A286;7-cyclopentyl-2-((5-(l-((l-(4-(2,6-dioxopiperidin-3-yl)phenyl)-4-fluoropiperidin- 4-yl)methyl)piperidin-4-yl)pyridin-2-yl)amino)-A'',yV-dimethyl-7Ar-pyiTolo[2,3-J]pyrimidine-6- carboxamide A287:7-cyclopentyl-2-((5-(4-((4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- methyl)-4-fluoropiperidin-l-yl)pyridin-2-yl)amino)-AJ\Mimethyl-7H-pyrrolo[2,3-d]pyrimidine- 6-carboxamide A288;7-cyclopentyl-2-((5-(4-((4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- methyl)-4-fluoropiperidin-l-yl)pyri din-2 -yl)amino)-ArALdimethyl-7JH-pyrrolo[2,3-tZ]pyrimidine- 6-carboxamide A289,7-cy cl opentyl-2-((5 -(4-(2-( 1 -(4-(2, 6-di oxopiperi din-3 -yl)-3 -fluorophenyl)-piperidin-4-yl)ethyl)piperazin-l -yl)pyridin-2-yl)amino)-Ar,A’-dimethyl-7 / 7-pyrrolo[2,3-<7]- pyrimidine-6-carboxamide A290;7-cyclopentyl-2-((5-(4-(2-(l-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)- piperidin-4-yl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,ALdimethyl-7 / / -pyrrolo[2,3-d]- pyrimidine-6-carboxamide A291 ;2-((5-(4-(2-(l-(3-chloro-4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)ethyl)- piperazin-l-yl)pyridin-2-yl)amino)-7-cyclopentyl-Az,A-dimethyl-7 / / -pyrrolo[2,3-< / ]pyrimidine-6- carboxamide A292;2-((5-(4-(2-(l-(2-chloro-4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)ethyl)- piperazin-l-yl)pyridin-2-yl)amino)-7-cyclopentyl-A7,A-dimethyl-777-pyrrolo[2,3-tZ]pyrimidine-6- carboxamide A293;7-cyclopentyl-2-((5-(3-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- azetidin"l-yl)pyridin-2-yl)amino)-Ar,A7-dimethyl-77f-pyrrolo[2,3-^pyrimidine-6-carboxamide A294;7-cyclopentyl-2-((5-(4-(l-(4-(2,6-dioxopiperidin-3-yl)phenyl)azetidin-3-yl)- piperazin-l-yl)pyridin-2-yl)amino)-AjV-dimethyl-77 / -pyrrolo[2,3-i(|pyrimidine-6-carboxamide A295;7-cyclopentyl-2-((5-(3-(4-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-l-yl)- azetidin-l-yl)pyridin-2-yl)amino)-A7,ALdimethyl-777-pyrrolo[2,3-c / ]pyrimidine-6-carboxamide A296;7-cyclopentyl-2-((5-(4-(2-(l-(3-(2,6-dioxopiperidin-3-yl)-5-fluorophenyl)- piperidin-4-yl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A7-dimethyl-7 / 7-pyrrolo[2,3-c / ]- pyrimidine-6-carboxamide A297;7-cyclopentyl-2-((5-(4-(2-(l-(3-(2,6-dioxopiperidin-3-yl)-4-fluorophenyl)- piperidin-4-yl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar / / -dimethyl-7Z / -pyrrolo[2,3-< / ]- pyrimidine-6-carboxamide A298;7-cyclopentyl-2-((5-(4-(4-(2,6-dioxopiperidin-3-yl)-3-fluorophenethyl)-4-fluoro- [l,4'-bipiperidin]-r-yl)pyridin-2-yl)amino)-Ar,Ar-dimethyl-7J7-pyrrolo[2,3-tf|pyrimidine-6- carboxamide A299;7-cyclopentyl-2-((5-((r-(3-(2,6-dioxopiperidin-3-yl)phenyl)-[l,4'-bipiperidin]-4- yl)methoxy)pyridin-2-yl)amino)-Ar,AMimethyl-7 / / -pyrrolo[2,3-tZ]pyrimidine-6-carboxamideA300;7-cyclopentyl-2-((5-(3-(2-(4-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-l-yl)- l,l-difluoroethyl)azetidin-l-yl)pyridin-2-yl)amino)-A,ALdimethyl-777-pyrrolo[2,3-t / ]pyrimidine- 6-carboxamide A351;7-cyclopentyl-2-((5-(4-(2-(l-(5-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)~ piperidin-4-yl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-A,A7-dimethyl-77 / -pyrrolo[2,3-t / ]- pyrimidine-6-carboxamide A352;7-cyclopentyl-2-((5-(4-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenethyl)-4-fluoro- [l,4'-bipiperidin]-r-yl)pyridin-2-yl)amino)-ArpV-dimethyl-777-pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A353;7-cyclopentyi-2-((4-((2-(4-(2-(3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)- phenoxy)acetyl)piperazin-l-yl)ethyl)carbamoyl)phenyl)amino)-A / ,A7-dimethyl-7J7-pyrrolo[2,3-6f]- pyrimidine-6-carboxamide A401;7-cyclopentyl-2-((4-((4-(4-(2-(3-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)- phenoxy)acetyl)piperazin-l-yl)butyl)carbamoyl)phenyl)amino)-A’,ALdimethyl-7 / / -pyrrolo[2,3- t / ]pyrimidine-6-carboxamide A402;7-cyclopentyl-2-((4-((6-(4-(2-(3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)- phenoxy)acetyl)piperazin-l-yl)hexyl)carbamoyl)phenyl)amino)-Az,Ar-dimethyl-7 / 7-pyrrolo[2,3- tZ]pyrimidine-6-carboxamide A403;7-cyclopentyi-2-((4-((2-(4-(2-(4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)- phenoxy)acetyl)piperazin-l-yl)ethyl)carbamoyl)phenyl)amino)-A / ,A;-dimethyl-7Ar-pyrrolo[2,3-J]- pyrimidine-6-carboxamide A404;7-cyclopentyl-2-((4-((4-(4-(2-(4-(2,4-dioxotetrahydropyrimidin-l(2 / A)-yl)- phenoxy)acetyl)piperazin-l-yl)butyl)carbamoyl)phenyl)aniino)-A7,A7-dimethyl-7 / f-pyrrolo[2,3- t / ]pyrimidine-6-carboxamide A405;7-cyclopentyl-2-((4-((6-(4-(2-(4-(2,4-dioxotetrahydropvrimidin-l(2 / / )-yl)- phenoxy)acetyl)piperazin-l-yl)hexyl)carbamoyl)phenyl)amino)-Az,Ar-dimethyl-7 / f-pyrrolo[2,3- <7]pyrimidine-6-carboxamide A406;7-cyclopentyl-2-((4-(4-(3-(2,4-dioxotetrahydropyrimidin-l(2Z7)-yl)phenyl)- piperazin-l-yl)phenyl)amino)-Ar,A’-dimethyl-77 / -pyrrolo[2,3-< / ]pyriniidine-6-carboxamide A407;7-cyclopentyl-2-((5-(4-(4-(2,4-dioxotetrahydropyrimidin-l(2Z / )-yl)phenyl)-piperazin-l-yl)pyridin-2-yl)amino)-Ar,A’-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6-carboxamideA408;7-cyclopentyl-2-((4-(4-(4-(2,4-dioxotetrahydropyrimidin-l(2H)-yl)benzyl)- piperazin- 1 -yl)phenyl)amino)-7Z,A7-dimethyl-7 / Z-pyrrolo[2,3 -t / ]pyrimidine-6-carboxamide A409;7-cyclopentyl-2-((4-(4-(4-(2,4-dioxotetrahydropyrimidin-l(2Z / )-yl)phenethyl)- piperazin-l-yl)phenyl)amino)-A^V-dimethyl-7 / 7-pyrrolo[2,3-t7]pyrimidine-6-carboxamide A410;7-cyclopentyl-2-((5-(4-(2-(4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenoxy)- ethyl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A7-dimethyl-7 / 7-pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A411;7-cyclopentyl-2-((4-(2-(4-(4-(2,4-dioxotetrahydropyrimidin-l(277)-yl)phenyl)- piperazin-l-yl)ethyl)phenyl)amino)-Ar,Ar-dimetliyl-7Ar-pyrrolo[2,3-(7]pyrimidine-6-carboxamide A412;7-cyclopentyl-2-((4-(2-(4-(3-(2,4-dioxotetrahydropyrimidin-l(2 / Z)-yl)phenyl)- piperazin-l-yl)ethyl)phenyl)amino)-Afr,A’-dimethyl-7H-pyrrolo[2,3-i(|pyrirnidine-6-carboxamide A413;7-cyclopentyl-2-((5-((4-(4-(2,4-dioxotetrahydropyrimidin-l(27 / )-yl)phenyl)- piperazin-l-yl)methyl)pyridin-2-yl)amino)-A,ALdimethyl-7H-pyrrolo[2,3-^pyrimidine-6- carboxamide A414;7-cyclopentyl-2-((5-(2-(4-(4-(2,4-dioxotetrahydropyrimidin-l(27 / )-yl)phenyl)- piperaziii-l-yl)ethoxy)pyridin-2-yl)amiiio)-Ar,A7-diniethyl-7 / / -pyrrolo[2,3-c(|pyrimidine-6- carboxamide A415;7-cyclopentyl-2-((4-(2-(4-(4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenyl)- piperazin-l-yl)ethoxy)phenyl)amino)-A',A7-dimethyl-7 / 7-pyiTolo[2,3-J]pyrimidine-6- carboxamide A416:7-cyclopentyi-2-((4-(2-(4-(3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenyl)- piperazin-l-yl)ethoxy)phenyl)amino)-A,AMimethyl-7 / / -pyrrolo[2,3-tZ]pyrimidine-6- carboxamide A417;7-cyclopentyl-2-((4-(2-(4-(4-(2,4-dioxotetrahydropyrimidin-l(27 / )-yl)benzyl)- piperazin-l-yl)ethoxy)phenyl)amino)-A7A-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine-6- carboxamide A418;7-cyclopentyl-2-((5-((4-(3-(2,4-dioxotetrahydropyrimidin-l(217)-yl)phenyl)-piperazin- 1 -yl)methyl)pyridin-2-yl)amino)-A; A'-dimethy I -7 / 7-pyrrol o [2, 3 -<7]pyrimi dine-6- carboxamide A419;7-cyclopentyl-2-((4-(4-(l-(4-(2,4-dioxotetrahydropyrimidin-l(22 / )-yl)phenyl)- piperidin-4-yl)piperazin-l-yl)phenyl)amino)-Ar,Ar-dimethyl-7 / f-pyrrolo[2,3-^pyrimidine-6- carboxamide A420;7-cyclopentyl-2-((4-(4-(l-(3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenyl)- piperidin-4-yl)piperazin-l-yl)phenyl)amino)- / V,A-dimethyl-7Ar-pyrrolo[2,3-<7Jpyrimidine-6- carboxamide A421;7-cyclopentyl-2-((4-(2-(4-(4-(2,4-dioxotetrahydropyrimidin-l(22 / )-yl)benzyl)- piperazin-l-yl)ethyl)phenyl)amino)-Ar,A'-dimethyl-7 / 7-pyrrolo[2,3-tf|pyrimidine-6-carboxamide A422;7-cyclopentyl-2-((4-(2-(4-(3-(2,4-dioxotetrahydropyrimidin-l(2#)-yl)benzyl)- piperazin-l-yl)ethyl)phenyl)amino)-Ar,AMimethyl-7 / / -pyrrolo[2,3-d]pyrimidine-6-carboxamide A423;7-cyclopentyl-2-((4-(2-(4-(3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)benzyl)- piperaziii-l-yl)ethoxy)phenyl)amino)-Ar,Ar-dimethyl-7 / 7-pyrrolo[2,3-i / ]pyrimidine-6- carboxamide A424;7-cyclopentyl-2-((4-(2-(4-(4-(4-(2,4-dioxotetrahydropyrimidin-l(27 / )-yl)phenyl)- piperazin-l-yl)piperidin-l-yl)ethyl)phenyl)amino)-A’,7V-dimethyl-77 / -pyrrolo[2,3-t / ]pyrimidine- 6-carboxamide A425;7-cyclopentyl-2-((4-(2-(4-(4-(3-(2,4-dioxotetrahydropyrimidin-l(27 / )-yl)phenyl)- piperazin-l-yl)piperidin-l-yl)ethyl)phenyl)amino)-A,A7-dimethyl-7Z / -pyrrolo[2,3-<7]pyrimidine- 6-carboxamide A426;7-cyclopentyl-2-((4-(2-(4-(4-(4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenyl)- piperazin-l-yl)piperidin-l-yl)ethoxy)phenyl)amino)-7V,Az-dimethyl-7 / / -pyrrolo[2,3-<7]pyrimidine- 6-carboxamide A427,7-cyclopentyl-2-((4-(4-(l-(4-(2,4-dioxotetrahydropyrimidin-l(2Jc / )-yl)phenethyl)- piperidin-4-yl)piperazin-l-yl)phenyl)amino)-A,A-dimethyl-7J7-pyrrolo[2,3-<7]pyrimidine-6- carboxamide A428;7-cyclopentyl-2-((4-(4-( 1 -(3-(2,4-dioxotetrahydropyrimidin- 1 (2 / / )-yl)phenethyl)- piperidin-4-yl)piperazin-l-yl)phenyl)amino)-A^-dimethyl-7 / Z-pyrrolo[2,3-<7]pyrimidine-6-carboxamide A429;7-cyclopentyl-2-((5-(4-( 1 -(4-(2,4-dioxotetrahydropyrimidin- 1 (2 / 7)-yl)benzyl)- piperidin-4-yl)piperazin-l -yl)pyridin-2-yl)amino)-A,ALdimethyl-7 / 7-pyrrolo[2,3-<7]pyrimidine-6- carboxamide A430;7-cyclopentyl-2-((4-(4-((l-(4-(2,4-dioxotetrahydropyrimidin-l(2Z / )-yl)phenyl)- piperidin-4-yl)methyl)piperazin-l-yl)phenyl)amino)-A7,A7-dimethyl-7J / -pyrrolo[2,3-t / ]pyrimidine- 6-carboxamide A431;7-cyclopentyl-2-((4-(4-((l-(3-(2,4-dioxotetrahydropyrimidin-l (2 / 7)-yl)phenyl)- piperidin-4-yl)methyl)piperazin-l-yl)phenyl)amino)-A’,A’-dimethyl-7Z / -pyrrolo[2,3-^pyrimidine- 6-carboxamide A432;7-cyclopentyi-2-((4-(4-(2-(4-(4-(2,4-dioxotetrahydropyrimidin-l(27 / )-yl)phenyl)- piperidin-l-yl)ethyl)piperazin-l-yl)phenyl)amino)-A7,A'r-dimethyl-7 / / -pyrrolo[2,3<(|pyrimidine- 6-carboxamide A433;7-cyclopentyl-2-((4-(4-(2-(4-(3-(2,4-dioxotetrahydropyrimidin-l(277)-yl)phenyl)- piperidin- 1 -yl)ethyl)piperazin- 1 -yl)phenyl)amino)-A,AMimethyl-7 / / -pyrrolo[2,3 -t / ]pyrimidine- 6-carboxamide A434, 7-cyclopentyl-2-((5-(4-(l-(4-(2,4-dioxotetrahydropyrimidin-l(22 / )-yl)phenethyl)- piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-A’,Ar-dimethyl-7 / / -pyrrolo[2,3-< / ]pyrimidine-6- carboxamide A435;2-((5-(4-(2-(l-(3-chloro-4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenyl)- piperidin-4-yl)ethyl)piperazin-l-yl)pyridin-2-yl)amino)-7-cyclopentyl-Ar,A’-dimethyl-7 / / - pyrrolo[2,3-c(]pyrimidine-6-carboxamide A436;7-cyclopentyl-2-((5-(4-((l-(4-(2,4-dioxotetrahydropyrimidin-l(27 / )-yl)phenyl)- piperidin-4-yl)methyl)piperazin-l-yl)pyridin-2-yl)amino)-Af,Ar-dimethyl-7 / f-pyrrolo[2,3-t / ]- pyrimidine-6-carboxamide A437;2-((5-(4-((l -(3 -chloro-4-(2,4-dioxotetrahydropyrimidin- 1 (2H)-yl)phenyl)- piperidin-4-yl)methyl)piperazin-l-yl)pyridin-2-yl)amino)-7-cyclopentyl-Ar,Ar-dimethyl-7Zf- pyrrol o[2, 3 -<7]pyrimidine-6-carboxamide A438;7-cyclopentyl-2-((5-(4-(l-(4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenyl)- piperidin-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-Ar,A’-dimethyl-72 / -pyrrolo[2,3-<7]pyrimidine-6- carboxamide A439;2-((5-(4-(l-(2-(3-chloro-4-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)phenyl)-2,2- difluoroethyl)piperidiii-4-yl)piperazin-l-yl)pyridin-2-yl)amino)-7-cyclopentyl-Ar,A7-dimethyl-7 / f- pyrrolo[2,3-tf]pyrimidine-6-carboxamide A440;7-cyclopentyl-2-((4-((2-(4-(2-((3-(2,6-dioxopiperidin-3-yl)-l-methyl-l / / -indazol-7-yl)oxy)acetyl)piperazin-l-yl)ethyl)carbamoyl)phenyl)amino)-AAV-dimethyl-7H-pyrrolo[2,3-i / j- pyrimidine-6-carboxamide A501;7-cyclopentyl-2-((4-((4-(4-(2-((3-(2,6-dioxopiperidin-3-yl)-l-methyl-l / / -indazol- 7-yl)oxy)acely4)piperazin-l-yl)butyl)carbamoyl)phenyl)amino)-A,A’-dimethyl-7 / / -pyrrolo[2,3- tZjpyrimidine-6-carboxamide A502;7-cyclopentyl-2-((4-((6-(4-(2-((3-(2,6-dioxopiperidin-3-yl)-l-methyl-l / 7-indazol- 7-yl)oxy)acety'l)piperazin-l-yl)hexyl)carbamoyl)phenyl)amino)-jV,Ar-dimethyl-72 / -pyrrolo[2,3- <7]pyrimidine-6-carboxamide A503;7-cyclopentyl-2-((4-((2-(4-(2-((3-(2,6-dioxopiperidin-3-yl)-l-methyl-lZ7-indazol- 6-yl)oxy)acetyl)piperazin-l-yl)ethyl)carbamoyl)phenyl)amino)-Az,A-dimethyl-7H-pyrrolo[2,3-^]- pyrimidine-6-carboxamide A504;7-cyclopentyl-2-((4-((4-(4-(2-((3-(2,6-dioxopiperidin-3-yl)-l-methyl-l / 7-indazol- 6-yl)oxy)acetyl)piperazin-l-yl)butyl)carbamoyl)phenyl)amino)-A,A7-dimethyl-7 / / -pyrrolo[2,3- Jjpyrimidine-6-carboxamide A505;7-cyclopentyl-2-((4-((6-(4-(2-((3-(2,6-dioxopiperidin-3-yl)-l-methyl-l / / -indazol- 6-yl)oxy)acetyl)piperazin-l-yl)hexyl)carbamoyl)phenyl)amino)-jV,?7-dimethyl-72 / -pyrrolo[2,3- d]pyrimidine-6-carboxamide A506;7-cyclopentyl-2-((4-((2-(4-(2-((3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)-l- methyl- l / / -indazol-7-yl)oxy)acetyl)piperazin- 1 -yl)ethyl)carbamoyl)phenyl)amino)-jV,A- dimethyl-7Jff-pyrrolo[2,3-^pyrimidine-6-carboxamide A551;7-cyclopentyl-2-((4-((4-(4-(2-((3 -(2,4-dioxotetrahydropyrimidin- 1 (27 / )-y 1)- 1 - methyl- l / / -indazol-7-yl)oxy)acetyl)piperazin- 1 -yl)butyl)carbamoyl)phenyl)amino)-A, A7- dimethyl-7J / -pyrrolo[2,3-tZ]pyrimidine-6-carboxamide A552;7-cyclopentyl-2-((4-((6-(4-(2-((3-(2,4-dioxotetrahydropyrimidin-l(2 / 7)-yl)-l- methyl- l / / -indazol-7-yl)oxy)acetyl)piperazin- 1 -yl)hexyl)carbamoyl)phenyl)amino)-A^V- dimethyl-7Z / -pyrrolo[2,3-<7]pyrimidine-6-carboxamide A553;7-cyclopentyl-2-((4-((2-(4-(2-((3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)-l-methyl-177-indazol-6-yl)oxy)acetyl)piperazin-l -yl)ethyl)carbamoyl)phenyl)amino)-ArrA’- dimethyl-7 / 7-pyrrolo[2,3-< / ]pyrimidine-6-carboxaniide A554;7-cyclopentyl-2-((4-((4-(4-(2-((3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)-l- m ethyl- 1 AT-indazol-6-yl)oxy)acetyl)piperazin- 1 -yl)butyl)carbamoyl)phenyl)amino)-A,A- dimethyl-7H-pyrrolo[2,3-^jpyrimidine-6-carboxamide A555;7-cyclopentyl-2-((4-((6-(4-(2-((3-(2,4-dioxotetrahydropyrimidin-l(2 / / )-yl)-l- methyl- l / / -indazol-6-yl)oxy)acetyl)piperazin- 1 -yl)hexyl)carbamoyl)phenyl)amino)-A^V;- dimethyl-777-pyrrolo[2,3-<7]pyrimidine-6-carboxamide A556;7-cyclopentyl-2-((5-(4-(2-(3-(2,4-dioxotetrahydropyrimidin-l(22 / )-yl)-l -methyl- l / 7-indazol-6-yl)ethyl)-4-fluoro-[l ,4'-bipiperidin]-r-yl)pyridin-2-yl)amino)-A',A?-dimethyl-7H- pyrrolo[2,3-<7]pyrimidine-6-carboxamide A557;7-cyclopentyl-2-((5-(4-(2-(3-(2,4-dioxotetrahydropyrimidin- 1 (2H)-yV)- 1 -methyl- lZ / -indazol-7-yl)ethyl)-4-fluoro-[l,4'-bipiperidin]-r-yl)pyridin-2-yl)amino)-A,A-dimethyl-77A pyrrolo[2,3-^pynmidine-6-carboxamide A558;7-cyclopentyl-2-((5-(4-(2-(l-(3-(2,4-dioxotetrahydropyrimidin-l(2 / 7)-yl)-l- methyl-l / / -indazol-6-yl)piperidin-4-yl)etliyl)piperazin-l-yl)pyridin-2-yl)ainino)-Ar,AT-diniethyl- 777-pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A559;7-cyclopentyl-2-((4-((6-((2-(2,6-dioxopiperidin-3-yl)-l,3-dioxoisoindolin-4-yl)- amino)hexyl)carbamoyl)phenyl)amino)-AAV-dimethyl-7 / 7-pyrrolo[2,3-tZ]pyrimidine-6- carboxamide A601;7-cyclopentyl-2-((4-((6-((2-(2,6-dioxopiperidin-3-yl)-l,3-dioxoisoindolin-4-yl)- amino)hexyl)(methyl)carbamoyl)phenyl)amino)-A7,Af-dimethyl-7 / f-pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A602;7-cyclopentyl-2-((5-(4-((2-(2,6-dioxopiperidin-3-yl)-l,3-dioxoisoindolin-4-yl)- glycyl)piperazin-l-yl)pyridin-2-yl)amino)-jV,A / -dimethyl-7 / 7-pyrrolo[2,3~<7]pyrimidine-6- carboxamide A603;7-cyclopentyl-2-((5-(4-((2-(2,6-dioxopiperidin-3-yl)-l-oxoisoindolin-4-yl)- glycyl)piperazin-l-yl)pyri din-2 -yl)amino)-Ar,A-dimethyl-7 / / -pyrrolo[2,3-t / ]pyrimidine-6- carboxamide A611;7-cyclopentyl-2-((4-((2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxoisoindolin- 4-yl)piperi din- l-yl)ethyl)carbamoyl)phenyl)amino)-A’,ALdimethyl-7 / 7-pyrrolo[2, 3 -^pyrimidine-6-carboxamide A612;7-cyclopentyl-2-((4-((4-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxoisoindolin-4-yl)piperidin-l-yl)butyl)carbamoyl)phenyl)amino)-A’,7V-dimethyl-7 / 7-pyrrolo[2,3-< / ]pyrimidine- 6-carboxamide A613;7-cyclopentyl-2-((4-((6-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxoisoindolin-4-yl)piperidin-l-yl)hexyl)carbamoyl)phenyl)amino)-77,A / -dimethyl-7Z / -pyrrolo[2,3-«7]pyrimidine- 6-carboxamide A614;7-cyclopentyl-2-((5-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxo- isoindolin-4-yl)piperidin-l-yl)acetyl)piperazin-l-yl)pyridin-2-yl)amino)-A,Ar-dimethyl-7ZA pyrrol o[2, 3 -<7]pyrimidine-6-carboxamide A615;7-cyclopentyl-2-((5-(4-(3-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxo- isoindolin-4-yl)piperidin-l-yl)propanoyl)piperazin-l-yl)pyridin-2-yl)amino)-A’,A7-dimethyl-7Ar- pyrrolo[2,3-<7]pyrimidine-6-carboxamide A616;7-cyclopentyl-2-((5-(4-(4-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxo- isoindolin-4-yl)piperidin-l-yl)butanoyl)piperazin-l-yl)pyridin-2-yl)amino)-Az,Ar-dimethyl-777- pyrrolo[2,3-<7]pyrimidiiie-6-carboxamide A617;7-cyclopentyl-2-((4-((2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l -oxoisoindolin-5-yl)piperidin-l-yl)ethyl)carbamoyl)phenyl)amino)-A\A / -dimethyl-72 / -pyrrolo[2,3-< / ]pyrimidine-6-carboxamide A618;7-cyclopentyl-2-((4-((4-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxoisoindolin-5-yl)piperidin-l-yl)butyl)carbamoyl)phenyl)amino)-A,A-dimethyl-7 / / -pyrrolo[2,3-6(|pyrimidine-6-carboxamide A619;7-cyclopentyl-2-((4-((6-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxoisoindolin-5-yl)piperidin-l-yl)hexyl)carbamoyl)phenyl)amino)-Ar,A7-dimethyl-7 / f-pyrrolo[2,3-60pyrimidine-6-carboxamide A620,7-cyclopentyl-2-((5-(4-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxo- isoindolin-5-yl)piperidin-l-yl)acetyl)piperazin-l-yl)pyridin-2-yl)amino)-A,Ar-dimethyl-7Ar- pyrrol o[2, 3 -<7]pyrimidine-6-carboxamide A621;7-cy cl op enty 1 -2 -(( 5 -(4-(3 -(4-(2-(2, 6-dioxopiperidin-3 -yl)-6-fluoro- 1 -oxo- isoindolin-5-yl)piperidin-l-yl)propanoyl)piperazin-l-yl)pyridin-2-yl)amii]o)-A’,A7-dimethyl-7Ar- pyrrolo[2,3-rZ]pyrimidine-6-carboxamide A622;7-cyclopentyl-2-((5-(4-(4-(4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-l-oxo- isoindolin-5-yl)piperidin-l-yl)butanoyl)piperazin-l-yl)pyridin-2-yl)amino)-ArjV-dimethyl-7Jf- pyrrolo[2,3-tf]pyrimidine-6-carboxamide A623;7-cyclopentyl-2-((4-((4-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-427- thieno[3,4-c]pyiTol-l-yl)methoxy)benzyl)carbamoyl)phenyl)amino)-? / ,JV-dimethyl-777- pyrrolo[2,3-<7]pyrimidine-6-carboxamide A651;7-cyclopentyl-2-((4-((2-((4-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4 / 7- thieno[3,4-c]pyrrol-l-yl)methoxy)benzyl)amino)ethyl)carbamoyl)phenyl)amino)- / V,7V-dimethyl- 7 / 7-pyrrolo[2,3-t / ]pyrimidine-6-carboxamide A652;7-cyclopentyl-2-((4-((4-((4-((5-(2,6-dioxopiperidm-3-yl)-4-oxo-5,6-dihydro-4Z7- thieno[3,4-c]pyrrol-l-yl)methoxy)benzyl)aniiiio)butyl)carbamoyl)phenyl)amino)-7V,A7-dimethyl- 7 / 7-pyrrolo[2,3-<f|pyrimidine-6-carboxamide A653;7-cyclopentyl-2-((4-((4-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4 / f- thieno[3,4-c]pyirol-l-yl)methoxy)benzyl)carbamoyl)phenyl)amino)-Az,ALdimethyl-7H-pyrrolo- [2,3-< / ]pyrimidine-6-carboxamide A654;3-(3-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)-2-oxoethoxy)phenyl)piperidine-2, 6-dione B101;3-(3-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)-3-oxopropoxy)phenyl)piperidine-2, 6-dione