Bifunctional compounds for degrading aurora kinase via ubiquitin proteosome pathway

Abstract

Compounds (I), compositions, and methods for use in degrading Aurora kinase are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo. Also disclosed are pharmaceutical compositions comprising Aurora kinase degraders, as well as methods for treating cancer using Aurora kinase degraders.

Description

Attorney Docket No.: 121843.00323 NU-3800 PCT BIFUNCTIONAL COMPOUNDS FOR DEGRADING AURORA KINASE VIA UBIQUITIN PROTEOSOME PATHWAY CROSS REFERENCE

[0001] This patent application claims the benefit under 35 U.S.C. § 119 of U.S. Provisional Patent Application No.63 / 673,643, filed July 19, 2024, the contents of which are incorporated herein by reference in their entirety. FIELD

[0002] This disclosure provides novel bifunctional compounds for proteolytically degrading targeted protein kinase Aurora and methods for treating diseases modulated by Aurora. BACKGROUND

[0003] The family of Aurora kinases (e.g., Aurora-A, -B, and -C) are essential for cell cycle progression. Dysregulation of Aurora kinases, for example Aurora-A, causes overexpression of Aurora-A in cancer. Thus, Aurora kinases are a promising target for therapies for treating several inflammatory, autoimmune, and proliferative diseases and disorders via proteolysis targeting chimeric compounds (PROTACs).

[0004] Many tumors are often driven by deregulated cell cycle control which results in high replication stress, chromosomal instability, and dependence on mitotic fidelity. These tumors rely heavily on precise timing of mitotic entry and exit to survive accumulated DNA damage. Aurora A kinase, a critical regulator of centrosome maturation, spindle assembly, and chromosome alignment, becomes an essential gatekeeper for maintaining this mitotic fidelity. Inhibiting or degrading Aurora A (i.e., rather than merely inhibiting it) could result in a more sustained and irreversible disruption of this machinery, particularly for tumor cells that are already under replicative stress or overexpress Aurora A. Existing therapies inhibiting Aurora A or Aurora B, or dual inhibition of Aurora A and B, disrupt chromosome segregation but don’t degrade or eliminate the protein, which frequently leads to adaptive responses and partial kinase reactivation, which may persist across cell divisions without inducing efficient cell death. This in turn can contribute to tumor heterogeneity and therapeutic resistance, undermining long-term treatment efficacy.

[0005] In contrast, selective and efficient degradation of Aurora A would induce a robust mitotic arrest that often transitions into apoptosis or mitotic cell death, a more desirable - 1 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT therapeutic outcome. Mechanistically, Aurora A controls centrosome maturation and spindle assembly checkpoint fidelity—functions that, when disrupted, generate intolerable mitotic stress in proliferating cancer cells. Importantly, clinical evidence supports the need for a specific and effective Aurora A degrader. Aurora A, Aurora B, and dual Aurora A / B inhibitors have been associated with dose-limiting hematologic toxicities, including neutropenia and bone marrow suppression. This could be due to lack of specificity of Aurora A inhibition and Aurora B’s essential role in cytokinesis in normal proliferating tissues. In contrast, an Aurora A-selective degrader(s), such as those described herein, demonstrate effective apoptosis, reduced myelosuppression, and shrinking of tumors, as evident in the Examples herein.

[0006] Beyond its canonical mitotic functions, Aurora A has been shown to have a non- catalytic oncogenic role in stabilizing N-Myc. This role of Aurora A, particularly in cancers where MYCN amplification is a primary driver of tumor biology, makes targeting of Aurora A through degradation a viable therapeutic avenue in any cancers where levels of MYCN could be at least partial drivers of tumorigenicity. For example, in neuroblastoma and subsets of small cell lung cancer (SCLC), Aurora A directly binds to N-Myc and protects it from degradation by preventing recognition by the E3 ligase. This scaffold-like interaction is kinase-independent and is not disrupted by ATP-competitive Aurora A inhibitors. See, Otto et al., Stabilization of N-Myc is a Critical Function of Aurora A in Human Neuroblastoma, Cancer Cell, 2009.

[0007] The specific and effective Aurora A degraders disclosed herein can eliminate the entire protein, abolishing both catalytic activity and the scaffolding function required for N- Myc stabilization. The data presented herein shows tumor regression following Aurora A degradation in N-Myc-amplified neuroblastoma, and SCLC, for example, where inhibitors have only produced modest effects. SUMMARY

[0008] Provided herein are compounds capable of binding, inhibiting, and / or degrading Aurora kinases. The compounds are useful for the treatment or prevention of inflammatory, autoimmune, and proliferative diseases and disorders in a subject in need thereof. In certain embodiments, the compounds described herein include an Aurora hook bound to a linker further bound to a ubiquitin ligase harness.

[0009] Disclosed herein is a compound represented by Formula I - 2 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCTpharmaceutically acceptable salt thereof or stereoisomer thereof,an unsubstituted or substituted 5- or 6-membered aryl or heteroaryl wherein one or more substituents are independently selected from alkyl or halogen; R1is, independently, hydrogen or halogen; R3is hydrogen or alkyl; X2is -N(H)-, oxygen, or sulfur; X3is alkylene; heteroalkylene; cycloalkylene; arylene; heteroarylene; unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, haloalkyl, halogen, acyl, amino, -CN, hydroxyl, nitro, -C(O)-, -SO2-, hydroxyalkyl, alkoxyalkyl, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen, alkyl, or alkenyl; unsubstituted or substituted -S(O)2-heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen, acyl, amino, -CN, hydroxyl, nitro, hydroxyalkyl, -C(O)-, alkoxyalkyl, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen, alkyl, or alkenyl;; ; -C(O)-; -C(O)N(H)-; -N(H)-; -O-; or -S(O)2-; X4is carbon or nitrogen, wherein when X4is nitrogen then the R1bound to X4is absent; Z1and Z2are independently carbon, nitrogen, -N(H)-, oxygen, or sulfur wherein the ring containing Z1and Z2is aromatic; Z3is an unsubstituted or substituted 5- or 6-membered aryl or heteroaryl wherein one or more substituents are independently selected from alkyl or halogen; or; R2is selected from - 3 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCTlinker; is a ubiquitin ligase targeting moiety (UTM) having the following chemical formulawherein X5is carbon or nitrogen; R4is absent, -N(R4a)-, oxygen, sulfur, or -N(R4a)C(O)- wherein R4ais hydrogen or alkyl; R5is unsubstituted or substituted arylene or heteroarylene wherein one or more substituents are independently selected from the group consisting of halogen and alkyl; R6is absent, -N(R6a)-, oxygen, or sulfur wherein R6ais hydrogen or alkyl; R7is absent; unsubstituted or substituted cycloalkylene or heterocycloalkylene wherein one or more substituents are independently selected from the group consisting of halogen and alkyl; an unsubstituted or substituted five- to fifteen- membered spiro heterocycloalkylene; or an unsubstituted or substituted four- to fourteen- membered fused heterocycloalkylene; R8is absent, alkylene, -C(O)-, -N(R8a)-, oxygen, or sulfur wherein R8ais hydrogen or alkyl; and each n is independently zero, one, or two.

[0010] Disclosed herein is a compound represented by Formulaa pharmaceutically acceptable salt thereof or stereoisomer thereof, wherein X1is halogen; Y1substituted 5- or 6-membered aryl or heteroaryl wherein one or more substituents are independently selected from alkyl or halogen; R1is, independently, hydrogen or halogen; R3- 4 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT is hydrogen or alkyl; X2is -N(H)-, oxygen, or sulfur; X3is alkylene; heteroalkylene; cycloalkylene; arylene; heteroarylene; unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, haloalkyl, halogen, acyl, amino, -CN, hydroxyl, nitro, -C(O)-, -SO2-, hydroxyalkyl, alkoxyalkyl, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen, alkyl, or alkenyl; unsubstituted or substituted -S(O)2-heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen, acyl, amino, -CN, hydroxyl, nitro, hydroxyalkyl, -C(O)-, alkoxyalkyl, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen, alkyl, or alkenyl;carbon or nitrogen, wherein when X4is nitrogen then the R1bound to X4is absent; Z1and Z2are independently carbon, nitrogen, -N(H)-, oxygen, or sulfur wherein the ring containing Z1and Z2is aromatic; Z3is an unsubstituted or substituted 5- or 6-membered aryl or heteroaryl wherein one or more substituents are independently selected from alkyl or halogen; orR2ischemical formulawherein X5is carbon or nitrogen; R4is absent, -N(R4a)-, - 5 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT oxygen, sulfur, or -N(R4a)C(O)- wherein R4ais hydrogen or alkyl; R5is unsubstituted or substituted arylene or heteroarylene wherein one or more substituents are independently selected from the group consisting of halogen and alkyl; R6is absent, -N(R6a)-, oxygen, or sulfur wherein R6ais hydrogen or alkyl; R7is absent; unsubstituted or substituted cycloalkylene or heterocycloalkylene wherein one or more substituents are independently selected from the group consisting of halogen and alkyl; an unsubstituted or substituted five- to fifteen- membered spiro heterocycloalkylene; or an unsubstituted or substituted four- to fourteen- membered fused heterocycloalkylene; and R8is absent, alkylene, -C(O)-, -N(R8a)-, oxygen, or sulfur wherein R8ais hydrogen or alkyl.

[0011] Disclosed herein is a compound represented by Formula A, B, C, D, E, F, G, or H- 6 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCTa pharmaceutically acceptable salt thereof or stereoisomer thereof, wherein R1is, independently, hydrogen or halogen; R2is selected from, ,hydrogen or alkyl; X1is halogen; X2is -N(H)-, oxygen, or sulfur; X3is alkylene; heteroalkylene; cycloalkylene; arylene; heteroarylene; unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, haloalkyl, halogen, acyl, amino, -CN, hydroxyl, nitro, -C(O)-, -SO2-, hydroxyalkyl, alkoxyalkyl, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen, alkyl, or alkenyl; unsubstituted or substituted -S(O)2-heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen, acyl, amino, -CN, hydroxyl, nitro, hydroxyalkyl, -C(O)-, alkoxyalkyl, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen, alkyl, or alkenyl;; ; -C(O)-; -C(O)N(H)-; -N(H)-; -O-; or -S(O)2-; X4is carbon or nitrogen, wherein when X4is nitrogen then the R1bound to X4is absent; L is a bond or a linker;is a ubiquitin ligase targeting - 7 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT moiety (UTM) having the following chemical formulawherein X5is carbon or nitrogen; R4is absent, -N(R4a)-, oxygen, sulfur, or -N(R4a)C(O)- wherein R4ais hydrogen or alkyl; R5is unsubstituted or substituted arylene or heteroarylene wherein one or more substituents are independently selected from the group consisting of halogen and alkyl; R6is absent, -N(R6a)-, oxygen, or sulfur wherein R6ais hydrogen or alkyl; R7is absent; unsubstituted or substituted cycloalkylene or heterocycloalkylene wherein one or more substituents are independently selected from the group consisting of halogen and alkyl; an unsubstituted or substituted five- to fifteen-membered spiro heterocycloalkylene; or an unsubstituted or substituted four- to fourteen-membered fused heterocycloalkylene; R8is absent, alkylene, -C(O)-, -N(R8a)-, oxygen, or sulfur wherein R8ais hydrogen or alkyl; and each n is independently zero, one, or two.

[0012] Disclosed herein is a compound represented by the following formulaor a pharmaceutically acceptable salt thereof or stereoisomer thereof, whereinis an unsubstituted or substituted cycloalkyl, heterocycloalkyl, aryl, or heteroaryl wherein one or more substituents are independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen, acyl, amino, -CN, hydroxyl, nitro, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen or alkyl; R1is an unsubstituted or substituted aryl or heteroaryl wherein one or more substituents are independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen, acyl, amino, -CN, hydroxyl, nitro, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102- 8 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT are, independently, hydrogen or alkyl; R2is hydrogen or alkyl; X1is an unsubstituted or substituted heterocycloalkylene wherein one or more substituents are independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen, acyl, amino, -CN, hydroxyl, nitro, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen or alkyl; L is a bond or a linker; is a ubiquitin ligase targeting moiety (UTM) having the followingchemical formula wherein R3is arylene or heteroarylene; R4is absent or heterocycloalkylene; and R5is absent, alkylene, or -C(O)-.

[0013] Disclosed herein is a pharmaceutical composition comprising an effective amount of any compound(s) described herein in combination with a pharmaceutically acceptable carrier, additive, or excipient; and optionally in further combination with an additional biologically active agent.

[0014] Disclosed herein is a method of treating cancer in a patient in need thereof, wherein dysregulated protein activity is responsible for the cancer, the method comprising administering to the patient an effective amount of any compound(s), any pharmaceutical composition, or any composition described herein, wherein the compound modulates the amount or activity of the protein in the patient.

[0015] Disclosed herein is a process for making the compound(s) of Formula A, B, C, D, or E.

[0016] Disclosed herein is a process for making the compound(s) of the following formula.

[0017] Disclosed herein is a drug-antibody conjugate including an antibody or an antigen binding fragment thereof covalently linked to one or more compounds described herein. BRIEF DESCRIPTION OF THE DRAWING - 9 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0018] FIG.1 shows the cooperativity of the ternary complex induced by compound 280 between AURKA and CRBN.

[0019] FIG.2 shows that compound 280 degrades AURKA.

[0020] FIG.3 shows that compound 280 is selective for AURORA A.

[0021] FIG.4 shows that compound 280 degrades AURKA and reduces MYCN levels in neuroblastoma in vitro.

[0022] FIG. 5 shows that compound 280 causes substantial degradation of AURKA benchmarked to an AURKA inhibitor.

[0023] FIG. 6 shows that compound 280 induces DNA damage and apoptosis at twenty- four hours in SK-N-BE(2) neuroblastoma cell line in vitro.

[0024] FIG.7 shows that compound 280 induces DNA damage and apoptosis in SCLC cell lines in vitro.

[0025] FIG.8 shows that compound 280 has antiproliferative activity across several cancer cell lines.

[0026] FIG.9 shows gene expression-based stratification and correlative pathway analysis of compound 280.

[0027] FIG. 10 shows that compound 280 has high oral bioavailability and is tissue and brain penetrant.

[0028] FIG. 11 shows that compound 280 rapidly degrades AURKA in the IMR32 neuroblastoma tumor model.

[0029] FIG. 12 shows that after three days of administration, compound 280 leads to prolonged suppression of P-AURKA kinase and reduced levels of MYCN.

[0030] FIG.13 shows that after three days of administration, compound 280 induces DNA damage response, and G2 / M arrest in the IMR32 tumor model.

[0031] FIG. 14 shows that compound 280 results in tumor volume suppression and improved survival in vivo in neuroblastoma.

[0032] FIG. 15 shows that after three days of administration, compound 280 leads to prolonged suppression of P-AURKA kinase, reduced levels of MYC, increased DNA damage, and apoptosis in SCLC in vivo.

[0033] FIG. 16 shows that compounds 280 results in tumor volume suppression and improved survival in vivo in SCLC. - 10 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT DETAILED DESCRIPTION

[0034] For purposes herein, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed. Additionally, general principles of organic chemistry are described in “Organic Chemistry,” Thomas Sorrell, University Science Books, Sausalito: 1999, and “March’s Advanced Organic Chemistry,” 5th Ed., Ed.: Smith, M.B. and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are hereby incorporated herein by reference. Definitions

[0035] When referring to the compounds and conjugates provided herein, the following terms have the following meanings unless indicated otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art. In the event that there is a plurality of definitions for a term herein, those in this section prevail unless stated otherwise.

[0036] As used herein, the term “combinations thereof” includes every possible combination of elements to which the term refers to.