B102;A-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t / ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)-2-(3-(2,6-dioxopiperidin-3-yl)-2- methylphenoxy)acetamide B103; jV-(2-(4-(6-((6-acetyi-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-tZ|- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)-2-(3-(2,6-dioxopiperidin-3-yl)-2- (trifluoromethyl)phenoxy)acetamide B104;7V-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)-2-(3-(2,6-dioxopiperidin-3-yl)-4- methylphenoxy)acetamide Bl 05;A7-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-tZ]-pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)-2-(3-(2,6-dioxopiperidin-3-yl)-4- (trifluoromethyl)phenoxy)acetamide Bl 06;Ar-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)propyl)-2-(3-(2,6-dioxopiperidin-3-yl)-2- methylphenoxy)acetamide B107;77-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yi)piperazin-l-yl)propyl)-2-(3-(2,6-dioxopiperidin-3-yl)-2- (tri fluorom ethy 1 )ph en oxy )acetam ide B 108 ;Az-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)propyl)-2-(3-(2,6-dioxopiperidin-3-yl)-4- methylphenoxy)acetamide B109;A'r-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-6f]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)propyl)-2-(3-(2,6-dioxopiperidin-3-yl)-4- (trifluoromethyl)phenoxy)acetamide B 110 ;3-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-6 / ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)phenyl)piperidine-2, 6-dione Bill;3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)phenyl)piperidine-2, 6-dione Bl 12;3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimi din-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)ethoxy)phenyl)piperidine-2, 6-dione Bl 13;3-(3-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)phenyl)piperidine-2, 6-dione B114;3-(3-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t7|- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)phenyl)piperidine-2, 6-dione B115;3-(3-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yi)piperazin-l-yl)ethoxy)phenyl)piperidine-2, 6-dione B116;3-(4-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)propoxy)phenyl)piperidine-2, 6-dione Bl 17;3-(3-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)propoxy)phenyl)piperidine-2, 6-dione B118;3-(4-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-6!0-pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)phenyl)piperidine-2, 6-dione B119;3-(4-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- < / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)piperi din- l-yl)phenyl)piperi dine-2,6-dione B120;3-(4-((4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-] -yl)piperidin-l-yl)methyl)phenyl)piperidine-2,6-dione B121;3-(3-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)phenyl)piperidine-2, 6-dione B122;3-(3-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- < / |pyrimidin-2-yl)aniino)pyridin-3-yl)piperazin-l-yl)methyl)piperi din- l-yl)phenyl)piperi dine-2,6-dione B123;3-(3-((4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyriniidin-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)piperi din- l-yl)methyl)phenyl)piperidine-2,6-dione B124;3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperazin-l-yl)phenyl)piperidine-2,6- dione B125;3-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t(|pyrimidin-2-yl)amino)pyridin-3 -yl)piperazin- 1 -yl)ethyl)piperazin- 1 -yl)phenyl)piperidine-2, 6- dione B126;3-(4-(2-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)ethyl)phenyl)piperidine-2,6- dione B127;3-(3-(2-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)ethyl)phenyl)piperidine-2,6- dione B128;3-(4-((l-(2-((4-((6-(difluoromethyl)-8-((l / ^2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-tZ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)ethyl)piperidin-4-y l)oxy )pheny l)pi peri dine-2, 6-dione Bl 29;3-(3-((l-(2-((4-((6-(difluoromethyl)-8-((17?,22?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)ethyl)piperi din-4- yl)oxy)phenyl)piperidine-2, 6-dione B130;3-(4-((l-(3-((4-((6-(difluoromethyl)-8-((l / ?,2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-tf]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propyl)piperidin-4- yl)oxy)phenyl)piperidine-2, 6-dione B131;3-(4-(4-(2-((4-((6-(difluoromethyl)-8-((17?,2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin- 1 -yl)sulfonyl)ethyl)piperazin- 1 - yl)phenyl)piperi dine-2, 6-dione B132;3-(4-(4-(2-((4-((6-(difluoromethyl)-8-((l / ^,2JR)-2-hydroxy-2-methylcyclopentyi)- 7-oxo-7,8-dihydropyrido[2,3-< / ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)ethyl)piperidin-l- yl)phenyl)piperidine-2, 6-dione B133;3-(4-(4-(3-((4-((6-(difluoromethyl)-8-((17?,2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-t / ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propyl)piperazin- l-yl)phenyl)piperi dine-2, 6-dione B134;3-(3-(4-(2-((4-((6-(difluoromethyl)-8-((17?,2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-J]pyrimidin-2-yl)aniino)piperidin- 1 -yl)sulfonyl)ethyl)piperazin- 1 - yl)phenyl)piperi dine-2, 6-dione B135;3-(3-(4-(3-((4-((6-(difluoromethyl)-8-((l / x',2 / ?)-2-hydroxy-2-methylcyclopentyi)- 7-oxo-7,8-dihydropyrido[2,3-tZ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propyl)piperazin- 1 -yl)phenyl)piperi dine-2, 6-dione B136;3-(4-(3-((4-((6-(difluoromethyl)-8-((12?,22?)-2-hydroxy-2-methylcyclopentyl)-7- oxo-7, 8-dihydropyrido[2,3-J]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propoxy)phenyl)- piperidine-2, 6-dione B137;3 -(3 -(3 -((4-((6-(difluoromethyl)-8-(( lA,2J?)-2-hydroxy-2-methylcyclopentyl)-7- oxo-7, 8-dihydropyrido[2,3-J]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propoxy)phenyl)- piperidine-2, 6-dione B138;3-(4-(4-(4-((4-((6-(diflUOrOmethyl)-8-((lJR,2JR)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-J]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)benzyl)piperazin- l-yl)phenyl)piperi dine-2, 6-dione B139;3-(4-(4-(3-((4-((6-(difluoromethyl)-8-((17?,2J?)-2-hydroxy-2-methylcyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-^pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)benzyl)piperazin-1 -yl)phenyl)piperi di ne-2, 6-dione B140;3-(3-(4-(3-((4-((6-(difluoromethyl)-8-((17?,2JR)-2-hydroxy-2-methylcyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-rf]pyrimidin-2-yl)amino)piperidin-l -yl)sulfonyl)benzyl)piperazin- l-yl)phenyl)piperidine-2, 6-dione B141;3-(3-(4-(4-((4-((6-(difluoromethyl)-8-((l / <27?)-2-hydroxy-2-methylcyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)sulfbnyl)benzyl)piperazin- l-yl)phenyl)piperidine-2, 6-dione B142, 3-(4-((4-(4-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenyl)piperazin- 1 -yl)methyl)phenyl)piperidine-2, 6-dione B143;3-(4-(4-((4-(4-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methyl- cyclopentyl)-7-oxo-7,8-dihydropyrido[2,3<fjpyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)- phenyl)piperazin-l-yl)methyl)piperidin-l-yl)phenyl)piperidine-2, 6-dione B144;3-(4-((4-((4-((6-(difluoromethyl)-8-((17?,2J?)-2-hydroxy-2-methylcyclopentyl)-7- oxo-7, 8-dihydropyrido[2, 3-tf|pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)piperazin-l-yl)- methyl)phenyl)piperidine-2, 6-dione B145;3-(3-((4-((4-((6-(difluoromethyl)-8-((l / ?,2 / ?)-2-hydroxy-2-methylcyclopentyl)-7- oxo-7, 8-dihydropyrido[2, 3-t / ]pyrimidin-2 -yl)amino)piperidin-l-yl)sulfonyl)piperazin-l-yl)- methyl)phenyl)piperidine-2, 6-dione B146;3-(4-(4-((4-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-t(|pyrimidin-2-yl)amino)piperidin-l -yl)sulfonyl)piperazin-l-yl)- methyl)piperidin-l-yl)phenyl)piperidine-2, 6-dione B147;3-(4-(4-(3-((4-((6-(diflUoromethyl)-8-((l / ^2JR)-2-hydroxy-2-methylcyclopentyl)" 7-oxo-7, 8-dihy dropyrido[2, 3 - J]pyrimidin-2-yl)ami no)piperi din- 1 -y l)sulfonyl)propy I )pi perazin- l-yl)phenyl)piperidine-2, 6-dione B148;3-(3-((l-(3-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-< / ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfdnyl)propyl)piperidin-4- yl)oxy)phenyl)piperidine-2, 6-dione B149;3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l -yl)phenyl)piperidine-2,6- dione B150;3-(4-(2-(4-(4-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclo- pentyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenyl)- piperazin- 1 -y 1 )ethy l)ph enyl)piperidine-2 , 6-di one B151 ;3-(4-(2-(4-(4-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclo- pentyl)-7-oxo-7,8-dihydropyrido[2,3-c(jpyrimidin-2-yl)amino)piperidin-l-yi)sulfonyl)phenyl)- piperazin- l-yl)ethoxy)phenyl)piperidine-2, 6-dione B152;3-(4-(2-(4-(3-((4-((6-(difluoromethyl)-8-((17?,22?)-2-hydroxy-2-methylcyclo- pentyl)-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenyi)- piperazin- 1 -yl)ethyl)phenyl)piperidine-2, 6-dione B153;3-(3-(2-(4-((4-((6-(difluoromethyl)-8-((l / ^,27?)-2-hydroxy-2-methylcyclopentyl)-7-oxO"7,8-dihydropyrido[2,3-J]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)piperazin-l-yl)- ethoxy)phenyl)piperidine-2, 6-dione B154;3-(4-(3-(4-((4-((6-(difluoromethyl)-8-((17?,2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-< / Jpyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)piperazin-l-yl)- propoxy )phenyl)piperidine-2, 6-dione Bl 55;3-(3-(3-(4-((4-((6-(difluoromethyl)-8-((lJR,2 / ^)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3W]pyrimidin-2-yl)amino)piperidin-l-yl)sulfdnyl)piperazin-l-yl)- propoxy )phenyl)piperidine-2, 6-dione B156;3-(4-(4-(4-((4-((6-(difluoromethyl)-8-((l / ^2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-tZ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenethyl)- piperazin-l-yl)phenyl)piperidine-2, 6-di one B157;3-(4-(4-(2-(4-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclo- pentyl)-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)aniino)piperidin-l-yl)sulfonyl)phenoxy)- ethyl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B158;3-(4-(4-(2-(3-((4-((6-(difluoromethyl)-8-((17?,2 / 7)-2-hydroxy-2-methylcyclo- pentyl)-7-oxo-7,8-dihydropyrido[2,3-t / jpyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenoxy)- ethyl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B159;3-(3-((l-(3-((4-((6-(difluoromethyl)-8-((l / ^2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-^]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenyl)piperidin-4-yl)oxy)phenyl)piperidine-2, 6-dione B160;3-(4-((l-(3-((4-((6-(difluoromethyl)-8-((17?,22?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenyl)piperidin- 4-yl)oxy)phenyl)piperidine-2, 6-dione B161;3-(4-((l-(4-((4-((6-(difluoromethyl)-8-((l / ?,2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-tf]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenyl)piperidin- 4-yl)oxy)phenyl)piperidme-2, 6-dione B162;3-(4-(4-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZjpyrimidin-2-yl)amino)pyridin-3 -yl)piperazin- 1 -yl)propyl)piperazin- 1 -yl)phenyl)piperidine- 2, 6-dione B163;3-(4-(4-((4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)aniino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)methyl)piperidin-l-yl)- phenyl)piperidine-2, 6-dione B164;3-(4-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)-[l,4'-bipiperidin]-r-yl)phenyl)- piperidine-2, 6-dione B165;3-(4-(4-(l-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-< / jpyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-4-yl)piperazin-l-yl)- phenyl)piperidine-2, 6-dione Bl 66;3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyi-5-methyl-7-oxo-7,8-dihydropyrido[2,3~ d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1 -yl)ethyl)-[1 ,4'-bipiperidin]-r-yl)phenyl)- piperidine-2, 6-dione B167;3-(4-(4-(3-((4-((8-cyclopentyl-7-oxo-7,8-dihydropyrido[2,3-J]pyrimidin-2-yl)- amino)piperi din- l-yl)sulfonyl)propyl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B168;3-(4-(4-(3-((4-((8-cyclopentyl-6-(difluoromethyl)-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)aniino)piperidin-l-yl)sulfonyl)propyl)piperazin-l-yl)phenyl)piperidine-2,6- dione B169;3-(4-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-(f|- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2,6- dione B170;3-(4-(4-((3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyi-7-oxo-7,8-dihydropyrido-[2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)methyl)piperidin-l-yl)- phenyl)piperidine-2, 6-dione B171;3-(4-((5)-2-((4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-tZ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin- 1 -y l)piperi din- 1 -yljmethyl)- morpholino)phenyl)piperidine-2, 6-dione B172;3-(4-((7?)-2-((4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-< / Jpyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)methyl)- morpholino)phenyl)piperidine-2, 6-dione B173;3-(4-((4-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-< / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)cyclohexyl)piperidin-l -yl)methyl)- phenyl)piperidine-2, 6-dione B174;3-(4-(2-(4-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)cyclohexyl)piperidin-l-yl)ethyl)- phenyl)piperidine-2, 6-di one Bl 75;3-(4-(3-((4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-t(|pyrimidin-2-yl)aniino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)methyl)azetidin-l-yl)- phenyl)piperidine-2, 6-dione Bl 76;3-(4-(4-((5)-2-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3W]pyriniidin-2-yl)amino)pyridin-3-yl)piperazin-l -yl)methyl)morpholino)piperi din-1- yl)phenyl)piperidine-2, 6-dione B177;3-(4-(4-(( / ?)-2-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-t(]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)morpholino)piperidin-l- yl)phenyl)piperidine-2, 6-dione B178;3-(4-(4-(4-((4-(6-((6-acetyl-8-cyclOpentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-c / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)cyclohexyl)piperazin-l-yl)- phenyl)piperi dine-2, 6-dione Bl 79;3-(4-(4-(2-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)ethyl)piperazin-l-yl)- phenyl)piperidine-2, 6-dione B180;3-(4-(2-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)cyclohexyl)ethyi)phenyi)piperidine-2,6-dione B181;3-(4-(4-(3-(4-(6-((6-Acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- d / pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)cyclohexyl)piperazin-l-yl)phenyl)- piperidine-2, 6-dione B182;3-(4-(4-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)propyl)piperidin-l-yl)phenyl)piperidine-2,6- dione B183;3-(4-(3-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZjpyrimidin-2-yl)amino)pyridin-3 -yl)piperazin- 1 -yl)piperidin- 1 -yl)propoxy)phenyl)piperidine-2, 6-dione B184;3-(4-(r-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-^pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)-[4,4'-bipiperidin]-l-yl)phenyl)- piperidine-2, 6-dione Bi 85:3-(4-(4-((3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-< / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)azetidin-l-yl)methyl)piperidin-l-yl)- phenyl)piperidine-2, 6-dione B186;3-(4-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2yl)amino)pyridin-3-yl)piperazin-l-yl)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2,6- dione B187;3-(4-(4-(r-(6-((6-acetyl-8-CyClOpentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t7jpyrimidin-2-yl)amino)pyridin-3-yl)-[l ,4'-bipiperidin]-4-yl)piperazin-l-yl)phenyl)piperidine-2,6-dione B188;3-(4-(4-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- cZ]pyrimidin-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)cy cl ohexyl)piperazin-l-yl)phenyl)- piperidine-2, 6-dione B189;3-(4-(4-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- J]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)cyclohexyl)piperidin-l-yl)phenyl)- piperidine-2, 6-dione B190;3-(3-(2-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2 -yl)amino)pyridin-3-yl)piperazin-l-yl)piperi din-1 -yl)ethoxy)phenyl)piperidine-2, 6-dione B191;3-(3-(3-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tflpyrimidin-2 -yl)amino)pyri din-3 -yl)piperazin-l-yl)piperidin-l-yl)propoxy)phenyl)piperi dine-2, 6-dione B192;3-(4-(4-(l-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- J]pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-4-yl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B193;3-(4-(4-(4-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperazin-l-yl)piperidin-l-yl)phenyl)piperidine-2,6-dione B194;3-(4-(r-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / |- yrimidin-2-yl)amino)pyridin-3-yl)methyl)-[4,4'-bipiperidin]-l-yl)phenyl)piperidine-2, 6-dione B195;3-(4-(4-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J]- pyrimidin-2-yl)amino)pyridin-3-yl)methyl)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2, 6-dione B196;3-(4-(4-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J|- pyrimidin-2-yl)amino)pyridin-3-yl)oxy)-[l,4'-bipiperidin]-T-yl)phenyl)piperidine-2, 6-dione B197;3-(4-(4-(2-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-(7]- pyrimidin-2-yl)amino)pyridin-3-yl)ethyl)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2, 6-dione B198;3-(4-(4-(((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]- pyrimidin-2-yl)amino)pyridin-3-yl)oxy)rnethyl)-[l,4'-bipiperidin]-l'-yl)phenyl)piperidine-2,6- dione B199;3-(4-(4-(4-(2-(6-((6-acetyl-8-cyclopentyi-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)ethyl)piperazin-l-yl)piperidin-l-yl)phenyl)piperidine-2,6- dione B200;3-(4-(4-(l-(2-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)ethyl)piperidin-4-yl)piperazin-l-yl)phenyl)piperidine-2,6- di one B201;3-(4-(r-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3t / ]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)-[4,4'-bipiperidin]-l-yl)phenyl)piperidine-2,6- dione B202;3-(4-(4-(l-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)piperidin-4-yl)piperazin-l-yl)phenyl)- piperidine-2, 6-dione B203;3-(4-(4-(4-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-< / ]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)piperazin-l-yl)piperidin-l-yl)phenyl)- piperidine-2, 6-dione B204;3-(4-(4-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)etliyl)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2,6- dione B205;3-(4-(r-(3-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)propyl)-[4,4'-bipiperidin]-l-yl)phenyl)piperidine-2,6-dione B206;3-(4-(4-(l-(3-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)propyl)piperidin-4-yl)piperazin-l-yl)phenyl)piperidine-2,6- di one B207;3-(4-(4-(4-(3-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZ]pyrimidin-2-yl)amino)pyridin-3-yl)propyl)piperazin-l-yl)piperidin-l -yl)phenyl)piperidine-2,6- dione B208;3-(4-(4-(3-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / |- pyrimidin-2-yl)amino)pyridin-3-yl)propyl)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2, 6-dione B209;3-(3-(4-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperazin-l-yl)phenyl)piperidine- 2,6-dione B210;3-(4-(4-(((5)-4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-t / ]pyrimidin-2-yl)amino)pyridin-3-yl)morpholin-2-yl)methyl)piperazin-l-yl)phenyl)- piperidine-2, 6-dione B211;3-(4-(4-((( / ?)