[0037] As used herein, an “effective amount” of an agent disclosed herein is an amount sufficient to carry out a specifically stated purpose. An “effective amount” may be determined empirically and in a routine manner in relation to the stated purpose. An “effective amount” or an “amount sufficient” of an agent is that amount adequate to produce a desired biological effect, such as a beneficial result, including a beneficial clinical result. In some embodiments, the term “effective amount” refers to an amount of an agent effective to “treat” a disease or disorder in an individual (e.g., a mammal such as a human).

[0038] As used herein, a “protecting group” refers to a chemical moiety or chemical functionality that is introduced into a molecule by chemical modification of an existing chemical functional group in order to obtain chemoselectivity in a subsequent chemical reaction. Standard protecting groups are known in the relevant art and are provided in Wuts and Greene: “Greene’s Protective Groups in Organic Synthesis,” 4th Ed, Wuts, P.G.M. and Greene, T.W., Wiley-Interscience, New York: 2006.

[0039] As used herein, the terms “pharmaceutical formulation” and “pharmaceutical composition” refer to preparations that are in such form as to permit the biological activity of the active ingredient to be effective, and that contain no additional components that are - 11 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT unacceptably toxic to an individual (e.g., a mammal such as a human) to which the formulation or composition would be administered. Such formulations or compositions may be sterile.

[0040] As used herein, “excipients” include pharmaceutically acceptable excipients, carriers, vehicles, or stabilizers that are nontoxic to the cell or mammal being exposed thereto at the dosages and concentrations employed. Often the physiologically acceptable excipient is an aqueous pH buffered solution.

[0041] Reference to a compound as described in a pharmaceutical composition, or to a compound as described in a claim to a pharmaceutical composition, refers to the compound described by the formula recited in the pharmaceutical composition, without the other elements of the pharmaceutical composition, that is, without carriers, excipients, etc.

[0042] As used herein, the terms “treating” or “treatment” of a disease refer to executing a protocol, which may include administering one or more therapeutic agents to an individual (e.g., human or otherwise), in an effort to obtain beneficial or desired results in the individual, including clinical results. Beneficial or desired clinical results include, but are not limited to, alleviation or amelioration of one or more symptoms, diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, preventing spread of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total). “Treatment” can also mean prolonging survival as compared to expected survival of an individual not receiving treatment. Further, “treating” and “treatment” may occur by administration of one dose of a therapeutic agent(s), or may occur upon administration of a series of doses of a therapeutic agent or therapeutic agents. “Treating” or “treatment” does not require complete alleviation of signs or symptoms, and does not require a cure. “Treatment” also can refer to clinical intervention, such as administering one or more therapeutic agents to an individual, designed to alter the natural course of the individual or cell being treated (i.e., to alter the course of the individual or cell that would occur in the absence of the clinical intervention). The term “therapeutic agent” can refer to a Aurora kinase inhibitor or degrader.

[0043] As used herein, an “individual” or a “subject” is a mammal. A “mammal” for purposes of treatment includes humans; non-human primates; domestic and farm animals; and zoo, sports, or pet animals, such as dogs, horses, rabbits, cattle, pigs, hamsters, gerbils, mice, ferrets, rats, cats, etc. In some embodiments, the individual or subject is human.

[0044] As used herein, “proliferation” refers to the proliferation of a cell. Increased proliferation encompasses the production of a greater number of cells relative to a baseline value. Decreased proliferation encompasses the production of a reduced number of cells - 12 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT relative to a baseline value. In some embodiments, the cell is a cancer cell and reduced proliferation is desired.

[0045] “Alkyl” as used herein refers to a saturated linear (i.e., unbranched) or branched univalent hydrocarbon chain or combination thereof. Particular alkyl groups include those having a designated number of carbon atoms, for example, an alkyl group having one ot twenty carbon atoms (e.g., “C1-C20 alkyl”), having one to ten carbon atoms (e.g., “C1-C10” alkyl), having one to eight carbon atoms (e.g., “C1-C8 alkyl”), having one to six carbon atoms (e.g., “C1-C6alkyl”), having two to six carbon atoms (e.g., “C2-C6alkyl”), or having one to four carbon atoms (e.g., “C1-C4alkyl”). Examples of alkyl group embodiments include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec- butyl, homologs and isomers of, for example, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like. An alkyl group can be substituted (i.e., optionally substituted) with one or more substituents including, but without limitation halo; phospho; cycloalkyl or cycloalkenyl); heterocycloalkyl or heterocycloalkenyl); aryl; heteroaryl; alkoxy; aroyl; heteroaroyl; acyl; nitro; cyano; amido; amino; sulfonyl (e.g., alkyl-SO2-, cycloalkyl-SO2-, or aryl-SO2-); sulfinyl; sulfanyl; sulfoxy; urea; thiourea; sulfamoyl; sulfamide; oxo or carbonyl or -C(O)-; carboxy or COOR wherein R is hydrogen or alkyl; carbamoyl; aryloxy; heteroaryloxy, aralkyloxy, heteroarylalkoxy, alkoxycarbonyl, or hydroxy.

[0046] “Alkenyl” as used herein refers to an unsaturated linear (i.e., unbranched) or branched univalent hydrocarbon chain or combination thereof, having at least one site of olefinic unsaturation (i.e., having at least one moiety of the formula C=C). Particular alkenyl groups inlcude those having a designated number of carbon atoms, for example, an alkenyl group having two to twenty carbon atoms (e.g., “C2-C20 alkenyl”), having two to ten carbon atoms (e.g., “C2-C10” alkenyl), having two two eight carbon atoms (e.g., “C2-C8 alkenyl”), having two to six carbon atoms (e.g., “C2-C6alkenyl”), or having two to four carbon atoms (a “C2-C4alkenyl”). The alkenyl group may be in “cis-” or “trans-” configurations or, alternatively, in “E-” or “Z-” configurations. Examples of alkenyl groups include, but are not limited to, groups such as ethenyl (or vinyl), prop-1-enyl, prop-2-enyl (or allyl), 2-methylprop-1-enyl, but-1-enyl, but-2-enyl, but-3-enyl, buta-1,3-dienyl, 2-methylbuta-1,3-dienyl, homologs, and isomers thereof, and the like.

[0047] “Alkynyl” as used herein refers to an unsaturated linear (i.e., unbranched) or branched univalent hydrocarbon chain or combination thereof, having at least one site of acetylenic unsaturation (i.e., having at least one moiety of the formula C≡C). Particular alkynyl - 13 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT groups include those having a designated number of carbon atoms, for example, an alkynyl group having two to twenty carbon atoms (e.g., “C2-C20alkynyl”), having two to ten carbon atoms (e.g., “C2-C10 alkynyl”), having two to eight carbon atoms (a “C2-C8 alkynyl”), having two to six carbon atoms (a “C2-C6 alkynyl”), or having two to four carbon atoms (a “C2-C4 alkynyl”). Examples of alkynyl groups include, but are not limited to, groups such as ethynyl (or acetylenyl), prop-1-ynyl, prop-2-ynyl (or propargyl), but-1-ynyl, but-2-ynyl, but-3-ynyl, homologs, and isomers thereof, and the like.

[0048] As used herein, the term “aliphatic” encompasses the terms alkyl, alkenyl, and alkynyl, each of which are optionally substituted as set forth elsewhere herein.

[0049] As used herein, “heteroalkyl” refers to an alkyl in which one or more carbon atoms are replaced by a heteroatom(s). As used herein, “heteroalkenyl” refers to an alkenyl in which one or more carbon atoms are replaced by a heteroatom(s). As used herein, “heteroalkynyl” refers to an alkynyl in which one or more carbon atoms are replaced by a heteroatom(s). Suitable heteroatoms include, but are not limited to, nitrogen (N), oxygen (O), and sulfur (S) atoms. Heteroalkyl, heteroalkenyl, and heteroalkynyl are optionally substituted. Examples of heteroalkyl moieties include, but are not limited to, aminoalkyl, sulfonylalkyl, and sulfinylalkyl. Examples of heteroalkyl moieties also include, but are not limited to, methylamino, methylsulfonyl, and methylsulfinyl. “Heteroalkylene” as used herein refers to divalent heteroalkyl.

[0050] “Alkylene” as used herein refers to the same residues as alkyl, but divalent. Particular alkylene groups are those having one to ten carbon atoms (e.g., “C1-C10 alkylene”), one to nine carbon atoms (e.g., “C1-C9alkylene”), one to eight carbon atoms (e.g., “C1-C8alkylene”), one to seven carbon atoms (e.g., “C1-C7 alkylene”), one to six carbon atoms (e.g., “C1-C6 alkylene”), one to five carbon atoms (a “C1-C5 alkylene”), one to four carbon atoms (a “C1-C4alkylene”), one to three carbon atoms (a “C1-C3alkylene”), two carbons atoms (e.g., - CH2CH2-), or one carbon atom (e.g., methylene or -CH2-). Examples of alkylene groups include, but are not limited to, groups such as methylene (-CH2-), -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, and the like.

[0051] “Cycloalkyl” as used herein refers to non-aromatic, saturated or unsaturated, cyclic univalent hydrocarbon structures. Particular cycloalkyl groups include those having a designated number of annular (i.e., ring) carbon atoms, for example, a cycloalkyl group having from three two fifteen annular carbon atoms (e.g., “C3-C15cycloalkyl”). A particular cycloalkyl is a cyclic hydrocarbon having from three to eight annular carbon atoms (e.g., “C3-C8- 14 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT cycloalkyl”), or having three to six annular carbon atoms (e.g., “C3-C6 cycloalkyl”). Cycloalkyl can consist of one ring, such as cyclohexyl, or multiple rings but excludes aromatic (e.g., aryl) groups. A cycloalkyl comprising more than one ring may be fused, spiro, or bridged, or combinations thereof. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, 1- cyclohexenyl, 3-cyclohexenyl, cycloheptyl, norbornyl, cubyl, octahydro-indenyl, decahydro-naphthyl, bicyclo[3.2.1]octyl, bicyclo[2.2.2]octyl, bicyclo[3.3.1]nonyl, bicyclo[3.3.2]decyl, or spiro[3.3]heptanyl, and the like.

[0052] “Cycloalkenyl” as used herein refers to a non-aromatic carbocyclic ring of three to ten (e.g., four to eight) carbon atoms having one or more double bonds. Examples of cycloalkenyl groups include cyclopentenyl, 1,4-cyclohexa-di-enyl, cycloheptenyl, cyclooctenyl, hexahydro-indenyl, octahydro-naphthyl, cyclohexenyl, bicyclo[2.2.2]octenyl, or bicyclo[3.3.1]nonenyl.

[0053] “Cycloalkylene” as used herein refers to the same residues as cycloalkyl, but divalent (i.e., in contrast to being univalent). Particular cycloalkylene groups are those having three to fifteen annular carbon atoms (e.g., “C3-C15cycloalkylene”), having from three to eight annular carbon atoms (e.g., “C3-C8 cycloalkylene”), or having three to six annular carbon atoms (e.g., “C3-C6 cycloalkylene”). Examples of cycloalkylene groups include, but are not limited to, cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene ,2-cyclohexenylene, 1,3-cyclohexenylene, 1,4-cyclohexenylene, cycloheptylene, norbornylene, and the like.

[0054] “Aryl” as used herein refers to an aromatic carbocyclic group having a single ring (e.g., phenyl), or multiple condensed rings (e.g., naphthyl or anthryl) where one or more of the condensed rings may not be aromatic. Particular aryl groups are those having from six to fourteen annular (i.e., ring) carbon atoms (a “C6-C14aryl”). An aryl group having more than one ring where at least one ring is non-aromatic may be connected to the parent structure at - 15 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT either an aromatic ring position or at a non-aromatic ring position. In one variation, an aryl group having more than one ring where at least one ring is non-aromatic is connected to the parent structure at an aromatic ring position. Examples of aryls include, but are not limited to, groups such as phenyl, naphthyl, 1-naphthyl, 2-naphthyl, 1,2,3,4-tetrahydronaphthalen-6-yl, and the like.

[0055] “Carbocyclyl” or “carbocyclic” refers to an aromatic or non-aromatic univalent cyclic group in which all of the ring members are carbon atoms, such as cyclohexyl, phenyl, 1,2-dihydronaphthyl, etc.

[0056] “Arylene” as used herein refers to the same residues as aryl, but divalent. Particular arylene groups are those having from six to fourteen annular carbon atoms (e.g., “C6-C14arylene”). Examples of arylene include, but are not limited to, groups such as phenylene, o- phenylene (i.e., 1,2-phenylene), m-phenylene (i.e., 1,3-phenylene), p-phenylene (i.e., 1,4- phenylene), naphthylene, 1,2-naphthylene, 1,3-naphthylene, 1,4-naphthylene, 2,7- naphthylene, 2,6-naphthylene, and the like.

[0057] “Heteroaryl” as used herein refers to an unsaturated aromatic cyclic group having from one to fourteen annular carbon atoms and at least one annular heteroatom, including, but not limited to, heteroatoms such as nitrogen (N), oxygen (O), and sulfur (S). A heteroaryl group may have a single ring (e.g., pyridyl or imidazolyl) or multiple condensed rings (e.g., indolinyl, indolizinyl, indolyl, or quinolinyl) where at least one of the condensed rings is aromatic. Particular heteroaryl groups are 5- to 14-membered rings having one to twelve annular carbon atoms and ons to six annular heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur (e.g., “5- to 14- membered heteroaryl”); 5- to 10-membered rings having one to eight annular carbon atoms and one ot four annular heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur (e.g., “5- to 10- membered heteroaryl”); or 5-, 6-, or 7-membered rings having one to five annular carbon atoms and one to four annular heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur (e.g., “5- to 7- membered heteroaryl”). In one variation, heteroaryl includes monocyclic aromatic 5-, 6-, or 7-membered rings having from one to six annular carbon atoms and one to four annular heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. In another variation, heteroaryl includes polycyclic aromatic rings having from one to twelve annular carbon atoms and one to six annular heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. A heteroaryl - 16 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT group having more than one ring where at least one ring is non-aromatic may be connected to the parent structure at either an aromatic ring position or at a non-aromatic ring position. A heteroaryl group includes a benzofused ring system having two to three rings. For example, a benzofused group includes one or two 4- to 8-membered heterocycloaliphatic moieties (e.g., indolizyl, indolyl, isoindolyl, isoindolinyl-1,3-dione, isoindolinyl-1-one, 3H-indolyl, indolinyl, benzo[b]furyl, benzo[b]thiopheneyl, quinolinyl, or isoquinolinyl). Some examples of heteroaryl are pyridyl, 1H-indazolyl, furyl or furanyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, tetrazolyl, benzofuryl or benzofuranyl, isoquinolinyl, 1-oxoisoquinolin-2(1H)-yl, benzthiazolyl, xanthene, thioxanthene, phenothiazine, dihydroindole, benzo[1,3]dioxole, benzo[b]furyl, benzo[b]thiopheneyl, indazolyl, benzimidazolyl, 3-methyl-2-oxo-2,3-dihydro- 1H-benzo[d]17midazole-1-yl, benzthiazolyl, puryl or purinyl, cinnolyl, quinolyl, quinazolyl, phthalazyl, quinazolyl, quinoxalyl, isoquinolyl, 4H-quinolizyl, benzo-1,2,5-thiadiazolyl, or 1,8-naphthyridyl. Other examples of heteroaryls include 1,2,3,4-tetrahydroisoquinoline and 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine.

[0058] Without limitation, monocyclic heteroaryls include furyl, thiophene-yl, 2H- pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, 1,3,4-thiadiazolyl, pyridyl, pyridazyl, pyrimidyl, pyrazolyl, pyrazyl, or 1,3,5-triazyl. Monocyclic heteroaryls are numbered according to standard chemical nomenclature.