-4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)morpholin-2-yl)methyl)piperazin-l-yl)phenyl)-piperidine-2, 6-dione B212;3-(3-(4-(((<S)-4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)aniino)pyridin-3-yl)morpholin-2-yl)methyl)piperazin-l -yl)phenyl)- piperidine-2, 6-dione B213;3-(4-(2-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)ethyl)phenyl)piperidine-2,6- dione B214;3-(4-(2-(r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZjpyrimidin-2-yl)amino)pyridin-3-yl)-[l,4'-bipiperidin]-4-yl)ethyl)phenyl)piperidine-2, 6-dione B215;3-(4-((5)-2-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)aniino)pyridin-3-yl)piperazin-l-yl)methyl)morpholino)phenyl)piperidine- 2,6-dione B216;3-(4-((7?)-2-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3 -< / ]pyrimidin-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)methyl)morpholino)phenyl)piperi dine- 2,6-dione B217;3-(4-(3-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]- pyrimidin-2-yl)amino)pyridin-3-yl)oxy)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2, 6-dione B218;3-(4-(4-(l-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- d]pyrimidin-2-yl)amino)pyridin-3-yl)methyl)piperidin-3-yl)piperazin-l-yl)phenyl)piperidine- 2,6-dione B219;3-(3-(4-(l-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- cZ]pyrimi din-2-yl)amino)pyri din-3 -yl)methyl)piperi din-3 -yl)piperazin-l-yl)phenyl)piperi dine- 2,6-dione B220;3-(4-(4-(l-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-tZjpyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)piperidin-3-yl)piperazin-l-yl)phenyl)- piperidine-2, 6-dione B221;3-(3-(4-(l-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)piperidin-3-yl)piperazin-l-yl)phenyl)- piperidine-2, 6-dione B222;3-(3-(4-(l-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3 -cZ]pyrimi din-2 -yl)amino)pyri din-3 -yl)piperidin-4-yl)methyl)piperidin-4-yl)piperazin-l-yl)- phenyl)piperidine-2, 6-dione B223;3-(4-(4-(l-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3 -<7]pyrimidin-2-yl)amino)pyri din-3 -yl)piperidin-4-yl)methyl)piperidin-4-yl)piperazin-l-yl)- phenyl)piperidine-2, 6-dione B224;3-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B225,3-(4-(4-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- ef|pyrimidin-2-yl)amino)pyridin-3-yl)azetidin-3-yl)methyl)piperazin-l-yl)plienyl)piperidine-2,6- di one B226;3-(4-(4-(2-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- iZ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)ethyl)piperazin-l-yl)phenyl)piperidine-2,6- dione B227;3-(4-(3-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)azetidin-l-yl)phenyl)piperidine-2,6- dione B228;3-(4-(2-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- c / ]pyriniidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)-2,7-diazaspiro[3.5]nonan-7- yl)phenyl)piperidine-2, 6-dione B229;3-(4-(4-(3-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / jpyrimidin-2-yl)amino)pyridin-3-yl)oxy)propyl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B230;3-(4-(l-(3-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxO"7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)aniino)pyridin-3-yl)oxy)propyl)piperidin-4-yl)phenyl)piperidine-2, 6-dione B231;3-(3-(4-(3-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- < / ]pyrimidin-2 -yl)amino)pyri din-3 -yl)oxy)propyl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B232;3-(3-(l-(3-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3t / ]pyriniidin-2-yl)amino)pyridin-3-yl)oxy)propyl)piperidin-4-yl)phenyl)piperidine-2, 6-dione B233;3-(4-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyri din-3 -yl)piperi din- l-yl)propoxy)phenyl)piperidine-2, 6-dione B234;3-(4-(4-(3-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)propyl)piperidin-l-yl)phenyl)piperidine-2,6-dione B235;3-(3-(4-(3-((6-((6-acetyl-8-cyclopentyl-5-metliyl-7-oxo-7,8-dihydropyrido[2,3- tZjpyrimidin-2-yl)amino)pyridin-3 -yl)oxy)propyl)piperi din- l-yl)phenyl)piperidine-2, 6-dione B236;3-(4-(3-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)propoxy)phenyl)piperidine-2, 6-dione B237;3-(4-(4-(6-((6-acetyl-8-cycIopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-£Zj- pyrimidin-2-yl)amino)pyridin-3-yl)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2, 6-dione B238;3-(4-(r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / |- pyrimidin-2-yl)amino)pyridin-3-yl)-[4,4'-bipiperidin]-l-yl)phenyl)piperidine-2, 6-dione B239;3-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B240;3-(4-(r-(6-((6-aCetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-dF]- pyrimidin-2-yl)amino)pyridin-3-yl)-[l,4'-bipiperidin]-4-yl)phenyl)piperidine-2, 6-dione B241;3-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t(]- pyrimidin-2-yl)amino)pyridin-3-yl)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2, 6-dione B242;3-(3-(r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-tZ]- pyrimidin-2-yl)amino)pyridin-3-yl)-[4,4'-bipiperidin]-l-yl)phenyl)piperidine-2, 6-dione B243;3-(3-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-60- pyrimidin-2-yl)amino)pyridin-3 -yl)piperidin-4-yl)piperazin- 1 -yl)phenyl)piperidine-2, 6-dione B244;3-(3-(r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / |" pyrimidin-2-yl)amino)pyridin-3-yl)-[l,4'-bipiperidin]-4-yl)phenyl)piperidine-2, 6-dione B245;3-(4-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-niethyl-7-oxo-7,8-dihydropyrido[2,3-t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)methyl)piperidin-l-yl)phenyl)piperidine-2,6- dione B246;3-(4-(4-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- < / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperazin-l-yl)phenyl)piperidine- 2,6-dione B247;3-(4-(l-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperidin-4-yl)phenyl)piperidine-2,6- di one B248;3-(3-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)methyl)piperidin-l-yl)phenyl)piperidine-2,6- dione B249;3-(3-(l-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperidin-4-yl)phenyl)piperidine-2,6- dione B250;3-(3-(4-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)methyl)piperidin-l-yl)phenyl)piperidine-2,6- di one B251;3-(4-(l'-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]- pyrimidin-2-yl)amino)pyridin-3-yI)methyl)-[l ,4'-bipiperidin]-4-yl)phenyl)piperidine-2, 6-dione B252;3-(4-(l-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tf|pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-4-yl)phenyl)piperidine-2,6- dione B253;3-(4-(l-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- < / |pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)ethyl)piperidin-4-yl)phenyl)piperidine-2,6- dione B254;3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)ethyl)piperazin-l -yl)phenyl)piperidine-2,6- dione B255;3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)ethyl)piperidin-l-yl)phenyl)piperidine-2,6-dione B256;3-(3-(l-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-4-yl)phenyl)piperidine-2,6- di one B257;3-(3-(l-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)ethyl)piperidin-4-yl)phenyl)piperidine-2,6- di one B258;3-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)ethyl)piperazin-l-yl)phenyl)piperidine-2,6- dione B259;3-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyi-5-methyl-7-oxo-7,8-dihydropyrido[2,3- d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)ethyl)piperidin-l-yl)phenyl)piperidine-2,6- dione B260;3-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2 -yl)amino)pyri din-3 -yl)piperazin-l-yl)ethyl)piperi din- l-yl)phenyl)piperidine-2,6- di one B261;3-(4-(2-(r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]- pyrimidin-2-yl)amino)pyridin-3-yl)-[4,4'-bipiperidin]-l-yl)ethyl)phenyl)piperidine-2, 6-dione B262;3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)-[l,4'-bipiperidin]-r-yl)ethyl)phenyl)piperidine-2, 6-dione B263;3-(3-(4-(4-(2-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- cZ]pyrimidin-2-yl)amino)pyridin-3-yl)ethyl)piperazin-l-yl)piperidin-l-yi)phenyl)piperidine-2,6- dione B264;3-(3-(4-(2-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)ethyl)-[l,4'-bipiperidin]-r-yl)phenyl)piperidine-2, 6-dione B265;3-(3-(4-(((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)oxy)methyl)-[l,4'-bipiperidin]-l'-yl)phenyl)piperidine-2,6- dione B266;3-(3-(r-(2-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)ethyl)-[4,4'-bipiperidin]-l-yl)phenyl)piperidine-2, 6-dione B267;3-(3-(4-(l-(2-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7jpyrimidin-2-yl)amino)pyridin-3-yl)ethyl)piperidin-4-yl)piperazin-l -yl)phenyl)piperidine-2,6- dione B268;3-(3-(4-(l-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)piperidin-4-yl)piperazin-l-yi)phenyl)- piperidine-2, 6-dione B269;3-(3-(4-(4-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido-[2,3 -< / ]pyrimidin-2-yl)amino)pyri din-3 -yl)oxy)ethyl)piperazin-l-yl)piperi din- l-yl)phenyl)- piperidine-2, 6-dione B270;3-(4-(r-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-Jjpyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)-[l,4'-bipiperidin]-4-yl)phenyl)piperidine-2,6- dione B271;3-(4-(4-(2-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)ethyl)piperidin-l -yl)phenyl)piperidine-2,6- dione B272;(S)-3-(4-(4-(((S)-4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-<7]pyriniidin-2-yl)amino)pyridin-3-yl)morpholin-2-yl)niethyl)piperazin-l-yl)phenyl)- 3-methylpiperidine-2, 6-dione B273;3-(4-(l-(2-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- Jjpyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)ethyl)piperidin-4-yl)phenyl)piperidine-2,6- dione B274;3-(4-((r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J]- pyrimidin-2-yl)amino)pyridin-3-yi)-[l ,4'-bipiperidin]-4-yi)niethyl)phenyl)piperidine-2!6-dione