[0059] Without limitation, bicyclic heteroaryls include indolizyl, indolyl, isoindolyl, 3H- indolyl, indolinyl, benzo[b]furyl, benzo[b]thiopheneyl, quinolinyl, isoquinolinyl, indazolyl, benzimidazyl, benzthiazolyl, purinyl, 4H-quinolizyl, quinolyl, isoquinolyl, cinnolyl, phthalazyl, quinazolyl, quinoxalyl, 1,8-naphthyridyl, or pteridyl. Bicyclic heteroaryls are numbered according to standard chemical nomenclature.

[0060] “Heterocyclyl,” “heterocycloalkyl,” “heterocycloalkylene,” and “heterocyclic groups” as used herein refer to non-aromatic saturated or partially unsaturated cyclic groups having the number of atoms and heteroatoms as specified, or if no number of atoms or heteroatoms is specified, having at least three annular atoms, from one to fourteen annular carbon atoms, and at least one annular heteroatom, including, but not limited to, heteroatoms such as nitrogen, oxygen, and sulfur. Heterocycloalkylenes are divalent akin to cycloalkylenes above. A heterocyclic group may have a single ring (e.g., tetrahydrothiophenyl, oxazolidinyl) or multiple condensed rings (e.g., decahydroquinolinyl, octahydrobenzo[d]oxazolyl). Multiple condensed rings include, but are not limited to, bicyclic, tricyclic, and quadracylic rings, as well as bridged or spirocyclic ring systems. Non-limiting examples of a heterocycloalkyl (or - 17 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT a divalent heterocycloalkylene) group include piperidyl or piperidinyl, piperazyl or piperazinyl, tetrahydropyranyl, tetrahydrofuryl or tetrahydrofuranyl, 1,4-dioxolanyl, 1,4-dithianyl, 1,3- dioxolanyl, 1,3-diazepanyl, 1,4-diazepanyl, oxazolidyl or oxazolidinyl, isoxazolidyl or isoxazolidinyl, morpholinyl, thiomorpholinyl, octahydrobenzofuryl or octahydrobenzofuranyl, octahydrochromenyl, octahydrothiochromenyl, octahydroindolyl or octahydroindolinyl, octahydropyrindinyl or octahydro-1H-cyclopenta[x]pyridine where x is b or c, decahydroquinolinyl, octahydrobenzo[b]thiopheneyl, 2-oxa-bicyclo[2.2.2]octyl, 1-aza- bicyclo[2.2.2]octyl, 3-aza-bicyclo[3.2.1]octyl, 3,8-diazabicyclo[3.2.1]octyl, decahydro-2,7- naphthyridine, 2,8-diazaspiro[4.5]decane, 2-azaspiro[3.3]heptane, 2-azaspiro[3.5]nonane, 3- azaspiro[5.5]undecane, 2,7-diazaspiro[3.5]nonane, octahydropyrrolo[3,4-c]pyrrole, octahydro-1H-pyrrolo[3,4-b]pyridine, 2,5-diazabicyclo[2.2.1]heptane, 1-oxa-8- azaspiro[4.5]decane, and 2,6-dioxa-tricyclo[3.3.1.03,7]nonyl. A monocyclic heterocycloalkyl group can be fused with a phenyl moiety to form, for example, tetrahydroisoquinoline, that could be categorized as a heteroaryl as defined elsewhere herein.

[0061] “Heterocycloalkenyl” as used herein refers to a mono- or bicylic (e.g., 5- to 10- membered mono- or bicyclic) non-aromatic ring structure having one or more double bonds, and wherein one or more of the ring atoms is a heteroatom (e.g., nitrogen (N), oxygen (O), or sulfur (S)). Monocyclic and bicyclic heterocycloalkenyls are numbered according to standard chemical nomenclature.

[0062] “Heteroarylene” as used herein refers to the same residues as heteroaryl, but divalent. Particular heteroarylene groups are 5- to 14-membered rings having one ot twelve annular carbon atoms and one to six annular heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur (e.g., “5- to 14- membered heteroarylene”); 5- to 10-membered rings having one to eight annular carbon atoms and one to four annular heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur (e.g., “5- to 10- membered heteroarylene”); or 5-, 6-, or 7-membered rings having one to five annular carbon atoms and one ot four annular heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur (e.g., “5- to 7-membered heteroarylene”). Examples of heteroarylene include, but are not limited to, groups such as pyridylene, benzimidazolylene, benzotriazolylene, benzo[b]thienylene, quinolinylene, indolylene, benzothiazolylene, and the like.

[0063] “Halo” or “halogen” as used herein refers to elements of the Group 17 series having atomic number 9 to 85. Halogen includes fluoro (F), chloro (Cl), bromo (Br), and iodo (I). - 18 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0064] “Haloalkyl,” “haloalkylene,” “haloaryl,” “haloarylene,” “haloheteroaryl,” and similar terms refer to a moiety substituted with at least one halo group. Where a haloalkyl moiety or other halo-substituted moiety is substituted with more than one halogen, it may be referred to by using a prefix corresponding to the number of halogen moieties attached. For example, dihaloaryl, dihaloalkyl, trihaloaryl, trihaloalkyl, etc., refer to aryl and alkyl substituted with two (“di”) or three (“tri”) halo groups, which may be, but are not necessarily, the same halo; thus, for example, the haloaryl group 4-chloro-3-fluorophenyl is within the scope of dihaloaryl. The subset of haloalkyl groups in which each hydrogen (H) of an alkyl group is replaced with a halo group is referred to as a “perhaloalkyl.” A particular perhaloalkyl group is trifluoroalkyl (-CF3). Similarly, “perhaloalkoxy” refers to an alkoxy group in which a halogen takes the place of each hydrogen (H) in the hydrocarbon making up the alkyl moiety of the alkoxy group. An example of a perhaloalkoxy group is trifluoromethoxy (-OCF3). “Haloalkyl” includes monohaloalkyl, dihaloalkyl, trihaloalkyl, perhaloalkyl, and any other number of halo substituents possible on an alkyl group; and similarly for other groups such as haloalkylene, haloaryl, haloarylene, haloheteroaryl, etc.

[0065] “Hydroxyalkyl,” “hydroxyalkylene,” “hydroxyaryl,” “hydroxyarylene,” “hydroxyheteroaryl,” and similar terms refer to a moiety substituted with at least one hydroxyl (OH) group. Where a hydroxyalkyl moiety or other hydroxy-substituted moiety is substituted with more than one hydroxyl, it may be referred to by using a prefix corresponding to the number of hydroxyl moieties attached. For example, dihydroxyaryl, dihydroxyalkyl, trihydroxyaryl, trihydroxyalkyl, etc., refer to aryl and alkyl substituted with two (“di”) or three (“tri”) hydroxyl groups. The subset of hydroxyalkyl groups in which each hydrogen (H) of an alkyl group is replaced with a hydroxyl group is referred to as a “perhydroxyalkyl.” “Hydroxyalkyl” includes monohydroxyalkyl, dihydroxyalkyl, trihydroxyalkyl, perhydroxyalkyl, and any other number of hydroxyl substituents possible on an alkyl group; and similarly for other groups such as hydroxyalkylene, hydroxyaryl, hydroxyarylene, hydroxyheteroaryl, etc.

[0066] “Amino” as used herein refers to the group -NR2 where each R is, for example, independently hydrogen or alkyl.

[0067] As used herein, an “amido” group refers to -N(RX)-C(O)-RYor -C(O)-N(RX)2 when used terminally, and -C(O)-N(RX)- or -N(RX)-C(O)- when used internally, wherein RXand RYcan be alkyl, heteroalkyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl. - 19 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0068] “Oxo,” as used herein, refers to a carbonyl group (e.g., =O or -C(O)-), that is, an oxygen doubly bonded to carbon or another chemical element.

[0069] As used herein, the term “hydroxyl” or “hydroxy” refers to an -OH moiety.

[0070] As used herein, “nitro” refers to -NO2.

[0071] As used herein, “arylalkyl” refers to a monovalent moiety that is a radical of an alkyl compound, wherein the alkyl compound is substituted with an aromatic substituent (i.e., the aromatic compound includes a single bond to an alkyl group and wherein the radical is localized on the alkyl group). An arylalkyl group bonds to the illustrated chemical structure via the alkyl group. An arylalkyl can be represented by the structure ,,, wherein B is an aromatic moiety (e.g., aryl or phenyl). Arylalkyl is optionally substituted (i.e., the aryl group and / or the alkyl group, can be substituted as disclosed herein). Examples of arylalkyl include, but are not limited to, benzyl.

[0072] As used herein, “acyl” refers to -C(O)R where R is alkyl. Acetyl and pivaloyl are examples of acyl groups.

[0073] As used herein, an “aroyl” or “heteroaroyl” refers to an aryl-C(O)- or a heteroaryl-C(O)-. The aryl and heteroaryl portion of the aroyl or heteroaroyl is optionally substituted as defined elsewhere herein. For example, aroyl includes benzoyl.

[0074] As used herein, an “alkoxy” group refers to an alkyl-O- group where alkyl has been defined elsewhere herein.

[0075] As used herein, a “carbamoyl” group refers to a group having the formula -O-CO-NRXRYor -NRX-CO-O-RZ, wherein RXand RYhave been elsewhere herein and RZcan be alkyl, heteroalkyl, aryl, heteroaryl, etc.

[0076] As used herein, a “carboxy” group refers to -COOH, when used as a terminal group; or -OC(O)-, or -C(O)O- when used as an internal group.

[0077] As used herein, an “ester” refers to –COORXwhen used as a terminal group; or -COORX– when used as an internal group, wherein RXhas been defined elsewhere herein. As used herein, an “alkoxycarbonyl,” which is encompassed by the term ester, used alone or in connection with another group refers to a group such as alkyl-O-C(O)- (i.e., a carbonate ester).

[0078] As used herein, a “formate” refers to -OC(O)H.

[0079] As used herein, an “acetate” refers to -OC(O)RX, wherein RXhas been defined elsewhere herein. In one embodiment, acetate is -OC(O)Me.

[0080] As used herein, a “mercapto” or “sulfhydryl” group refers to -SH. - 20 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0081] As used herein, a “sulfo” group refers to -SO3H, or -SO3RXwhen used terminally or -S(O)3- when used internally. In one embodiment, -SO3H is a sulfonic acid. In one embodiment, RXSO3- is a sulfonate.

[0082] As used herein, a “sulfamide” group refers to the formula -NRX-S(O)2-NRYRZwhen used terminally and -NRX-S(O)2-NRY- when used internally, wherein RX, RY, and RZhave been defined elsewhere herein.

[0083] As used herein, a “sulfamoyl” group refers to the formula -S(O)2-NRYRZwherein RY, and RZhave been defined elsewhere herein. In one embodiment, -O-S(O)2-NRYRZis a sulfamate.

[0084] As used herein, a “sulfonamide” group refers to the formula RZ-S(O)2-NRXRYor -NRX-S(O)2-RZwhen used terminally; or -S(O)2-NRX-, or -NRX-S(O)2- when used internally, wherein RX, RY, and RZare defined elsewhere herein.

[0085] As used herein a “sulfide” group refers to -S-RXwhen used terminally and -S- when used internally, wherein RXhas been defined elsewhere herein. Examples of sulfanyls include aliphatic-S-, cycloalkyl-S-, aryl-S-, or the like.

[0086] As used herein a “sulfinyl” group refers to -S(O)-RXwhen used terminally and -S(O)- when used internally, wherein RXhas been defined elsewhere herein. Examples of sulfinyl groups include aliphatic-S(O)-, aryl-S(O)-, cycloalkyl-S(O)-, heterocycloaliphatic- S(O)-, heteroaryl-S(O)-, and / or the like.

[0087] As used herein, a “sulfonyl” group refers to -S(O)2-RXwhen used terminally and -S(O)2- when used internally, wherein RXhas been defined elsewhere herein. Examples of sulfonyl groups include aliphatic-S(O)2-, aryl-S(O)2-, cycloaliphatic-S(O)2-, heterocycloaliphatic-S(O)2-, heteroaryl-S(O)2-, and / or the like.

[0088] As used herein, a “sulfinate” group refers to -O-S(O)-RX, or -S(O)-O-RX, when used terminally and -O-S(O)- or -S(O)-O- when used internally, where RXhas been defined elsewhere herein.

[0089] As used herein, an “alkoxyalkyl” refers to an alkyl group modified with an alkoxy group, such as alkyl-O-alkyl- or ethers, wherein alkyl has been defined elsewhere herein.

[0090] As used herein, the term “phospho” refers to phosphinates, phosphonates, phosphine oxides, phosphoramidates, phosphinic amides, and phosphonamidates. Examples of phosphinates, phosphonates, phosphine oxides, phosphoramidates, phosphinic amides, and - 21 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT phosphonamidates include -P(O)(RP)2, (RP)2P(O)ORP, and RP-PO(ORP)2, wherein RPis aliphatic, alkoxy, aryloxy, heteroaryloxy, aryl, heteroaryl, cycloalkyl, or amino.

[0091] As used herein, an “aminoalkyl” refers to the formula (RX)2N-alkyl- where RXhas been defined elsewhere herein.

[0092] As used herein, a “cyanoalkyl” refers to the formula (NC)-alkyl-.

[0093] As used herein, a “urea” group refers to the formula -NRX-C(O)-NRYRZand a “thiourea” refers to the formula -NRX-C(S)-NRYRZeach when used terminally and -NRX-C(O)-NRY- or -NRX-C(S)-NRY- each when used internally, wherein RX, RY, and RZhave been defined elsewhere herein.

[0094] As used herein, a “guanidine” group refers to the formula -N=C(N(RXRY))(N(RXRY)) or -NRX-C(=NRX)NRXRYwherein RXand RYhave been defined elsewhere herein.

[0095] As used herein, the term “amidino” group refers to the formula -C(NRX)NRXRYwherein RXand RYhave been defined elsewhere herein.

[0096] As used herein, the term “vicinal” generally refers to the placement of substituents on a group that includes two or more carbon atoms, wherein the substituents are attached to adjacent carbon atoms.

[0097] As used herein, the term “geminal” generally refers to the placement of substituents on the same carbon atom.

[0098]

[0099] “Optionally substituted,” unless otherwise specified, means that a group is unsubstituted or substituted by one or more (e.g., one, two, three, four, or five) of the substituents listed for that group, in which the substituents may be the same or different. In one embodiment, an optionally substituted group is unsubstituted. In one embodiment, an optionally substituted group has one substituent. In another embodiment, an optionally substituted group has two substituents. In another embodiment, an optionally substituted group has three substituents. In another embodiment, an optionally substituted group has four substituents. In some embodiments, an optionally substituted group has one to two, one to three, one to four, or one to five substituents. When multiple substituents are present, each substituent is independently chosen unless indicated otherwise. For example, each (C1-C4 alkyl) substituent on the group –N(C1-C4 alkyl)(C1-C4 alkyl) can be selected independently from the other, so as to generate groups such as –N(CH3)(CH2CH3), etc. - 22 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0100] “Substituted” as used herein, for example, when used to modify a specified group or radical, can also mean that one or more hydrogen atoms (H) of the specified group or radical are each, independently of one another, replaced with the same or different substituent groups as defined herein. In some embodiments, a group that is substituted has one, two, three, or four substituents, one, two, or three substituents, one or two substituents, or one substituent. Substituents can be attached to any chemically possible location on the specified group or radical, unless indicated otherwise. Thus, for example, in one embodiment, -C1-C8 alkyl-OH includes, for example, -CH2CH2OH and -CH(OH)-CH3, and -CH2C(OH)(CH3)2, and the like. By way of further example, in one embodiment, -C1-C6alkyl-OH includes, for example, -CH2CH2OH and -CH(OH)-CH3, and -CH2C(OH)(CH3)2, and the like. By way of further example, in one embodiment, -C1-C6 alkyl-CN includes, for example, -CH2CH2CN and -CH(CN)-CH3, and -CH2C(CN)(CH3)2, and the like. A ring substituent, such as a heterocycloalkyl, can be bound to another ring, such as a cycloalkyl, to form a spiro-bicyclic ring system, for example, both rings share one common atom. Non-limiting examples of spiro heterocycloalkyls include; ; ;; and . Spiro compounds depicted with overlapping rings indicate that the spirocyclic rings can bond at any vertex. For instance, in the spiro group, the two rings can bond at any of the three available vertex atoms in either ring.

[0101] Unless a specific isotope of an element is indicated in a formula, the disclosure includes all isotopologues of the compounds disclosed herein, such as, for example, deuterated derivatives of the compounds (where H can be 2H, i.e., deuterium (D)). Deuterated compounds may provide favorable changes in pharmacokinetic (PK or ADME) properties. Isotopologues can have isotopic replacements at any or at all locations in a chemcical structure, or can have atoms present in natural abundance at any or all locations in a structure. - 23 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0102] Hydrogen atoms can also be replaced with close bioisosteres, such as fluorine, provided that such replacements result in stable compounds.

[0103] This disclosure also includes any or all of the stereochemical forms, including any enantiomeric or diastereomeric forms of the compounds described herein, and cis- / trans- or E- / Z- isomers. Unless stereochemistry is explicitly indicated in a chemical structure or name, the structure or name is intended to embrace all possible stereoisomers of a compound depicted. In addition, where a specific stereochemical form is depicted, it is understood that all other stereochemical forms are also described and embraced by this disclosure, as well as the general non-stereospecific form and mixtures of the disclosed compounds in any ratio, including mixtures of two or more stereochemical forms of a disclosed compound in any ratio, such that racemic, non-racemic, enantioenriched, and scalemic mixtures of a compound are embraced. Compositions comprising a disclosed compound also are intended, such as a composition of substantially pure compound, including a specific stereochemical form thereof. Compositions comprising a mixture of disclosed compounds in any ratio also are embraced by this disclosure, including compositions comprising mixtures of two or more stereochemical forms of a disclosed compound in any ratio, such that racemic, non-racemic, enantioenriched, and scalemic mixtures of a compound are embraced by this disclosure. If stereochemistry is explicitly indicated for one portion or portions of a molecule, but not for another portion or portions of a molecule, the structure is intended to embrace all possible stereoisomers for the portion or portions where stereochemistry is not explicitly indicated. This disclosure also embraces any and all tautomeric forms of the compounds described herein.

[0104] This disclosure is intended to embrace all salts of the compounds described herein, as well as methods of using such salts of the compounds. In one embodiment, the salts of the compounds comprise pharmaceutically acceptable salts. Pharmaceutically acceptable salts are those salts that can be administered as drugs or pharmaceuticals to humans and / or animals and that, upon administration, retain at least some of the biological activity of the free compound (i.e., neutral compound or non-salt compound). The desired salt of a basic compound may be prepared by methods known to those of skill in the art by treating the compound with an acid. Examples of inorganic acids include, but are not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Examples of organic acids include, but are not limited to, formic acid, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, sulfonic acids, and salicylic acid. Salts of basic compounds with - 24 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT amino acids, such as aspartate salts and glutamate salts, also can be prepared. The desired salt of an acidic compound can be prepared by methods known to those of skill in the art by treating the compound with a base. Examples of inorganic salts of acid compounds include, but are not limited to, alkali metal and alkaline earth salts, such as sodium salts, potassium salts, magnesium salts, and calcium salts; ammonium salts; and aluminum salts. Examples of organic salts of acid compounds include, but are not limited to, procaine, dibenzylamine, N- ethylpiperidine, N,N'-dibenzylethylenediamine, and triethylamine salts. Salts of acidic compounds with amino acids, such as lysine salts, also can be prepared. For lists of pharmaceutically acceptable salts, see, for example, P. H. Stahl and C. G. Wermuth (eds.) “Handbook of Pharmaceutical Salts, Properties, Selection and Use” Wiley-VCH, 2011 (ISBN: 978-3-90639-051-2). Several pharmaceutically acceptable salts are also disclosed in Berge, J. Pharm. Sci.66:1 (1977).

[0105] Certain features disclosed herein, which are, for clarity, described in the context of separate embodiments, also may be provided in combination in a single embodiment. Conversely, various features disclosed herein, which are, for brevity, described in the context of a single embodiment, also may be provided separately or in any suitable subcombination. All combinations of the embodiments pertaining to the chemical groups represented by the variables are specifically embraced by this disclosure and are disclosed herein just as if each and every combination was individually and explicitly disclosed, to the extent that such combinations embrace compounds that are stable compounds (i.e., compounds that can be isolated, characterized, and tested for biological activity). In addition, all subcombinations of the chemical groups listed in the embodiments describing such variables also are specifically embraced by this disclosure and are disclosed herein just as if each and every such subcombination of chemical groups was individually and explicitly disclosed herein.

[0106] It is understood that aspects and embodiments described herein as “comprising” include “consisting of” and “consisting essentially of” embodiments.

[0107] As used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless otherwise indicated or clear from context. For example, “an” excipient includes one or more excipients.

[0108] Reference to “about” a value, encompasses from 90% to 110% of that value. For instance, about 50 billion cells refers to 45 to 55 billion cells, and includes 50 billion cells. For instance, a temperature of “about 100 degrees” refers to a temperature of about 90 degrees to about 110 degrees. - 25 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0109] The terms “baseline” or “baseline value” as used herein can refer to a measurement or characterization before administration of a therapeutic agent as disclosed herein (e.g., a composition comprising an Aurora kinase inhibitor as described herein) or at the beginning of administration of the therapeutic agent. The baseline value can be compared to a reference value in order to determine the increase or decrease of function (e.g., increasing activation, increasing proliferation, decreasing activation, or descreasing proliferation). The terms “reference” or “reference value” as used herein can refer to a measurement or characterization after administration of the therapeutic agent as disclosed herein (e.g., a composition comprising an Aurora kinase inhibitor as described herein). The reference value can be measured one or more times during an experimental time course, dosage regimen, or treatment cycle, or at the completion of the experimental time course, dosage regimen, or treatment cycle. A reference value can be an absolute value, a relative value, a value that has an upper and / or lower limit, a range of values, an average value, a median value, a mean value, or a value as compared to a baseline value. Similarly, a baseline value can be an absolute value, a relative value, a value that has an upper and / or lower limit, a range of values, an average value, a median value, a mean value, or a value as compared to a reference value. The reference value and / or baseline value can be obtained from one sample (e.g., one sample obtained from an individual), from two different samples (e.g., a sample obtained from two different individuals) or from a group of samples (e.g., samples obtained from a group of two, three, four, five, or more individuals).

[0110] As used herein the term “biosimilar” refers to a biological product that is similar to but without clinically meaningful differences in safety and effectiveness from a Federal Drug Administration (FDA)-approved reference product. For instance, there may be differences between a biosimilar product and a reference product in clinically inactive components (e.g., differences in excipients of the formulations, minor differences in glycosylation, etc.). Clinically meaningful characteristics can be assessed through pharmacokinetic and pharmacodynamic studies. In some embodiments, the biosimilar product is an interchangeable product as determined by the FDA. In some embodiments, the cancer vaccine is a biosimilar of an FDA-approved product.

[0111] As used herein, “enantiomeric excess (ee)” refers to a dimensionless mol ratio describing the purity of chiral substances that contain, for example, a single stereogenic center. For instance, an enantiomeric excess of zero would indicate a racemic (e.g., 50:50 mixture of enantiomers, or no excess of one enantiomer over the other). By way of further example, an enantiomeric excess of ninety-nine would indicate a nearly stereopure enantiomeric compound - 26 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT (i.e., large excess of one enantiomer over the other). The percentage enantiomeric excess, % ee = ([(R)-compound]-[(S)-compound]) / ([(R)-compound]+[(S)-compound]) x 100, where the (R)-compound > (S)-compound; or % ee = ([(S)-compound]-[(R)-compound]) / ([(S)- compound]+[(R)-compound]) x 100, where the (S)-compound > (R)-compound. Moreover, as used herein, “diastereomeric excess (de)” refers to a dimensionless mol ratio describing the purity of chiral substances that contain more than one stereogenic center. For example, a diastereomeric excess of zero would indicate an equimolar mixture of diastereoisomers. By way of further example, diastereomeric excess of ninety-nine would indicate a nearly stereopure diastereomeric compound (i.e., large excess of one diastereomer over the other). Diastereomeric excess may be calculated via a similar method to ee. As would be appreciated by a person of skill, de is usually reported as percent de (% de). % de may be calculated in a similar manner to % ee.

[0112] In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de greater than zero. For example, in certain embodments, the compounds or inhibitors described herein have an ee, de, % ee, or % de of ten. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de of twenty-five. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de of fifty. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de of seventy-five. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de of ninety-nine.

[0113] In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de range from ninety to one hundred. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de range from ninety-five to one hundred. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de range from ninety-seven to one hundred. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de range from ninety-eight to one hundred. In certain embodiments, the compounds or inhibitors described herein have an ee, de, % ee, or % de range from ninety-nine to one hundred.

[0114] In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is four. In one embodiment of a compound or inhibitor described herein, the - 27 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT ee, de, % ee, or % de is five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ten. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eleven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twelve. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirteen. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fourteen. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifteen. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixteen. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventeen. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighteen. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is nineteen. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty- three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-four. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is twenty-nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty-one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty- two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty-three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty-four. In one embodiment of a compound or inhibitor described herein, the - 28 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT ee, de, % ee, or % de is thirty-five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty-six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty-seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty-eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is thirty-nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty- one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty-two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty-three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty-four. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty-five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty-six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty-seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty-eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is forty-nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty- one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-four. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is fifty-nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty- one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty-two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty-three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty-four. In one embodiment of a compound or inhibitor described herein, - 29 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT the ee, de, % ee, or % de is sixty-five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty-six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty-seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty-eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is sixty-nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-four. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy- eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is seventy-nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty-one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty-two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty-three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty-four. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty-five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty- six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty-seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty-eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is eighty-nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety-one. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety-two. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety- three. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % - 30 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT de is ninety-four. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety-five. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety-six. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety-seven. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety-eight. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is ninety-nine. In one embodiment of a compound or inhibitor described herein, the ee, de, % ee, or % de is one hundred. In certain embodiments, compounds or inhibitors described within Table 1 herein have an ee, de, % ee, or % de as described within this paragraph.

[0115] Designation of an amino acid or amino acid residue without specifying its stereochemistry is intended to encompass the L- form of the amino acid, the D- form of the amino acid, or a racemic mixture thereof.

[0116] As used herein, the term “target protein” or “target polypeptide” refers to a protein or polypeptide and fragments thereof that are targets for binding by a small molecule compound (PTM) as described herein and is subject to further degradation by a ubiquitin ligase targeting moiety (UTM) as described herein. Such small molecule target protein binding moieties (PTMs) also include pharmaceutically acceptable salts, enantiomers, solvates, and polymorphs of these compositions, as well as other small molecules that may target a protein of interest. The small molecule binding moieties (PTMs) are linked to UTM groups via linker L groups.

[0117] Target proteins which may be bound to the protein target moiety and degraded by the ligase to which the ubiquitin ligase binding moiety is bound include structural proteins, receptors, enzymes, cell surface proteins, aromatases, helicases, kinases, oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases, enzyme regulators, signal transducers, behavioral proteins, cell adhesion proteins, proteins involved in cell death, protein transporters, nuclear transports, ion transporters, channel transporters, carriers, permeases, secretases, electron transporters, chaperones, nucleic acid binders, transcription regulators, and translation regulators. Proteins of interest can include proteins from eurkaryotes and prokaryotes, including microbes, viruses, fungi, and parasites, including humans, microbes, viruses, fungi, and parasites, among numerous others, as targets for drug therapy, other animals, including domesticated animals, microbials for the determination of targets for antibiotics and other antimicrobials and plants, and even viruses, among numerous others.

[0118] More specifically, a number of drug targets for human therapeutics represent protein targets to which protein target moiety may be bound and incorporated into compounds - 31 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT according to this disclosure. These include proteins which may be used to restore function in numerous polygenic diseases, including for example BRD4, ERRα, AR, RIPK2, B7.1, and B7, TINFRlm, TNFR2, NADPH oxidase, BclIBax, and other partners in the apotosis pathway, C5a receptor, HMG-CoA reductase, PDE V phosphodiesterase type, PDE IV phosphodiesterase type 4, PDE I, PDEII, PDEIII, squalene cyclase inhibitor, CXCR1, CXCR2, nitric oxide (NO) synthase, cyclo-oxygenase 1, cyclo-oxygenase 2, 5HT receptors, dopamine receptors, G Proteins (i.e., Gq), histamine receptors, 5-lipoxygenase, tryptase serine protease, thymidylate synthase, purine nucleoside phosphorylase, GAPDH trypanosomal, glycogen phosphorylase, Carbonic anhydrase, chemokine receptors, JAW STAT, RXR and similar, HIV 1 protease, HIV 1 integrase, influenza, neuramimidase, hepatitis B reverse transcriptase, sodium channel, multi drug resistance (MDR), protein P-glycoprotein (and MIRP), tyrosine kinases, CD23, CD124, tyrosine kinase p56 lck, CD4, CD5, IL-2 receptor, IL-1 receptor, TNF-alphaR, ICAM1, Cat+ channels, VCAM, VLA-4 integrin, selectins, CD40 / CD40L, newokinins and receptors, inosine monophosphate dehydrogenase, p38 MAP Kinase, RaslRaflMEWERK pathway, interleukin-1 converting enzyme, caspase, HCV, NS3 protease, HCV NS3 RNA helicase, glycinamide ribonucleotide formyl transferase, rhinovirus 3C protease, herpes simplex virus-1 (HSV-I), protease, cytomegalovirus (CMV) protease, poly (ADP-ribose) polymerase, cyclin dependent kinases, vascular endothelial growth factor, oxytocin receptor, microsomal transfer protein inhibitor, bile acid transport inhibitor, 5 alpha reductase inhibitors, angiotensin 11, glycine receptor, noradrenaline reuptake receptor, endothelin receptors, neuropeptide Y and receptor, estrogen receptors, androgen receptors, adenosine receptors, adenosine kinase and AMP deaminase, purinergic receptors (P2Y1, P2Y2, P2Y4, P2Y6, P2X1-7), farnesyltransferases, geranylgeranyl transferase, TrkA a receptor for NGF, beta-amyloid, tyrosine kinase Flk- IIKDR, vitronectin receptor, integrin receptor, Her-21 neu, telomerase inhibition, cytosolic phospholipaseA2 and EGF receptor tyrosine kinase. Additional protein targets include, for example, ecdysone 20-monooxygenase, ion channel of the GABA gated chloride channel, acetylcholinesterase, voltage-sensitive sodium channel protein, calcium release channel, and chloride channels. Still further, target proteins include Acetyl-CoA carboxylase, adenylosuccinate synthetase, protoporphyrinogen oxidase, and enolpyruvylshikimate- phosphate synthase.