B275;3-(4-(4-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J]- pyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B276;3-(4-(4-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]- pyrimidin-2-yl)amino)pyridin-3-yl)oxy)ethyi)piperidin-l-yl)phenyl)piperidine-2, 6-dione B277;3-(4-(2-(r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZ]pyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoro-[l,4'-bipiperidin]-4-yl)ethyl)phenyl)piperidine- 2,6-dione B278;3-(3-(3-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7jpyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)azetidin-l-yl)phenyl)piperidine-2,6- dione B279;3-(4-(2-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin- l-yl)piperidin- 1 -yl)- 1 , 1 -difluoroethyl)phenyl)- piperidine-2, 6-dione B280;3-(3-(2-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyri din-3 -yl)piperazin- 1 -y l)piperi din- 1 -yl)- 1 , 1 -difluoroethyl)phenyl)- piperidine-2, 6-dione B281;3-(4-(2-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)azetidin-l-yl)-l, l-difluoroethyl)phenyl)- piperidine-2, 6-dione B282;3-(3-(2-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tf|pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)azetidin-l-yl)-l,l-difluoroethyl)phenyl)- piperidine-2, 6-dione B283;3-(4-((3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- c / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)azetidin-l-yl)methyl)phenyl)piperidine-2,6- di one B284;3-(3-((3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / jpyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)azetidin-l-yl)methyl)phenyl)piperidine-2,6- dione B285;3-(3-(2-(l'-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoro-[l,4'-bipiperidin]-4-yl)ethyl)phenyl)piperidine- 2,6-dione B286;3-(4-((r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-tf|- pyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoro-[l,4'-bipiperidin]-4-yl)methyl)phenyl)piperidine- 2,6-dione B287;3-(3-((r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]-pyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoro-[l ,4'-bipiperidin]-4-yl)methyl)phenyl)piperidine- 2,6-dione B288;3-(4-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- < / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazeti din-3 -yl)ethyl)phenyl)- piperidine-2, 6-dione B289;3-(3-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazetidin-3-yl)ethyl)phenyl)- piperidine-2, 6-dione B290;3-(4-((l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyriniidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazetidin-3-yl)methyl)phenyl)- piperidine-2, 6-dione B291;3-(3-((l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7Jpyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazeti din-3 -yl)methyl)phenyl)- piperidine-2, 6-dione B292;3-(4-(l-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyriniidin-2-yl)amino)pyridin-3-yl)-4-fluoropiperidin-4-yl)methyl)azetidin-3-yl)phenyl)- piperidine-2, 6-dione B293;3-(3-(l-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZ]pyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoropiperidin-4-yl)methyl)azetidin-3-yl)phenyl)- piperidine-2, 6-dione B294;3-(4-(2-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tflpyrimidin-2-yl)amino)pyridin-3-yl)azetidin-3-yl)piperazin-l-yl)ethyl)phenyl)piperidine-2,6- dione B295;3-(3-(2-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyriniidin-2-yl)amino)pyridin-3-yl)azetidin-3-yl)piperazin-l-yl)ethyl)phenyl)piperidine-2,6- dione B296;3-(4-((4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)azetidin-3-yl)piperazin-l-yl)methyl)phenyl)piperidine-2,6- di one B297;3-(3-((4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)azetidin-3-yl)piperazin-l-yl)methyl)phenyl)piperidine-2,6-dione B298;3-(3-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- d]pyrimidin-2-yl)amino)pyridin-3-yl)azetidin-3-yl)piperidin-4-yl)ethyl)phenyl)piperidine-2,6- dione B299;3-(3-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)azetidin-3-yl)-4-fluoropiperidin-4-yl)ethyl)phenyl)- piperidine-2, 6-dione B300;3-(3-(8-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t(jpyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)-3-azabicyclo[3.2.1]octan-3-yl)- phenyl)piperidine-2, 6-dione B301;3-(3-(3-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)-8-azabicyclo[3.2.1]octan-8-yl)- phenyl)piperidine-2, 6-dione B302;3-(3-(4-((3-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J]pyrimidin-2-yl)amino)pyridin-3-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-l-yl)- phenyl)piperidine-2, 6-dione B303;3-(3-(4-((8-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- Jjpyrimidin-2-yl)amino)pyridin-3-yl)-3,8-diazabicyclo[3.2.1]octan-3-yl)methyl)piperidin-l-yl)- phenyl)piperidine-2, 6-dione B304;3-(3-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- d]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)methyl)-4-fluoropiperidin-l-yl)phenyl)- piperidine-2, 6-dione B305;3-(4-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- cZ]pyrimidin-2-yl)amino)pyri din-3 -yl)piperidin-l-yl)methyl)-4-fluoropiperi din- l-yl)phenyl)- piperidine-2, 6-dione B306;(5)-3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-J]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)phenyl)-3-methyl- piperidine-2, 6-dione B307;(7?)-3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l -yl)ethyl)piperidin-l-yl)phenyl)-3-methyl- piperidine-2, 6-dione B308;-3-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2, 3 -t / ]pyrimi din-2 -yl)amino)pyri din-3 -yl)piperidin-4-yl)piperazin-l-yl)phenyl)-3 -methyl- piperidine-2, 6-dione B309;(7?)-3-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)phenyl)-3-methyl- piperidine-2, 6-dione B310;3-(4-(l-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoropiperidin-4-yl)methyl)piperidin-4-yl)phenyl)- piperidine-2, 6-dione B311;3-(3-(l-((l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoropiperidin-4-yl)methyl)piperidin-4-yl)phenyl)- piperidine-2, 6-dione B312;3-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / |- pyrimidin-2-yl)amino)pyridin-3 -yl)piperidin-4-yl)piperazin- 1 -yl)-2-fluorophenyl)piperi dine-2,6- dione B313;3-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]- pyrimidin-2-yl)arnino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-3-fluorophenyl)piperidine-2,6- dione B314;3-(4-(4-( l-(6-((6-acetyl-8-cyclOpentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-(7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-chlorophenyl)piperidine-2,6- dione B315;3-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-J]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-3-chlorophenyl)piperidine-2,6- di one B316;3-(4-(3-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimi din-2-yl)amino)pyri din-3 -yi)pi perazin- 1 -yl)azeti din- 1 -yl)phenyl)piperidine-2, 6-di one B317;3-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-5-fluorophenyl)- piperidine-2, 6-di one B318;3-(5-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l -yl)-2-fluorophenyl)- piperidine-2, 6-dione B319;3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t7]pyrimidin-2-yl)amino)pyridin-3 -yl)piperazin- 1 -y 1 )ethy l)pi p eri di n- 1 -yl)-3 -fluorophenyl)- piperidine-2, 6-dione B320;3-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-] -yl)ethyl)piperidin-l-yl)-2-fluorophenyl)- piperidine-2, 6-dione B321;3-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyriniidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l -yl)-2-fluorophenyl)- piperidine-2, 6-dione B322;3-(3-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)-4-fluoropiperidin-l-yl)phenyl)- piperidine-2, 6-dione B323;3-(4-(4-(4-(2-((6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3 -< / |pyrimidin-2-yl)amino)pyri din-3 -yl)oxy)ethyl)piperazin-l-yl)piperi din- l-yl)phenyl)- piperidine-2, 6-dione B324;3-(4-(2-((4-((6-(difluoromethyl)-8-((17x’,27?)-2-hydroxy-2-methylcyclopentyl)-7- oxo-7, 8-dihydropyrido[2,3-J]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)ethoxy)phenyl)- piperidine-2, 6-dione B351;3-(4-(4-(((4-((6-(difluoromethyl)-8-((l / ?,27?)-2-hydroxy-2-methylcyclopentyl)-7- oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)methyl)piperidin-l- yl)phenyl)piperidine-2, 6-dione B352;3-(3-(2-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)-7- oxo-7, 8-dihydropyrido[2,3-t / ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)ethoxy)phenyl)- piperidine-2, 6-dione B353;3-(4-(4-(((4-((6-(difluoromethyl)-8-((l / 7,27?)-2-hydroxy-2-methylcyciopentyl)-7- oxo-7,8-dihydropyrido[2,3-t / ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)methyl)-[l,4'- bipiperi din]- l'-yl)phenyl)piperidine-2, 6-dione B354;3-(4-(4-(l-(2-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methyl- cyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-tZ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)-ethyl)piperidin-4-yl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B355;3-(4-((4-(3-((4-((6-(difluoromethyl)-8-((lJ?,22?)-2-hydroxy-2-methylcyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)phenyl)piperazin- l-yl)methyl)phenyl)piperidine-2, 6-dione B356;3-(4-(4-((4-(3-((4-((6-(difluoromethyl)-8-((l / ?,2 / ?)-2-hydroxy-2-methyl- cyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)- phenyl)piperazin-l-yl)methyl)piperidin-l-yl)phenyl)piperidine-2, 6-dione B357;4-(3-(4-((4-(3-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methyl- cyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-r / ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)- phenyl)piperazin-l -yl)methyl)piperidin-l -yl)phenyl)piperidine-2, 6-dione B358;3-(4-(2-(4-((4-((6-(difluoromethyl)-8-((l / ^2JR)-2-hydroxy-2-methylcyclopentyi)-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)piperazin-l-yl)- ethyl)phenyl)piperidine-2, 6-dione B359;3-(4-(4-(4-((4-((6-(difluoromethyl)-8-((17?,2 / ?