[0119] As used herein, the term “mediators of abnormal cellular proliferation” refers to a tumor or cancer, wherein a target protein is an oncogenic protein or a signaling mediator of an - 32 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT abnormal cellular proliferative pathway and degradation of the target protein decreases abnormal cell growth.

[0120] As used herein, the term “residue” refers to the chemical moiety within a compound that remains after a chemical reaction. For example, the term “amino acid residue” or “N-alkyl amino acid residue” refers to the product of an amide coupling or peptide coupling of an amino acid or a N-alkyl amino acid to a suitable coupling partner; wherein, for example, a water molecule is expelled after the amide or peptide coupling of the amino acid or the N-alkylamino acid, resulting in the product having the amino acid residue or N-alkyl amino acid residue incorporated therein. The term “amino acid” refers to naturally occurring and synthetic ^, ^, ^, or ^ amino acids, and includes, but is not limited to, amino acids found in proteins, namely, glycine, homoglycine or ^-homoglycine or ^-alanine, alanine, valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, proline, serine, threonine, cysteine, tyrosine, asparagine, glutamine, aspartate, glutamate, lysine, arginine, and histidine. In certain embodiments, the amino acid is in the L-configuration. Alternatively, the amino acid can be a derivative of alanyl, valinyl, leucinyl, isoleucinyl, prolinyl, phenylalaninyl, tryptophanyl, methioninyl, glycinyl, serinyl, threoninyl, cysteinyl, tyrosinyl, asparaginyl, glutaminyl, aspartoyl, glutaroyl, lysinyl, argininyl, histidinyl, ^-alanyl, ^-valinyl, ^-leucinyl, ^- isoleuccinyl, ^-prolinyl, ^-phenylalaninyl, ^-tryptophanyl, ^-methioninyl, ^-glycinyl, ^- serinyl, ^-threoninyl, ^-cysteinyl, ^-tyrosinyl, ^-asparaginyl, ^-glutaminyl, ^-aspartoyl, ^- glutaroyl, ^-lysinyl, ^-argininyl or ^-histidinyl. The term “amino acid derivative” refers to a group derivable from a naturally or non-naturally occurring amino acid, as described and exemplified herein. Amino acid derivatives are apparent to those of skill in the art and include, but are not limited to, ester, amino alcohol, amino aldehyde, amino lactone, and N-methyl derivatives of naturally and non-naturally occurring amino acids. In certain embodiments, an, , , ,, wherein Scis a side chain of a naturally occurring or non- naturally occurring amino acid or a bond (e.g., hydrogen, as in glycine; -CH2OH as in serine; -CH2SH as in cysteine; -CH2CH2CH2CH2NH2as in lysine; -CH2CH2COOH as in glutamic - 33 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT acid; -CH2CH2C(O)NH2 as in glutamine; or -CH2C6H5OH as in tyrosine; and the like); andrepresents the bonding to another chemical entity. In certain embodiments, Scis selected from the group consisting of hydrogen, alkyl, heteroalkyl, arylalkyl, and heteroarylalkyl.

[0121] Certain groups, moieties, substituents, and atoms are depicted with a wiggly line that intersects a bond or bonds to indicate the atom through which the groups, moieties, substituents, atoms are bonded. For example, a phenyl group that is substituted with a propyl group depicted as: or orhas the following structure: . As used herein, illustrations showing substituents bonded to a cyclic group (e.g., aromatic, heteroaromatic, fused ring, and saturated or unsaturated cycloalkyl or heterocycloalkyl) through a bond between ring atoms are meant to indicate, unless specified otherwise, that the cyclic group may be substituted with that substituent at any ring position in the cyclic group or on any ring in the fused ring group, according to techniques set forth herein or which are known in the field to which the instant disclosure pertains. For example, the grouporwherein subscript q is an integer from zero to four and in which the positions of substituent R1are described generically (i.e., not directly attached to any vertex of the bond line structure, i.e., specific ring carbon atom), includes the following non-limiting examples of groups in which the substituent R1is bonded to a specific ring carbon atom:,- 34 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0122] As used herein, the term “immunoglobulin” refers to a class of structurally related proteins generally comprising two pairs of polypeptide chains: one pair of light (L) chains and one pair of heavy (H) chains. In an “intact immunoglobulin,” all four of these chains are interconnected by disulfide bonds. The structure of immunoglobulins has been well characterized. See, e.g., Paul, Fundamental Immunology 7th ed., Ch. 5 (2013) Lippincott Williams & Wilkins, Philadelphia, PA. Briefly, each heavy chain typically comprises a heavy chain variable region (VH or VH) and a heavy chain constant region (CH or CH). The heavy chain constant region typically comprises three domains, abbreviated CH1 (or CH1), CH2 (or CH2), and CH3 (or CH3). Each light chain typically comprises a light chain variable region (VLor VL) and a light chain constant region. The light chain constant region typically comprises one domain, abbreviated CL or CL.

[0123] The term “antibody” is used herein in its broadest sense. An antibody includes intact antibodies (e.g., intact immunoglobulins) and antibody fragments (e.g., antigen binding fragments of antibodies). Antibodies comprise at least one antigen-binding domain. One example of an antigen-binding domain is an antigen binding domain formed by a VH-VLdimer.

[0124] The VHand VLregions may be further subdivided into regions of hypervariability (viz., “hypervariable regions” (HVRs); also called “complementarity determining regions” (CDRs)) interspersed with regions that are more conserved. The more conserved regions are called framework regions (FRs). Each VHand VLgenerally comprises three CDRs and four FRs arranged in the following order (from N-terminus to C-terminus): FR1 - CDR1 - FR2 - CDR2 - FR3 - CDR3 - FR4. The CDRs are involved in antigen binding, and influence antigen specificity and binding affinity of the antibody. See Kabat et al., Sequences of Proteins of - 35 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT Immunological Interest 5th ed. (1991) Public Health Service, National Institutes of Health, Bethesda, MD, incorporated by reference herein in its entirety.

[0125] The light chain from any vertebrate species can be assigned to one of two types, called kappa and lambda, based on the sequence of the constant domain.

[0126] The heavy chain from any vertebrate species can be assigned to one of five different classes (or isotypes): IgA, IgD, IgE, IgG, and IgM. These classes are also designated α, δ, ε, γ, and µ, respectively. The IgG and IgA classes are further divided into subclasses based on differences in sequence and function. Humans express the following subclasses: IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2.

[0127] The amino acid sequence boundaries of a CDR can be determined by one of skill in the art using any of a number of known numbering schemes, including those described by Kabat et al., supra (viz., the “Kabat” numbering scheme); Al-Lazikani et al., 1997, J. Mol. Biol., 273:927-948 (viz., the “Chothia” numbering scheme); MacCallum et al., 1996, J. Mol. Biol. 262:732-745 (viz., the “Contact” numbering scheme); Lefranc et al., Dev. Comp. Immunol., 2003, 27:55-77 (viz., the “IMGT” numbering scheme); and Honegge and Plückthun, J. Mol. Biol., 2001, 309:657-70 (viz., the “AHo” numbering scheme), each of which is incorporated herein by reference in its entirety.

[0128] Table A provides the positions of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, and CDR-H3 as identified by the Kabat and Chothia schemes. For CDR-H1, residue numbering is provided using both the Kabat and Chothia numbering schemes.

[0129] Table A. Residues in CDRs according to Kabat and Chothia numbering schemes.

[0130] * The C-terminus of CDR-H1, when numbered using the Kabat numbering convention, varies between H32 and H34, depending on the length of the CDR.

[0131] Unless otherwise specified, the numbering scheme used for identification of a particular CDR herein is the Kabat / Chothia numbering scheme. Where the residues encompassed by these two numbering schemes diverge (e.g., CDR-H1 and / or CDR-H2), the - 36 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT numbering scheme is specified as either Kabat or Chothia. For convenience, CDR-H3 is sometimes referred to herein as either Kabat or Chothia. However, this is not intended to imply differences in sequence where they do not exist, and one of skill in the art can readily confirm whether the sequences are the same or different by examining the sequences.

[0132] CDRs may be assigned, for example, using antibody numbering software, such as Abnum, available at www.bioinf.org.uk / abs / abnum / , and described in Abhinandan and Martin, Immunology, 2008, 45:3832-3839, incorporated herein by reference in its entirety.

[0133] The “EU numbering scheme” is generally used herein when referring to a residue in an antibody heavy chain constant region (e.g., as reported in Kabat et al., supra). Unless stated otherwise, the EU numbering scheme is used to refer to residues in antibody heavy chain constant regions described herein.

[0134] An “antibody fragment” as used herein comprises a portion of an intact antibody, such as the antigen binding or variable region of an intact antibody. Antibody fragments include, for example, Fv fragments, Fab fragments, F(ab’)2 fragments, Fab’ fragments, scFv (sFv) fragments, scFv-Fc fragments, diabodies, triabodies, tertrabodies, minibodies, nanobodies, and the like.

[0135] “Fv” fragments as used herein comprise a non-covalently-linked dimer of one heavy chain variable domain and one light chain variable domain.

[0136] “Fab” fragments as used herein comprise, in addition to the heavy and light chain variable domains, the constant domain of the light chain and the first constant domain (CH1) of the heavy chain. Fab fragments may be generated, for example, by recombinant methods or by papain digestion of a full-length antibody.

[0137] “F(ab′)2” fragments as used herein contain two Fab′ fragments joined, near the hinge region, by disulfide bonds. F(ab′)2 fragments may be generated, for example, by recombinant methods or by pepsin digestion of an intact antibody. The F(ab′) fragments can be dissociated, for example, by treatment with β-mercaptoethanol.

[0138] “Single-chain Fv” or “sFv” or “scFv” antibody fragments as used herein comprise a VH domain and a VL domain in a single polypeptide chain. The VH and VL are generally linked by a peptide linker. See Plückthun A. (1994). In some embodiments, the linker is GGGGSGGGGSGGGGS (SEQ ID NO.:1). In some embodiments, the linker is AAGSDQEPKSS (SEQ ID NO.:2). Antibodies from Escherichia coli. In Rosenberg M. & Moore G.P. (Eds.), The Pharmacology of Monoclonal Antibodies vol. 113 (pp. 269-315). Springer-Verlag, New York, incorporated herein by reference in its entirety. - 37 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0139] “scFv-Fc” fragments as used herein comprise an scFv attached to an Fc domain. For example, an Fc domain may be attached to the C-terminus of the scFv. The Fc domain may follow the VH or VL, depending on the orientation of the variable domains in the scFv (i.e., VH-VL or VL-VH). Any suitable Fc domain known in the art or described herein may be used. In some cases, the Fc domain comprises an IgG1 Fc domain. In some embodiments, the IgG1 Fc domain comprises SEQ ID NO.:3, or a portion thereof. SEQ ID NO.:3 provides the sequence of CH1, CH2, and CH3 of the human IgG1 constant region: AAGSDQEPKSSDKTHTCPPCSAPELLGGSSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP EVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK.

[0140] As used herein, the term “monoclonal antibody” refers to an antibody from a population of substantially homogeneous antibodies. A population of substantially homogeneous antibodies comprises antibodies that are substantially similar and that bind the same epitope(s), except for variants that may normally arise during production of the monoclonal antibody. Such variants are generally present in only minor amounts. A monoclonal antibody is typically obtained by a process that includes the selection of a single antibody from a plurality of antibodies. For example, the selection process can be the selection of a unique clone from a plurality of clones, such as a pool of hybridoma clones, phage clones, yeast clones, bacterial clones, or other recombinant DNA clones. The selected antibody can be further altered, for example, to improve affinity for the target (“affinity maturation”), to humanize the antibody, to improve its production in cell culture, and / or to reduce its immunogenicity in a subject.

[0141] As used herein, term “chimeric antibody” refers to an antibody in which a portion of the heavy and / or light chain is derived from a particular source or species, while the remainder of the heavy and / or light chain is derived from a different source or species.

[0142] As used herein, “humanized” forms of non-human antibodies are chimeric antibodies that contain minimal sequences derived from the non-human antibody. A humanized antibody is generally a human immunoglobulin (recipient antibody) in which residues from one or more CDRs are replaced by residues from one or more CDRs of a non-human antibody (donor antibody). The donor antibody can be any suitable non-human antibody, such as a mouse, rat, rabbit, chicken, or non-human primate antibody having a desired specificity, affinity, or biological effect. In some instances, selected framework region residues of the - 38 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT recipient antibody are replaced by the corresponding framework region residues from the donor antibody. Humanized antibodies may also comprise residues that are not found in either the recipient antibody or the donor antibody. Such modifications may be made to further refine antibody function. For further details, see Jones et al., Nature, 1986, 321:522-525; Riechmann et al., Nature, 1988, 332:323-329; and Presta, Curr. Op. Struct. Biol., 1992, 2:593-596, each of which is incorporated herein by reference in its entirety.

[0143] As used herein, a “human antibody” is one which possesses an amino acid sequence corresponding to that of an antibody produced by a human or a human cell, or derived from a non-human source that utilizes a human antibody repertoire or human antibody-encoding sequences (e.g., obtained from human sources or designed de novo). Human antibodies specifically exclude humanized antibodies.

[0144] As used herein, an “isolated antibody” is one that has been separated and / or recovered from a component of its natural environment. Components of the natural environment may include enzymes, hormones, and other proteinaceous or nonproteinaceous materials. In some embodiments, an isolated antibody is purified to a degree sufficient to obtain at least fifteen residues of N-terminal or internal amino acid sequence, for example by use of a spinning cup sequenator. In some embodiments, an isolated antibody is purified to homogeneity by gel electrophoresis (e.g., SDS-PAGE) under reducing or nonreducing conditions, with detection by Coomassie blue or silver stain. An isolated antibody includes an antibody in situ within recombinant cells, since at least one component of the antibody’s natural environment is not present. In some aspects, an isolated antibody is prepared by at least one purification step.

[0145] In some embodiments, an isolated antibody is purified to at least 80%, 85%, 90%, 95%, or 99% by weight. In some embodiments, an isolated antibody is purified to at least 80%, 85%, 90%, 95%, or 99% by volume. In some embodiments, an isolated antibody is provided as a solution comprising at least 85%, 90%, 95%, 98%, or 99% to 100% by weight. In some embodiments, an isolated antibody is provided as a solution comprising at least 85%, 90%, 95%, 98%, or 99% to 100% by volume.

[0146] As used herein, “affinity” refers to the strength of the sum total of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless indicated otherwise, as used herein, “binding affinity” refers to intrinsic binding affinity, which reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen). The affinity of a molecule X for its partner Y can be represented - 39 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT by the dissociation constant (KD). Affinity can be measured by common methods known in the art, including those described herein. Affinity can be determined, for example, using surface plasmon resonance (SPR) technology, such as a Biacore®instrument. In some embodiments, the affinity is determined at 25 °C.

[0147] With regard to the binding of an antibody to a target molecule, the terms “specific binding,” “specifically binds to,” “specific for,” “selectively binds,” and “selective for” a particular antigen (e.g., a polypeptide target) or an epitope on a particular antigen mean binding that is measurably different from a non-specific or non-selective interaction. Specific binding can be measured, for example, by determining binding of a molecule compared to binding of a control molecule. Specific binding can also be determined by competition with a control molecule that mimics the antibody binding site on the target. In that case, specific binding is indicated if the binding of the antibody to the target is competitively inhibited by the control molecule.