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-t / ]pyrimidin-2-yl)amino)piperidin- 1 -yl)sulfonyl)piperazin- 1 -yl)- piperi din- l-yl)phenyl)piperidine-2, 6-dione B360;3-(3-((l -(3-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-J]pyrimidin-2-yl)aniino)piperidin-l-yl)sulfonyl)propyl)piperidin-4- yl)oxy)phenyl)-3-methylpiperidine-2, 6-dione B361 ;3-(4-((l-(3-((4-((6-(difluoroniethyl)-8-((l / 7,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-tZ]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propyl)piperidin-4- yl)oxy)phenyl)-3-methylpiperidine-2, 6-dione B362;3-(3-(4-((3-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- cZ]pyrimi din-2-yl)amino)pyri din-3 -yl)azeti din- 1 -yl)methyl)-4-fluoropiperi din- 1 -yl)phenyl)- piperidine-2, 6-dione B363;3-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)azetidin-3-yl)piperazin-l-yl)phenyl)piperidine-2, 6-dione B364;3-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t7jpyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l -yl)ethyl)piperidin-l-yl)-4-fluorophenyl)- piperidine-2, 6-dione B365;3-(3-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZ]pyrimidin-2-yl)amino)pyri din-3 -yl)piperidin-l-yl)methyl)-4-fluoropiperi din- l-yl)phenyl)-3- methylpiperidine-2, 6-dione B366;(5)-3-(3-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)methyl)-4-fluoropiperidin-l-yl)phenyl)- 3 -methylpiperidine-2, 6-dione B367;(5)-3-(4-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazetidin-3-yl)ethyl)phenyl)-3- methylpiperidine-2, 6-dione B368;(7?)-3-(4-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-cZ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazetidin-3-yl)ethyl)phenyl)-3- methylpiperidine-2, 6-dione B369;3-(4-(7-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / |- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl)phenyl)- piperidine-2, 6-dione B370; -3-(4-((7?)-2-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-< / |pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)morpholino)phenyl)-3- methylpiperidine-2, 6-dione B371;(S)-3-(4-((7?)-2-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-<7]pyriniidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)morpholino)phenyl)-3- methylpiperidine-2, 6-dione B372;(7?)-3-(4-((7?)-2-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-tZ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)methyl)morpholino)phenyl)-3- methylpiperidine-2, 6-dione B373;(5)-3-(4-(( / ^)-2-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-l-yl)methyl)morpholino)phenyl)-3- methylpiperidine-2, 6-dione B374;(7?)-3-(4-(4-(((lS)-4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro- pyrido[2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)morpholin-2-yl)methyl)piperazin-l-yl)phenyl)- 3 -methylpiperidine-2, 6-dione B375; l-(4-((l-(3-((4-((6-(difluoro-methyl)-8-((lJR,27?)-2-hydroxy-2-methylcyclo-pentyl)-7-oxo-7,8-dihydropyrido[2,3-t7]pyrimidin-2-yl)amino)piperidin-l -yl)sulfonyl)propyl)- piperidin-4-yl)oxy)phenyl)dihydropyrimidine-2, 4(177, 377)-dione B401; l-(4-(4-(3-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-t7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propyl)piperazin- l-yl)phenyl)dihydropyrimidine-2, 4(177, 377)-dione B402; l-(2-chloro-4-(4-(3-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methyl- cyclopentyl)-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)- propyl)piperazin-l-yl)phenyl)dihydropyrimidine-2, 4(177, 377)-dione B403; l-(4-(4-(3-((4-((6-(difluoromethyl)-8-((17?,27?)-2-hydroxy-2-methylcyclopentyl)- 7-oxo-7,8-dihydropyrido[2,3-«7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propyl)piperazin- l-yl)-2-fluorophenyl)dihydropyrimidine-2, 4(177, 377)-dione B404; l-(4-(4-(3-((4-((6-(difluoromethyl)-8-((177,27?)-2-hydroxy-2-methylcyclopentyl)-7-oxO"7,8-dihydropyrido[2,3-t7]pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propyl)piperazin- l-yl)-2-methylphenyl)dihydropyrimidine-2, 4(177, 37 / )-dione B405; l-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t7|pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)phenyl)dihydro- pyrimidine-2, 4(177, 377)-dione B406; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-€f|- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)phenyl)dihydropyrimidine- 2,4(177,377)-dione B407; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-fluorophenyl)dihydro- pyrimidine-2, 4(177, 377)-dione B408; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyi-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7|- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-chlorophenyl)dihydro- pyrimidine-2, 4(177, 37 / )-dione B409; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-(7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-(trifluoromethyl)phenyi)- dihydropyrimidine-2, 4(177, 377)-dione B410; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yi)piperazin-l-yl)-2-methylphenyl)dihydro-pyrimidine-2, 4(177, 377)-di one B411 ; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2,3-dimethylphenyl)dihydro- pyrimidine-2, 4(177, 377)-dione B412; l-(5-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2 -yl)amino)pyri din-3 -yl)piperazin-l-yl)ethyl)piperi din- l-yl)-2,4-dimethylphenyl)- dihydropyrimidine-2,4( 177,377)-dione B413; l-(5-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t7|pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-2-chl oro-3 -methyl- phenyl)dihydropyrimidine-2,4(177,377)-dione B414; l-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyi-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-5-chloro-2-methyl- phenyl)dihydropyrimidine-2, 4(177, 377)-dione B415; l-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperazin-l-yl)phenyl)dihydro- pyrimidine-2, 4(177, 377)-dione B416; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-chloro-5-methylphenyl)- dihydropyrimidine-2, 4(177, 37 / )-dione B451; l-(4-(4-(l-(6-((6-aCetyl-8-cyClOpentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-fluoro-3-methylphenyl)- dihydropyrimidine-2,4(177,377)-dione B452; l-(4-(4-(l-6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-z7|- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-fluoro-5-methylphenyl)- dihydropyrimidine-2,4(177,377)-dione B453; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-2-chloro-6-methylphenyl)- dihydropyrimidine-2, 4(177, 37 / )-dione B454; l-(4-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-3-fluoro-2-methylphenyl)- dihydropyrimidine-2,4(177,377)-dione B455;l-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- tZ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)phenyl)dihydro- pyrimidine-2, 4(177, 377)-dione B456; l-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7jpyrimidin-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)ethyl)piperi din- l-yl)-2-chlorophenyl)- dihydropyrimidine-2,4(177,377)-dione B457; l-(5-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-2-chlorophenyl)- dihydropyrimidine-2,4(177,377)-dione B458; l-(5-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-2-fluorophenyl)- dihydropyrimidine-2,4( 177,377)-dione B459; l-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7jpyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-2-fluorophenyl)- dihydropyrimidine-2,4(177,377)-dione B460; l-(5-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-2-methylphenyl)- dihydropyrimidine-2, 4(177, 3 / / )-dione B461; l-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)ethyl)piperi din- l-yl)-2-methylphenyl)- dihydropyrimidine-2,4( 177,377)-dione B462; l-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7jpyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-2-chloro-6-methyl- phenyl)dihydropyrimidine-2,4(177,377)-dione B463; l-(5-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-<)xo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-4-chloro-2-methyl- phenyl)dihydropyrimidine-2,4(177,377)-dione B464; l-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-^pyrimidin-2-yl)amino)pyri din-3 -yl)piperazin-l-yl)ethyl)piperi din- l-yl)-2-chloro-4-methyl- phenyl)dihy dropyrimidine-2,4( 177,377)-dione B465; l-(3-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-4-chloro-2-methyl- phenyl)dihydropyrimidine-2,4( 177,377)-dione B466; l-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-2-chlorophenyl)- dihydropyrimidine-2,4(177,377)-dione B467; l-(4-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l -yl)ethyl)piperazin-l-yl)-2-chlorophenyl)- dihydropyrimidine-2, 4(177, 377)-dione B468; l-(4-(4-(2-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyriniidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)ethyl)piperazin-l -yl)phenyl)dihydro- pyrimidine-2, 4(177, 377)-dione B469; l-(3-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)piperidin-l-yl)phenyl)dihydro- pyrimidine-2, 4(177, 377)-dione B470, l-(3-(4-((3-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t7|pyrimidin-2-yl)amino)pyridin-3-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl)piperidin-l-yl)- phenyl)dihydropyrimidine-2, 4(177, 377)-dione B471; l-(4-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazetidin-3-yl)ethyl)-2-chloro- phenyl)dihydropyrimidine-2,4( 17 / ,377)-dione B472;3-(6-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t7|- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)-2-oxoethoxy)-l-methyl-177-indazol-3-yl)- piperidine-2, 6-dione B501;3-(7-(2-(4-(3-((4-((6-(difluoro-methyl)-8-((lJ?,25)-2-hydroxy-2-methylcyclo- pentyl)-7-oxo-7,8-dihydropyrido[2,3-< / |pyrimidin-2-yl)amino)piperidin-l-yl)sulfonyl)propyl)- piperazin- 1 -yl)-2-oxoethoxy)- 1 -methyl- 177-indazol-3-yl)piperidine-2, 6-dione B502;3-(6-(4-(l-(6-((6-acetyl-8-cyclo-pentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7j- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-l-methyl-177-indazol-3-yl)- piperidine-2, 6-dione B503;3-(6-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazetidin-3-yl)ethyl)-l-methyl-177-indazol -3 -y l)piperi dine-2, 6-dione B504;3-(7-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-6 / j- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-l-methyl-lJ7-indazol-3-yl)-3- methylpiperidine-2, 6-dione B505;3-(7-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazetidin-3-y!)ethyl)-l-methyl-l / / - indazol-3-yl)piperi dine-2, 6-dione B506;3-(6-(4-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)piperidin-l-yl)-l-methyl-l / / -indazol-3-yl)- piperidine-2, 6-dione B507;3-(6-(4-(2-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)ethyl)piperazin-l-yl)-l-methyl-l / / -indazol- 3 -yl)piperi dine-2, 6-dione B508;(5)-3-(6-(4-(2-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2, 3 -< / ]pyrimidin-2-yl)amino)pyri din-3 -yl)piperidin-4-yl)ethyl)piperazin-l-yl)-l -methyl- 1 / 7- indazol-3-yl)-3 -methylpiperidine-2, 6-dione B509;(7?)