[0148] As used herein, the term “amino acid” refers to the twenty common naturally occurring amino acids. Naturally occurring amino acids include alanine (Ala; A), arginine (Arg; R), asparagine (Asn; N), aspartic acid (Asp; D), cysteine (Cys; C); glutamic acid (Glu; E), glutamine (Gln; Q), Glycine (Gly; G); histidine (His; H), isoleucine (Ile; I), leucine (Leu; L), lysine (Lys; K), methionine (Met; M), phenylalanine (Phe; F), proline (Pro; P), serine (Ser; S), threonine (Thr; T), tryptophan (Trp; W), tyrosine (Tyr; Y), and valine (Val; V), and the less common pyrrolysine and selenocysteine. Natural amino acids also include citrulline. Naturally encoded amino acids include post-translational variants of the twenty-two naturally occurring amino acids such as prenylated amino acids, isoprenylated amino acids, myristoylated amino acids, palmitoylated amino acids, N-linked glycosylated amino acids, O-linked glycosylated amino acids, phosphorylated amino acids, and acylated amino acids. The term “amino acid” also includes “non-natural amino acids” and “modified amino acids.” The terms “non-natural amino acids” and “modified amino acids” are used herein interchangeably.

[0149] As used herein, the term “conjugate” or “antibody conjugate” refers to an antibody linked to one or more payload moieties. The antibody can be any antibody described herein. The payload can be any payload described herein. The antibody can be directly linked to the payload via a covalent bond, or the antibody can be linked to the payload indirectly via a linker. Typically, the linker is covalently bonded to the antibody and also covalently bonded to the payload. The term “antibody drug conjugate” or “ADC” refers to a conjugate wherein at least one payload is a therapeutic moiety such as a drug. The term “drug-antibody conjugate” or - 40 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT “degrader-antibody conjugate” or “DAC” refers to a conjugate wherein at least one payload is a therapeutic moiety such as a drug.

[0150] As used herein, term “epitope” means a portion of an antigen capable of specific binding to an antibody. Epitopes frequently consist of surface-accessible amino acid residues and / or sugar side chains and may have specific three-dimensional structural characteristics, as well as specific charge characteristics. Conformational and non-conformational epitopes are distinguished in that the binding to the former but not the latter is lost in the presence of denaturing solvents. An epitope may comprise amino acid residues that are directly involved in the binding, and other amino acid residues, which are not directly involved in the binding. The epitope to which an antibody binds can be determined using known techniques for epitope determination.

[0151] Percent “identity” between a polypeptide sequence and a reference sequence, is defined as the percentage of amino acid residues in the polypeptide sequence that are identical to the amino acid residues in the reference sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, CLUSTAL OMEGA, or MUSCLE software. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared.

[0152] As used herein, a “conservative substitution” or a “conservative amino acid substitution” refers to the substitution of an amino acid with a chemically or functionally similar amino acid. Conservative substitution tables providing similar amino acids are well known in the art. Polypeptide sequences having such substitutions are known as “conservatively modified variants.” Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles. By way of example, the groups of amino acids provided in Tables B-D are, in some embodiments, considered conservative substitutions for one another. Table B. Selected groups of amino acids that are considered conservative substitutions for one another, in certain embodiments.- 41 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCTTable C. Additional selected groups of amino acids that are considered conservative substitutions for one another, in certain embodiments.Table D. Further selected groups of amino acids that are considered conservative substitutions for one another, in certain embodiments.

[0153] Additional conservative substitutions may be found, for example, in Creighton, Proteins: Structures and Molecular Properties 2nd ed. (1993) W. H. Freeman & Co., New York, NY. An antibody generated by making one or more conservative substitutions of amino acid residues in a parent antibody is referred to as a “conservatively modified variant.”

[0154] As used herein, the term “linker” refers to a molecular moiety that is capable of forming at least two covalent bonds. Typically, a linker is capable of forming at least one covalent bond to an antibody and at least another covalent bond to a payload. In certain embodiments, a linker can form more than one covalent bond to an antibody. In certain - 42 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT embodiments, a linker can form more than one covalent bond to a payload or can form covalent bonds to more than one payload. After a linker forms a bond to an antibody, or a payload, or both, the remaining structure, meaning, the residue of the linker after one or more covalent bonds are formed, may still be referred to as a “linker” herein. The term “linker precursor” refers to a linker having one or more reactive groups (RGs) capable of forming a covalent bond with an antibody or payload, or both. In some embodiments, the linker is a cleavable linker. For example, a cleavable linker can be one that is released by a bio-labile function, which may or may not be engineered. In some embodiments, the linker is a non-cleavable linker. For example, a non-cleavable linker can be one that is released upon degradation of the antibody.

[0155] As used herein, the term “’7+3’ chemotherapy or regimen” refers to a seven-day continuous infusion of cytarabine and a three-day infusion of an anthracycline drug, for example, daunorubicin or idarubicin.

[0156] As used herein, the term “LY3295668” or “LY5668” refers to.

[0157] As used herein, the terms “refractory,” “resistant,” and / or “resistant-refractory” refer to a disease or condition that does not respond to treatment. For example, a taxane- refractory cancer is a cancer that does not respond to taxane treatment; a platinum-refractory cancer is a cancer that does not respond to platinum treatment; and a checkpoint-refractory cancer is a cancer that does not respond to checkpoint treatment. Taxane-resistant, platinum- resistant, and checkpoint-resistant are synonymous to or interchangeable with taxane- refractory, platinum-refractory, and checkpoint-refractory, respectively. By way of further example, refractory, resistant, or resistant-refractory cancers can be refractory or resistant at the beginning of treatment, or can become refractory or resistant during treatment. Compounds

[0158] The compounds or degraders described herein offer therapeutic potential to treat both Aurora and N-Myc-driven malignancies, including but not limited to neuroblastoma (particularly cases with MYCN amplification), SCLC (particularly MYC family–amplified - 43 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT subsets), medulloblastoma (particularly Group 2-3 tumors with MYC or MYCN overexpression), pediatric gliomas and retinoblastomas (particularly those dependent on MYCN overexpression), triple-negative breast cancer, high-grade serous ovarian cancer, colorectal cancer, retinoblastoma, prostate cancer with neuroendocrine features (NEPC subtype), Wilms tumor, and Ewing sarcoma. The compounds or degraders described herein provide effective therapeutic potential that in addition to overcoming the issues associated with inhibiting Aurora A as a target in Aurora A dependent cancers, cure the limitations of enzymatic inhibition, and enable targeting of an otherwise undruggable driver, MYCN.

[0159] Together, these findings, and the data provided herein underscore the value of targeted degradation of Aurora A, which eliminates both catalytic and non-catalytic functions involved in mitotic fidelity and oncogenic stabilization.

[0160] In general, the compounds disclosed herein can be in racemic form. In general, the compounds disclosed herein can be in nonraemic form. In general, the compounds disclosed herein can have an enantiomeric excess as described elsewhere herein. In general, the compounds disclosed herein can have a diastereomeric excess as described elsewhere herein. In certain embodiments, the compounds disclosed herein are shown in Table 1.

[0161] In certain embodiments, provided herein are compounds represented by Formula Afurther wherein R1is, independently, hydrogen, bromo, chloro, fluoro, or iodo; X1is bromo, chloro, fluoro, or iodo; X2is oxygen; X3is alkylene; -C(O)-;; ; or unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, haloalkyl, halogen, -C(O)-, or -SO2-; and X4is carbon. In certain embodiments, each R1is hydrogen. In certain embodiments, one R1is hydrogen and the other R1is bromo. In certain embodiments, one R1is hydrogen and the other R1is chloro. In certain embodiments, one R1is hydrogen and the other R1is fluoro. In certain embodiments, one R1is hydrogen and the other R1is iodo. In certain embodiments, each R1is bromo. In certain embodiments, each R1is chloro. In certain embodiments, each R1is fluoro. In certain embodiments, each R1is iodo. In certain - 44 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT embodiments, one R1is bromo and the other R1is chloro. In certain embodiments, one R1is bromo and the other R1is fluoro. In certain embodiments, one R1is bromo and the other R1is iodo. In certain embodiments, one R1is chloro and the other R1is fluoro. In certain embodiments, one R1is chloro and the other R1is iodo. In certain embodiments, one R1is fluoro and the other R1is iodo. In certain embodiments, X1is bromo. In certain embodiments, X1is chloro. In certain embodiments, X1is fluoro. In certain embodiments, X1is iodo. In certain embodiments, X3is alkylene. In certain embodiments, X3is -C(O)-. In certain embodiments, X3is. In certain embodiments, X3. certain embodiments, X3is an unsubstituted heterocycloalkylene. In certain embodiments, X3is a substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, haloalkyl, halogen, -C(O)-, or -SO2-. Other combinations or perturbations between R1, X1, and X3described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0162] In certain embodiments, provided herein are compounds represented by Formula Afurther wherein R1is hydrogen, bromo, chloro, fluoro, or iodo; X1is bromo, chloro, fluoro, or iodo; X2is oxygen; X3is alkylene; -C(O)-;;unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, haloalkyl, halogen, -C(O)-, or -SO2-; and X4is nitrogen wherein the R1bound to X4is absent. In certain embodiments, R1is hydrogen. In certain embodiments, R1is bromo. In certain embodiments, R1is chloro. In certain embodiments, R1is fluoro. In certain embodiments, R1is iodo. In certain embodiments, X1is bromo. In certain embodiments, X1is chloro. In certain embodiments, X1is fluoro. In certain embodiments, X1is iodo. In certain embodiments, X3is alkylene. In certain - 45 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT embodiments, X3is -C(O)-. In certain embodiments, X3. certain embodiments, X3is . In certain embodiments, X3is an unsubstituted heterocycloalkylene. In certain embodiments, X3is a substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, haloalkyl, halogen, -C(O)-, or -SO2-. Other combinations or perturbations between R1, X1, and X3described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0163] In certain embodiments, provided herein are compounds represented by Formula Bfurther wherein R1is, independently, hydrogen, bromo, chloro, fluoro, or iodo; X1is bromo, chloro, fluoro, or iodo; X2is oxygen; X3is alkylene; -C(O)-;; ; or unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, haloalkyl, halogen, -C(O)-, or -SO2-; and X4is carbon. In certain embodiments, each R1is hydrogen. In certain embodiments, one R1is hydrogen and the other R1is bromo. In certain embodiments, one R1is hydrogen and the other R1is chloro. In certain embodiments, one R1is hydrogen and the other R1is fluoro. In certain embodiments, one R1is hydrogen and the other R1is iodo. In certain embodiments, each R1is bromo. In certain embodiments, each R1is chloro. In certain embodiments, each R1is fluoro. In certain embodiments, each R1is iodo. In certain embodiments, one R1is bromo and the other R1is chloro. In certain embodiments, one R1is bromo and the other R1is fluoro. In certain embodiments, one R1is bromo and the other R1is iodo. In certain embodiments, one R1is chloro and the other R1is fluoro. In certain embodiments, one R1is chloro and the other R1is iodo. In certain embodiments, one R1is fluoro and the other R1is iodo. In certain embodiments, X1is bromo. In certain embodiments, X1is chloro. In certain embodiments, X1is fluoro. In certain embodiments, X1is iodo. In - 46 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT certain embodiments, X3is alkylene. In certain embodiments, X3is -C(O)-. In certain embodiments, X3is. In certain embodiments, X3is. In certain embodiments, X3is an unsubstituted heterocycloalkylene. In certain embodiments, X3is a substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, haloalkyl, halogen, -C(O)-, or -SO2-. Other combinations or perturbations between R1, X1, and X3described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0164] In certain embodiments, provided herein are compounds represented by Formula Cmethyl, or ethyl; X1is bromo, chloro, fluoro, or iodo; and X2is oxygen. In certain embodiments, R3is hydrogen. In certain embodiments, R3is methyl. In certain embodiments, R3is ethyl. In certain embodiments, X1is bromo. In certain embodiments, X1is chloro. In certain embodiments, X1is fluoro. In certain embodiments, X1is iodo. Other combinations or perturbations between R3and X1described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0165] In certain embodiments, provided herein are compounds represented by Formula D,bromo, chloro, fluoro, or iodo.- 47 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT In certain embodiments, R2is. In certain embodiments, R2is. In certain embodiments, R2is. In certain embodiments, X1is bromo. In certain embodiments, X1is chloro. In certain embodiments, X1is fluoro. In certain embodiments, X1is iodo. Other combinations or perturbations between R2and X1described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0166] In certain embodiments, provided herein are compounds represented by Formula E, chloro, fluoro, or iodo. In certain embodiments, X1is bromo. In certain embodiments, X1is chloro. In certain embodiments, X1is fluoro. In certain embodiments, X1is iodo.

[0167] In certain embodiments, provided herein are compounds represented by Formula Ffurther wherein X1is bromo, chloro, fluoro, or iodo; X2is oxygen; X3is unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, haloalkyl, halogen, -C(O)-, or -SO2-; and X4is nitrogen wherein the R1bound to X4is absent. In certain embodiments, X1is bromo. In certain embodiments, X1is chloro. In certain embodiments, X1is fluoro. In certain embodiments, X1is iodo. - 48 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0168] In certain embodiments, provided herein are compounds represented by Formula Gfurther wherein X1is halogen; X2is -N(H)-, oxygen, or sulfur; and each n is independently zero, one, or two.

[0169] In certain embodiments, provided herein are compounds represented by Formula Hfurther wherein X1is bromo, chloro, fluoro, or iodo; X2is oxygen; X3is alkylene; -C(O)-;; ; or unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, haloalkyl, halogen, -C(O)-, or -SO2-; and X4is nitrogen wherein the R1bound to X4is absent. In certain embodiments, X1is bromo. In certain embodiments, X1is chloro. In certain embodiments, X1is fluoro. In certain embodiments, X1is iodo.

[0170] In certain embodiments, in combination with the embodiments, described in the paragraphs above, linkers (e.g., linker L described herein) are useful for linking PTMs and UTMs as described elsewhere herein. For example, in certain embodiments, linker L, as described herein, provides compounds having the following general structure PTM-L-UTM, wherein PTM represents a protein targeting moiety and UTM represents a ubiquitin ligase targeting moiety, as described elsewhere herein. Furthermore, the general structure PTM-L- UTM, compounds represented by Formula (I), A, B, C, D, E, F, G, or H and / or compounds represented by the following formula- 49 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT and are bifunctional compounds useful for modifying the ubiquitination and subsequent degradation of target proteins, target polypeptides, and fragments thereof. These bifunctional compounds described herein work in such way that the target protein / polypeptide is placed in proximity to a ubiquitin ligase to effect degradation (and inhibition) of the target protein / polypeptide.

[0171] In certain embodiments, in combination with the embodiments described in the paragraphs above, L is a bond. In certain embodiments, in combination with the embodiments- 50 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT- 51 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT- 52 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCTwherein each n1 is independently one, two, or three; each n2 is independently one, two, or three; each n3 is independently an integer from one to ten; each R9is independently hydrogen or alkyl; each R10is independently alkyl; R11is hydrogen, alkyl, hydroxymethyl, or haloalkyl; - 53 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT R12is hydrogen, an amino acid side chain, or R7is further bonded to R4to form proline; X6is NR9, oxygen, or sulfur; each X7is independently carbon or nitrogen; and aa is an integer from one to five.