-3-(6-(4-(2-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3 -< / jpyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)ethyl)piperazin-l-yl)-l -methyl- 1 / 7- indazol-3-yl)-3-methylpiperidine-2, 6-dione B510;3-(6-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-l-methyl-l / / -indazol- 3 -yl)piperi dine-2, 6-dione B511; l-(7-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]-pyrimidin-2-yl)amino)pyri din-3 -yl)piperazin- 1 -y l)ethy Ijpiperidin- 1 -yl)- 1 -methyl- 1 / f-indazol- 3-yl)dihydropyrimidine-2,4(17 / ,3 / / )-dione B551, l-(6-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethyl)piperidin-l-yl)-l -methyl- 1 / f-indazol- 3 -yl)dihydropyrimi dine-2, 4(1 / 7, 3 / / )-dione B552; l-(7-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7|- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-l-methyl-l / 7-indazol-3-yl)- dihydropyrimidine-2,4(l / 7,3 / 7)-dione B553;l-(6-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t7J- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-l-methyl-177-indazol-3-yl)- dihydropyrimidine-2, 4(177, 377)-dione B554; l-(6-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t / ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-5-fluoro-l-methyl-177-indazol- 3-yl)dihydropyrimidine-2, 4(177, 377)-dione B555; l-(6-(4-(] -(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-7-fluoro-l-methyl-177-indazol- 3-yl)dihydropyrimidine-2, 4(177, 377)-dione B556; l-(7-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-t7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-5-fluoro-l-methyl-177-indazol- 3-yl)dihydropyrimidine-2, 4(177, 377)-dione B557; l-(6-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-5-chloro-l-methyl-177-indazol- 3-yl)dihydropyrimidine-2, 4(177, 377)-dione B558; l-(6-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-7-chloro-l-methyl-l / 7-indazol- 3-yl)dihydropyrimidine-2, 4(177, 377)-dione B559; l-(7-(4-( l-(6-((6-acetyl-8-cycloperityl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-(7]- pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)piperazin-l-yl)-5-chloro-l-methyl-177-indazol- 3-yl)dihydropyrimidine-2, 4(177, 377)-dione B560,(LS)-l-(7-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido-[2,3 -<7]pyrimidin-2-yl)amino)pyri din-3 -yl)piperidin-4-yl)-2-methy Ipiperazin- 1 -yl)- 1 -methyl- 177- indazol-3-yl)dihydropyrimidine-2,4(177,377)-dione B561;(77)-l-(7-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-tZ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-2-methylpiperazin-l-yl)-l-methyl-177- indazol-3-yl)dihydropyrimidine-2,4( l / / ,377)-dione B562;(7?)-l -(7-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido-[2, 3 -<7]pyrimidin-2-yl)amino)pyri din-3 -yl)piperidin-4-yl)-3-methylpiperazin-l-yl)-l -methyl- 177- indazol-3-yl)dihydropyrimidine-2, 4(177, 37 / )-dione B563; l-(6-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazetidin-3-yl)ethyl)-l-methyl-l / 7- indazol-3-yl)dihydropyrimidine-2,4(l / / ,3 / / )-dione B564; l-(7-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-< / ]- pyrimidin-2-yl)amino)pyri din-3 -yl)piperidin-4-yl)piperazin-l-yl)-6-chl oro-1 -methyl- l / / -indazol- 3-yl)dihydropyrimidine-2, 4(177, 3J7)-dione B566; l-(7-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3 -y l)piperidin - l-yl)methyl)-4-fluoropiperidin- 1 -yl)- 1 -methyl- l / / -indazol-3-yl)dihydropyrimidine-2,4(l / 7,377)-dione B567;(5)-l-(7-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-c / ]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-methylpiperazin-l-yl)-l-methy{-l / 7- indazol-3-yl)dihydropyrimidine-2,4(l / 7,3Z7)-dione B568; l-(7-(2-(l-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperidin-4-yl)-3-fluoroazetidin-3-yl)ethyl)-l-methyl-177- indazol-3-yl)dihydropyrimidine-2,4( 177,377)-di one B569; l-(6-(2-(r-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- r / |pyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoro-[l,4'-bipiperidin]-4-yl)ethyl)-l-methyl-177- indazol-3-yl)dihydropyrimidine-2, 4(177, 3 / / )-dione B570; l-(7-(2-(l'-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)-4-fluoro-[l ,4'-bipiperidin]-4-yl)ethyl)-l-methyl-l / 7- indazol-3-yl)dihydropyrimidine-2,4(177,3 / 7)-dione B571; l-(7-(4-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-<7]- pyrimidin-2-yl)amino)pyri din-3 -yl)piperidin-4-yl)piperazin-l-yl)-4-chl oro-1 -methyl- 1 / 7-indazol- 3-yl)dihydropyrimidine-2, 4(177, 377)-dione B572; l-(6-(4-(2-(l-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / ]pyrimidin-2-yl)amino)pyri din-3 -yl)piperidin-4-yl)ethyl)piperazin- 1 -yl)- 1 -methyl- 1 / 7-indazol- 3-yl)dihydropyrimidine-2, 4(177, 377)-dione B573, l-(6-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin- 1 -yl)ethyl)piperidin- 1 -yl)-l -methyl- 177-indazol- 3-yl)dihydropyrimidine-2, 4(1 / 7, 377)-dione B574; l-(6-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)methyl)piperidin-l-yl)-l -methyl- 177-indazol-3-yl)dihydropyrimidine-2, 4(177, 3 / 7)-dione B575;3-(5-(l-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- t / jpyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)-2-oxoethyl)piperidin-4-yl)-6-fluoro-l- oxoisoindolin-2-yl)piperidine-2, 6-dione B601;3-(4-((2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3- <7]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)-2-oxoethyl)amino)-l-oxoisoindolin-2-yl)- piperidine-2, 6-dione B602;4-((2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]- pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)-2-oxoethyl)amino)-2-(2,6-dioxopiperi din-3 - yl)isoindoline-l, 3-dione B603; or3-(5-(l-(4-(2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido- [2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-l-yl)ethoxy)benzyl)piperidin-4-yl)-l-oxo- isoindolin-2-yl)piperidine-2, 6-dione B604; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.

170. A pharmaceutical composition comprising the compound of any one of claims 1 to 169, or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof; and a pharmaceutically acceptable excipient.

171. The pharmaceutical composition of claim 170, wherein the composition is in single dosage form.

172. The pharmaceutical composition of claim 170 or 171, wherein the composition is in an oral, parenteral, or intravenous dosage form.

173. The pharmaceutical composition of any one of claims 170 to 172, wherein the composition is formulated in an oral dosage form.

174. The pharmaceutical composition of claim 173, wherein the oral dosage form is atablet or capsule.

175. A method of treating, preventing, or ameliorating one or more symptoms of a disorder, disease, or condition mediated by a CDK in a subject, comprising administering to the subject in need thereof a therapeutically effective amount of a compound of any one of claims 1 to 169 or a pharmaceutical composition of any one of claims 170 to 174.

176. The method of claim 175, wherein the disorder, disease, or condition mediated by the CDK is mediated by CDK2, CDK4, and / or CDK6.

177. The method of claim 175 or 176, wherein the disorder, disease, or condition mediated by the CDK is a proliferative disease.

178. A method of treating, preventing, or ameliorating one or more symptoms of a proliferative disease in a subject, comprising administering to the subject in need thereof a therapeutically effective amount of a compound of any one of claims 1 to 169 or a pharmaceutical composition of any one of claims 170 to 174.

179. The method of claim 177 or 178, wherein the proliferative disease is cancer.

180. The method of any one of claims 175 to 179, wherein the subject is a human.181 . A method of inhibiting the growth of a cell, comprising contacting the cell with an effective amount of a compound of any one of claims 1 to 169 or a pharmaceutical composition of any one of claims 170 to 174.

182. The method of claim 181 , wherein the cell is a cancerous cell.

183. A method of inducing degradation of a CDK, comprising contacting the CDK with an effective amount of a compound of any one of claims 1 to 169 or a pharmaceutical composition of any one of claims 170 to 174184. The method of claim 183, wherein the CDK is CDK2, CDK4, and / or CDK6.

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