[0172] In certain embodiments, in combination with the embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. Other combinations or perturbations between n1, n2, and n3 described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0173] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. Other combinations or perturbations between n1, n2, and n3 described in this paragraph are contemplated and are within the scope and spirit of this disclosure. - 54 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0174] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between n1, n2, n3, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0175] In certain embodiments, in combination with certatin embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. Other combinations or perturbations between n1, n2, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure. - 55 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0176] In certain embodiments, in combination with certain embodiments described in the paragraphs above, L isL5. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. Other combinations or perturbations between n3 and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0177] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between n1, n2, n3, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0178] In certain embodiments, in combination with certain embodiments described in the paragraphs above, L isL7. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. In certain embodiments, each R10is hydrogen. In certain - 56 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT embodiments, each R10is, independently, alkyl. In certain embodiments, one R10is hydrogen and the other R10is alkyl. In certain embodiments, R9and R10are further combinations of the embodiments described in this paragraph. In certain embodiments, each n3 is one. In certain embodiments, each n3 is two. In certain embodiments, each n3 is three. In certain embodiments, each n3 is four. In certain embodiments, each n3 is five. In certain embodiments, each n3 is six. In certain embodiments, each n3 is seven. In certain embodiments, each n3 is eight. In certain embodiments, each n3 is nine. In certain embodiments, each n3 is ten. In certain embodiments, one n3 is an integer from one to ten and the other n3 is a different integer from one to ten. Other combinations or perturbations between each n3, each R9, and each R10described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0179] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and n2 are one. In certain embodiments, each n1 and n2 are two. In certain embodiments, each n1 and n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, each ring containing the nitrogen is, independently, a four-membered ring; a five-membered ring; a six-membered ring; a seven- membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. Other combinations or perturbations between n1, n2, and n3 described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0180] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain - 57 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. In certain embodiments, n2 is one and n1 is two. In certain embodiments, n2 is one and n1 is three. In certain embodiments, n2 is two and n1 is three. Alternatively stated, in certain embodiments, the ring containing the two nitrogens is a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, R11is hydrogen. In certain embodiments, R11is alkyl. In certain embodiments, R11is hydroxymethyl. In certain embodiments, R11is haloalkyl. Other combinations or perturbations between n1, n2, and R11described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0181] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and n2 are one. In certain embodiments, each n1 and n2 are two. In certain embodiments, each n1 and n2 are three. In certain embodiments, each n1 is one and n2 is two. In certain embodiments, each n1 is one and n2 is three. In certain embodiments, each n1 is two and n2 is three. Alternatively stated, in certain embodiments, each ring is, independently, a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight- membered ring. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. Other combinations or perturbations between n1, n2, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0182] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. - 58 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT In certain embodiments, one R9is hydrogen and the other R9is alkyl. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. Other combinations or perturbations between n1, n2, n3, and each R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0183] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, each ring containing the nitrogen is, independently, a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between n1, n2, n3, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0184] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain - 59 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT embodiments, each n3 is one. In certain embodiments, each n3 is two. In certain embodiments, each n3 is three. In certain embodiments, each n3 is four. In certain embodiments, each n3 is five. In certain embodiments, each n3 is six. In certain embodiments, each n3 is seven. In certain embodiments, each n3 is eight. In certain embodiments, each n3 is nine. In certain embodiments, each n3 is ten. In certain embodiments, one n3 is an integer from one to ten and the other n3 is a different integer from one to ten. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. In certain embodiments, each R10is hydrogen. In certain embodiments, each R10is, independently, alkyl. In certain embodiments, one R10is hydrogen and the other R10is alkyl. In certain embodiments, R9and R10are further combinations of the embodiments described in this paragraph. Other combinations or perturbations between n1, n2, each n3, each R9, and each R10described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0185] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, each ring containing the nitrogen is, independently, a four-membered ring; a five-membered ring; a six- membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. Other combinations or perturbations between each n1, each n2, and n3 described in this paragraph are contemplated and are within the scope and spirit of this disclosure. - 60 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0186] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, each n2 is one and each n1 is two. In certain embodiments, each n2 is one and each n1 is three. In certain embodiments, each n2 is two and each n1 is three. In certain embodiments, each n1 is two, one n2 is two and the other n2 is one. In certain embodiments, each n2 is two, one n1 is two and the other n1 is one. Alternatively stated, in certain embodiments, the ring containing one nitrogen is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring; and the ring containing two nitrogens is a five-membered ring; a six-membered ring; a seven- membered ring; or an eight-membered ring. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between each n1, each n2, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0187] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, each n3 is one. In certain embodiments, each n3 is two. In certain embodiments, each n3 is three. In certain embodiments, each n3 is four. In certain embodiments, each n3 is five. In certain embodiments, each n3 is six. In certain embodiments, each n3 is seven. In certain embodiments, each n3 is eight. In certain embodiments, each n3 is nine. In certain - 61 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT embodiments, each n3 is ten. In certain embodiments, one n3 is an integer from one to ten and the other n3 is a different integer from one to ten. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. Other combinations or perturbations between n1, n2, each n3, and each R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0188] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, each ring containing the nitrogen is, independently, a five-membered ring; a six-membered ring; a seven- membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between each n1, each n2, n3, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0189] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, each n1 is one, a first n2 is one, the second - 62 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT n2 is two, and the third n2 is three. In certain embodiments, each n1 is two, a first n2 is one, the second n2 is two, and the third n2 is three. In certain embodiments, each n1 is three, a first n2 is one, the second n2 is two, and the third n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. And, in certain embodiments of the spirocycle, the spirocycle includes two four-membered rings; one four- membered ring and one five-membered ring; one four-membered ring and one six-membered ring; one four-membered ring and one seven-membered ring; one four-membered ring and one eight-membered ring; two five-membered rings; one five-membered ring and one six- membered ring; one five-membered ring and one seven-membered ring; one five-membered ring and one eight-membered ring; two six-membered rings; one six-membered ring and one seven-membered ring; one six-membered ring and one eight-membered ring; two seven- membered rings; one seven-membered ring and one eight-membered ring; or two eight- membered rings. Other combinations or perturbations between each n1 and each n2 described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0190] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, each ring containing the nitrogen is, independently, a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, X6is NR9. In one embodiment, R9is hydrogen. In one embodiment, R9is alkyl. In certain embodiments, X6is oxygen. In certain embodiments, X6is sulfur. Other combinations or perturbations between each n1, each n2, n3, - 63 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT X6, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0191] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, each n1 is one, a first n2 is one, the second n2 is two, and the third n2 is three. In certain embodiments, each n1 is two, a first n2 is one, the second n2 is two, and the third n2 is three. In certain embodiments, each n1 is three, a first n2 is one, the second n2 is two, and the third n2 is three. In certain embodiments, a first n1 is two, the second n1 is one, and the third n1 is one. Alternatively stated, in certain embodiments, the ring including only carbon is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. And, in certain embodiments of the spirocycle, the spirocycle includes two four-membered rings; one four-membered ring and one five-membered ring; one four-membered ring and one six-membered ring; one four-membered ring and one seven-membered ring; one four-membered ring and one eight-membered ring; two five-membered rings; one five-membered ring and one six-membered ring; one five- membered ring and one seven-membered ring; one five-membered ring and one eight- membered ring; two six-membered rings; one six-membered ring and one seven-membered ring; one six-membered ring and one eight-membered ring; two seven-membered rings; one seven-membered ring and one eight-membered ring; or two eight-membered rings. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between each n1, each n2, n3, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure. - 64 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0192] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen (i.e., the ring without X6) is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight- membered ring. In certain embodiments, each n3 is one. In certain embodiments, each n3 is two. In certain embodiments, each n3 is three. In certain embodiments, each n3 is four. In certain embodiments, each n3 is five. In certain embodiments, each n3 is six. In certain embodiments, each n3 is seven. In certain embodiments, each n3 is eight. In certain embodiments, each n3 is nine. In certain embodiments, each n3 is ten. In certain embodiments, one n3 is an integer from one to ten and the other n3 is a different integer from one to ten. In certain embodiments, X6is NR9. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. In certain embodiments, X6is -NH. In certain embodiments, X6is N- alkyl. In certain embodiments, X6is oxygen. In certain embodiments, X6is sulfur. Other combinations or perturbations between n1, n2, each n3, X6, and each R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0193] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, each ring containing the nitrogen is, independently, a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, R9is hydrogen. In certain - 65 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT embodiments, R9is alkyl. In certain embodiments, R12is hydrogen. In certain embodiments, R12is an amino acid side chain as described elsewhere herein. In certain embodiments, R9is further bonded to R12to form proline. In certain embodiments, aa is one. In certain embodiments, aa is two. In certain embodiments, aa is three. In certain embodiments, aa is four. In certain embodiments, aa is five. Other combinations or perturbations between each n1, each n2, R9, R12, and aa described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0194] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, each n1 is one, a first n2 is one, and the second n2 is two. In certain embodiments, each n1 is two, a first n2 is one, and the second n2 is two. In certain embodiments, each n1 is three, a first n2 is one, and the second n2 is two. In certain embodiments, a first n1 is two, the second n1 is one, and each n2 is one. Alternatively stated, in certain embodiments of the spirocycle, the spirocycle includes two four-membered rings; one four-membered ring and one five-membered ring; one four-membered ring and one six-membered ring; one four-membered ring and one seven-membered ring; one four- membered ring and one eight-membered ring; two five-membered rings; one five-membered ring and one six-membered ring; one five-membered ring and one seven-membered ring; one five-membered ring and one eight-membered ring; two six-membered rings; one six-membered ring and one seven-membered ring; one six-membered ring and one eight-membered ring; two seven-membered rings; one seven-membered ring and one eight-membered ring; or two eight- membered rings. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. In certain embodiments, R12is hydrogen. In certain embodiments, R12is an amino acid side chain as described elsewhere herein. In certain embodiments, R9is further bonded to R12to form proline. In certain embodiments, aa is one. In certain embodiments, aa is two. In certain embodiments, aa is three. In certain embodiments, aa is four. In certain embodiments, aa is - 66 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT five. Other combinations or perturbations between each n1, each n2, R9, R12, and aa described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0195] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, each n1 is one, a first n2 is one, the second n2 is two, and the third n2 is three. In certain embodiments, each n1 is two, a first n2 is one, the second n2 is two, and the third n2 is three. In certain embodiments, each n1 is three, a first n2 is one, the second n2 is two, and the third n2 is three. In certain embodiments, a first n1 is two, the second n1 is one, the third n1 is one, a first n2 is two, the second n2 is two, and the third n2 is one. Alternatively stated, in certain embodiments, the ring containing the nitrogen and X7is a four-membered ring; a five-membered ring; a six-membered ring; a seven- membered ring; or an eight-membered ring. And, in certain embodiments of the spirocycle, the spirocycle includes two four-membered rings; one four-membered ring and one five-membered ring; one four-membered ring and one six-membered ring; one four-membered ring and one seven-membered ring; one four-membered ring and one eight-membered ring; two five- membered rings; one five-membered ring and one six-membered ring; one five-membered ring and one seven-membered ring; one five-membered ring and one eight-membered ring; two six- membered rings; one six-membered ring and one seven-membered ring; one six-membered ring and one eight-membered ring; two seven-membered rings; one seven-membered ring and one eight-membered ring; or two eight-membered rings. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, X7is carbon. In certain embodiments, X7is nitrogen. Other combinations or perturbations between each n1, each n2, n3, and X7described in this paragraph are contemplated and are within the scope and spirit of this disclosure. - 67 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0196] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is one. Alternatively stated, in certain embodiments, the ring containing the nitrogen is a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. In certain embodiments, R12is hydrogen. In certain embodiments, R12is an amino acid side chain as described elsewhere herein. In certain embodiments, R9is further bonded to R12to form proline. In certain embodiments, aa is one. In certain embodiments, aa is two. In certain embodiments, aa is three. In certain embodiments, aa is four. In certain embodiments, aa is five. Other combinations or perturbations between n1, n2, n3, R9, R12, and aa described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0197] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, each n1 is one, a first n2 is one, the second n2 is two, and the third n2 is two. In certain embodiments, each n1 is two, a first n2 is one, the second n2 is two, and the third n2 is two. In certain embodiments, each n1 is three, a first n2 - 68 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT is one, the second n2 is two, and the third n2 is two. In certain embodiments, a first n1 is two, the second n1 is one, the third n1 is one, a first n2 is two, the second n2 is one, and the third n2 is one. Alternatively stated, in certain embodiments, the ring containing the nitrogen and X7is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. And, in certain embodiments, each ring containing the nitrogen (i.e., collectively the fused rings without X7) is, independently, a five-membered ring; a six- membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, X7is carbon. In certain embodiments, X7is nitrogen. Other combinations or perturbations between each n1, each n2, n3, and X7described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0198] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, each n1 is one, a first n2 is two, and the second n2 is one. Alternatively stated, in certain embodiments of the spirocycle, the spirocycle includes two four-membered rings; one four-membered ring and one five-membered ring; one four-membered ring and one six-membered ring; one four-membered ring and one seven- membered ring; one four-membered ring and one eight-membered ring; two five-membered rings; one five-membered ring and one six-membered ring; one five-membered ring and one seven-membered ring; one five-membered ring and one eight-membered ring; two six- membered rings; one six-membered ring and one seven-membered ring; one six-membered ring and one eight-membered ring; two seven-membered rings; one seven-membered ring and one eight-membered ring; or two eight-membered rings. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain - 69 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, X6is NR9. In one embodiment, R9is hydrogen. In one embodiment, R9is alkyl. In certain embodiments, X6is oxygen. In certain embodiments, X6is sulfur. Other combinations or perturbations between each n1, each n2, n3, and X6described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0199] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, each n1 is one, a first n2 is two, and the second n2 is one. Alternatively stated, in certain embodiments of the spirocycle, the spirocycle includes two four-membered rings; one four-membered ring and one five-membered ring; one four-membered ring and one six-membered ring; one four-membered ring and one seven- membered ring; one four-membered ring and one eight-membered ring; two five-membered rings; one five-membered ring and one six-membered ring; one five-membered ring and one seven-membered ring; one five-membered ring and one eight-membered ring; two six- membered rings; one six-membered ring and one seven-membered ring; one six-membered ring and one eight-membered ring; two seven-membered rings; one seven-membered ring and one eight-membered ring; or two eight-membered rings. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between each n1, each n2, n3, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure. - 70 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0200] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, each ring containing the nitrogen is, independently, a four-membered ring; a five-membered ring; a six-membered ring; a seven- membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. Other combinations or perturbations between each n1, each n2, n3, and each R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0201] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, each n3 is one. In certain embodiments, each n3 is two. In certain embodiments, each n3 is three. In certain embodiments, each n3 is four. In certain embodiments, each n3 is - 71 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT five. In certain embodiments, each n3 is six. In certain embodiments, each n3 is seven. In certain embodiments, each n3 is eight. In certain embodiments, each n3 is nine. In certain embodiments, each n3 is ten. In certain embodiments, one n3 is an integer from one to ten and the other n3 is a different integer from one to ten. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, a first R9is hydrogen, the second R9is alkyl, and the third R9is hydrogen. In certain embodiments, a first R9is hydrogen, the second R9is alkyl, and the third R9is alkyl. Other combinations or perturbations between n1, n2, each n3, and each R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0202] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, each n1 is one, a first n2 is one, and the second n2 is two. In certain embodiments, each n1 is two, a first n2 is one, and the second n2 is two. In certain embodiments, each n1 is three, a first n2 is one, and the second n2 is two. In certain embodiments, a first n1 is two, the second n1 is one, a first n2 is two, and the second n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen and X7is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. And, in certain embodiments, the ring containing the nitrogen (i.e., the ring without X7) is a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, each n3 is one. In certain embodiments, each n3 is two. In certain embodiments, each n3 is three. In certain embodiments, each n3 is four. In certain embodiments, each n3 is five. In certain embodiments, each n3 is six. In certain embodiments, each n3 is seven. In certain embodiments, each n3 is eight. In certain embodiments, each n3 is nine. In certain embodiments, each n3 is ten. In certain embodiments, one n3 is an integer from one to ten and the other n3 is a different integer from one to ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. In certain embodiments, X7is carbon. In certain embodiments, X7is nitrogen. Other - 72 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT combinations or perturbations between each n1, each n2, each n3, R9, and X7described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0203] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, the ring containing only carbon is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. And, in certain embodiments, the ring containing the nitrogen is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, each n3 is one. In certain embodiments, each n3 is two. In certain embodiments, each n3 is three. In certain embodiments, each n3 is four. In certain embodiments, each n3 is five. In certain embodiments, each n3 is six. In certain embodiments, each n3 is seven. In certain embodiments, each n3 is eight. In certain embodiments, each n3 is nine. In certain embodiments, each n3 is ten. In certain embodiments, one n3 is an integer from one to ten and the other n3 is a different integer from one to ten. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. Other combinations or perturbations between each n1, each n2, each n3, and each R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0204] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen is a four-membered ring; a five-membered ring; - 73 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. In certain embodiments, R12is hydrogen. In certain embodiments, R12is an amino acid side chain as described elsewhere herein. In certain embodiments, R9is further bonded to R12to form proline. In certain embodiments, aa is one. In certain embodiments, aa is two. In certain embodiments, aa is three. In certain embodiments, aa is four. In certain embodiments, aa is five. Other combinations or perturbations between n1, n2, n3, each R9, R12, and aa described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0205] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen and X7is a four-membered ring; a five-membered ring; a six-membered ring; a seven- membered ring; or an eight-membered ring. And, in certain embodiments, the ring containing the nitrogen (i.e., the ring without X7) is a four-membered ring; a five-membered ring; a six- membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, each n3 is one. In certain embodiments, each n3 is two. In certain embodiments, each n3 is three. In certain embodiments, each n3 is four. In certain embodiments, each n3 is five. In certain embodiments, each n3 is six. In certain embodiments, each n3 is seven. In certain embodiments, each n3 is eight. In certain embodiments, each n3 is nine. In certain embodiments, each n3 is ten. In certain embodiments, one n3 is an integer from one to ten and the other n3 is a different integer from one to ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. In certain embodiments, X7is carbon. In certain - 74 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT embodiments, X7is nitrogen. Other combinations or perturbations between each n1, each n2, each n3, R9, and X7described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0206] In certain embodiments, in combination with certain embodiments described in thecertain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, each n1 is one, a first n2 is one, the second n2 is two, and the third n2 is two. In certain embodiments, each n1 is two, a first n2 is one, second n2 is two, and the third n2 is three. In certain embodiments, each n1 is three, a first n2 is one, the second n2 is two, and the third n2 is three. In certain embodiments, a first n1 is two, the second n1 is one, the third n1 is one, a first n2 is two, the second n2 is one, and the third n2 is one. Alternatively stated, in certain embodiments, the ring containing only carbon is a four-membered ring; a five-membered ring; a six-membered ring; a seven- membered ring; or an eight-membered ring. And, in certain embodiments, each ring containing the nitrogen (i.e., collectively the fused rings) is, independently, a five-membered ring; a six- membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between each n1, each n2, n3, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0207] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are - 75 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen (i.e., the ring without X6) is, independently, a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, each n3 is one. In certain embodiments, each n3 is two. In certain embodiments, each n3 is three. In certain embodiments, each n3 is four. In certain embodiments, each n3 is five. In certain embodiments, each n3 is six. In certain embodiments, each n3 is seven. In certain embodiments, each n3 is eight. In certain embodiments, each n3 is nine. In certain embodiments, each n3 is ten. In certain embodiments, one n3 is an integer from one to ten and the other n3 is a different integer from one to ten. In certain embodiments, X6is NR9. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. In certain embodiments, X6is -NH. In certain embodiments, X6is N- alkyl. In certain embodiments, X6is oxygen. In certain embodiments, X6is sulfur. Other combinations or perturbations between n1, n2, each n3, X6, and each R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0208] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, each n1 is one, a first n2 is one, the second n2 is two, and the third n2 is two. In certain embodiments, each n1 is two, a first n2 is one, the second n2 is two, and the third n2 is two. In certain embodiments, each n1 is three, a first n2 is one, the second n2 is two, and the third n2 is two. In certain embodiments, a first n1 is one, the second n1 is one, the third n1 is one, a first n2 is three, the second n2 is one, and the third n2 is one. Alternatively stated, in certain embodiments, the ring containing the nitrogen (i.e., not the ring(s) in the fused ring system) is a four-membered ring; a five-membered ring; a six- membered ring; a seven-membered ring; or an eight-membered ring. And, in certain - 76 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT embodiments, each ring containing the nitrogen (i.e., collectively the fused rings) is, independently, a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. Other combinations or perturbations between each n1, each n2, and each n3 described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0209] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, the ring containing only carbon is a four-membered ring; a five-membered ring; a six-membered ring; a seven- membered ring; or an eight-membered ring. And, in certain embodiments, the ring containing the nitrogen is a four-membered ring; a five-membered ring; a six-membered ring; a seven- membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, a first R9is hydrogen, the second R9is alkyl, and the third R9is hydrogen. In certain embodiments, a first R9is hydrogen, the second R9is alkyl, and the third R9is alkyl. Other combinations or perturbations between each n1, each n2, n3, and each R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0210] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In - 77 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen is a four membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, a first R9is hydrogen, the second R9is alkyl, and the third R9is hydrogen. In certain embodiments, a first R9is hydrogen, the second R9is alkyl, and the third R9is alkyl. In certain embodiments, R12is hydrogen. In certain embodiments, R12is an amino acid side chain as described elsewhere herein. In certain embodiments, R9is further bonded to R12to form proline. In certain embodiments, aa is one. In certain embodiments, aa is two. In certain embodiments, aa is three. In certain embodiments, aa is four. In certain embodiments, aa is five. Other combinations or perturbations between n1, n2, each R9, R12, and aa described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0211] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen and X7is a four-membered ring; a five-membered ring; a six-membered ring; a seven- membered ring; or an eight-membered ring. And, in certain embodiments, the ring containing the nitrogen (i.e., the ring without X7) is a four-membered ring; a five-membered ring; a six- membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. In certain embodiments, X7is carbon. In certain embodiments, X7is nitrogen. Other combinations or perturbations between each n1, each n2, - 78 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT n3, each R9, and X7described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0212] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, a first n1 is one, the second n1 is two, and each n2 is two. Alternatively stated, in certain embodiments, the ring containing the nitrogen (i.e., the ring without X6) is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. And, in certain embodiments, the ring containing the nitrogren and X6is a five-membered ring; a six-membered ring; a seven- membered ring; or an eight-membered ring. In certain embodiments, each n3 is one. In certain embodiments, each n3 is two. In certain embodiments, each n3 is three. In certain embodiments, each n3 is four. In certain embodiments, each n3 is five. In certain embodiments, each n3 is six. In certain embodiments, each n3 is seven. In certain embodiments, each n3 is eight. In certain embodiments, each n3 is nine. In certain embodiments, each n3 is ten. In certain embodiments, X6is NR9. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, a first R9is hydrogen, the second R9is alkyl, and the third R9is hydrogen. In certain embodiments, a first R9is hydrogen, the second R9is alkyl, and the third R9is alkyl. In certain embodiments, X6is -NH. In certain embodiments, X6is N-alkyl. In certain embodiments, X6is oxygen. In certain embodiments, X6is sulfur. Other combinations or perturbations between each n1, each n2, n3, X6, and each R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0213] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In - 79 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, a first R9is hydrogen, the second R9is alkyl, and the third R9is hydrogen. In certain embodiments, a first R9is hydrogen, the second R9is alkyl, and the third R9is alkyl. In certain embodiments, each R10is hydrogen. In certain embodiments, each R10is, independently, alkyl. In certain embodiments, one R10is hydrogen and the other R10is alkyl. In certain embodiments, R9and R10are further combinations of the embodiments described in this paragraph. Other combinations or perturbations between n1, n2, each R9, and each R10described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0214] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. In certain embodiments, n2 is one and n1 is two. In certain embodiments, n2 is one and n1 is three. In certain embodiments, n2 is two and n1 is three. Alternatively stated, in certain embodiments, the ring containing the two nitrogens is a five-membered ring; a six-membered ring; a seven-membered ring; or an eight- membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. Other combinations or perturbations between n1, n2, n3, and each R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure. - 80 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0215] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, each n2 is one and each n1 is two. In certain embodiments, each n2 is one and each n1 is three. In certain embodiments, each n2 is two and each n1 is three. In certain embodiments, a first n1 is two, the second n1 is one, and each n2 is two. Alternatively stated, in certain embodiments, the ring containing nitrogen (i.e., the ring without X7) is a four-membered ring; a five-membered ring; a six-membered ring; a seven- membered ring; or an eight-membered ring. And, in certain embodiments, the ring containing nitrogen and X7is a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. In certain embodiments, X7is carbon. In certain embodiments, X7is nitrogen. Other combinations or perturbations between each n1, each n2, R9, and X7described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0216] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, each n2 is one and each n1 is two. In certain embodiments, each n2 is one and each n1 is three. In certain embodiments, each n2 is two and each n1 is three. In certain embodiments, a first n1 is two, the second n1 is one, and each n2 is two. Alternatively stated, in certain embodiments, the ring containing only carbon is a four- membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an - 81 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT eight-membered ring. And, in certain embodiments, the ring containing nitrogen and X7is a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. In certain embodiments, X7is carbon. In certain embodiments, X7is nitrogen. Other combinations or perturbations between each n1, each n2, n3, each R9, and X7described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0217] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 is two and n2 is three. In certain embodiments, n1 is three and n2 is two. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is one. Alternatively stated, in certain embodiments, the ring containing the two nitrogens is a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. In certain embodiments, R12is hydrogen. In certain embodiments, R12is an amino acid side chain as described elsewhere herein. In certain embodiments, R9is further bonded to R12to form proline. In certain embodiments, aa is one. In certain embodiments, aa is two. In certain embodiments, aa is three. In certain embodiments, aa is four. In certain embodiments, aa is five. Other combinations or perturbations between n1, n2, each R9, R12, and aa described in this paragraph are contemplated and are within the scope and spirit of this disclosure. - 82 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0218] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, each n1 is one, a first n2 is one, and the second n2 is two. In certain embodiments, each n1 is two, a first n2 is one, and the second n2 is two. In certain embodiments, each n1 is three, a first n2 is one, and the second n2 is two. In certain embodiments, a first n1 is two, the second n1 is one, and each n2 is two. Alternatively stated, in certain embodiments, the first ring containing the nitrogen and X7is a four-membered ring; a five-membered ring; a six-membered ring; a seven- membered ring; or an eight-membered ring. And, in certain embodiments, the second ring containing the nitrogen further bearing R9as a substituent is a five-membered ring; a six- membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. In certain embodiments, each X7is carbon. In certain embodiments, each X7is nitrogen. In certain embodiments, one X7is carbon and the other X7is nitrogen. Other combinations or perturbations between each n1, each n2, n3, R9, and each X7described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0219] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, - 83 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, each n1 is one, a first n2 is one, and the second n2 is two. In certain embodiments, each n1 is two, a first n2 is one, and the second n2 is two. In certain embodiments, each n1 is three, a first n2 is one, and the second n2 is two. In certain embodiments, a first n1 is two, the second n1 is one, a first n2 is one, and the second n2 is two. Alternatively stated, in certain embodiments, the ring containing the nitrogen and X6is a five-membered ring; a six-membered ring; a seven- membered ring; or an eight-membered ring. And, in certain embodiments, the ring containing the nitrogen and X7is a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. In certain embodiments, X6is NR9. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. In certain embodiments, X6is oxygen. In certain embodiments, X6is sulfur. In certain embodiments, X7is carbon. In certain embodiments, X7is nitrogen. Other combinations or perturbations between each n1, each n2, n3, each R9, X6, and X7described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0220] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, each ring containing the nitrogen is, independently, a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain - 84 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. Other combinations or perturbations between each n1, each n2, and n3 described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0221] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, each ring containing the nitrogen is, independently, a four-membered ring; a five-membered ring; a six- membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, each n3 is one. In certain embodiments, each n3 is two. In certain embodiments, each n3 is three. In certain embodiments, each n3 is four. In certain embodiments, each n3 is five. In certain embodiments, each n3 is six. In certain embodiments, each n3 is seven. In certain embodiments, each n3 is eight. In certain embodiments, each n3 is nine. In certain embodiments, each n3 is ten. In certain embodiments, one n3 is an integer from one to ten and the other n3 is a different integer from one to ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between each n1, each n2, each n3, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0222] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain - 85 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, each ring containing the nitrogen is, independently, a four-membered ring; a five-membered ring; a six- membered ring; a seven-membered ring; or an eight-membered ring. And, in certain embodiments, the ring containing only carbon is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, each n3 is one. In certain embodiments, each n3 is two. In certain embodiments, each n3 is three. In certain embodiments, each n3 is four. In certain embodiments, each n3 is five. In certain embodiments, each n3 is six. In certain embodiments, each n3 is seven. In certain embodiments, each n3 is eight. In certain embodiments, each n3 is nine. In certain embodiments, each n3 is ten. In certain embodiments, one n3 is an integer from one to ten and the other n3 is a different integer from one to ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between each n1, each n2, each n3, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0223] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, each ring containing the nitrogen is, independently, a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. In certain embodiments, R12is hydrogen. In certain embodiments, R12is an amino acid side chain as described elsewhere herein. In certain - 86 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT embodiments, R9is further bonded to R12to form proline. In certain embodiments, aa is one. In certain embodiments, aa is two. In certain embodiments, aa is three. In certain embodiments, aa is four. In certain embodiments, aa is five. Other combinations or perturbations between each n1, each n2, n3, R9, R12, and aa described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0224] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, each ring containing a nitrogen (i.e., each ring containing a nitrogen with or without X7) is, independently, a four-membered ring; a five-membered ring; a six-membered ring; a seven- membered ring; or an eight-membered ring. And, in certain embodiments, the ring containing only carbon is a four-membered ring; a five-membered ring; a six-membered ring; a seven- membered ring; or an eight-membered ring. In certain embodiments, each n3 is one. In certain embodiments, each n3 is two. In certain embodiments, each n3 is three. In certain embodiments, each n3 is four. In certain embodiments, each n3 is five. In certain embodiments, each n3 is six. In certain embodiments, each n3 is seven. In certain embodiments, each n3 is eight. In certain embodiments, each n3 is nine. In certain embodiments, each n3 is ten. In certain embodiments, one n3 is an integer from one to ten and the other n3 is a different integer from one to ten. In certain embodiments, X7is carbon. In certain embodiments, X7is nitrogen. Other combinations or perturbations between each n1, each n2, each n3, and X7described in this paragraph are contemplated and are within the scope and spirit of this disclosure. - 87 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0225] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, each n1 is one, a first n2 is one, the second n2 is two, and the third n2 is three. In certain embodiments, each n1 is two, a first n2 is one, the second n2 is two, and the third n2 is three. In certain embodiments, a first n1 is two, the second n1 is two, the third n1 is two, a first n2 is one, the second n2 is two, and the third n2 is two. Alternatively stated, in certain embodiments, each ring containing a nitrogen (i.e., each ring without X6) is, independently, a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. And, in certain embodiments, the ring containing nitrogen and X6is a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, each n3 is one. In certain embodiments, each n3 is two. In certain embodiments, each n3 is three. In certain embodiments, each n3 is four. In certain embodiments, each n3 is five. In certain embodiments, each n3 is six. In certain embodiments, each n3 is seven. In certain embodiments, each n3 is eight. In certain embodiments, each n3 is nine. In certain embodiments, each n3 is ten. In certain embodiments, one n3 is an integer from one to ten and the other n3 is a different integer from one to ten. In certain embodiments, X6is NR9. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. In certain embodiments, X6is oxygen. In certain embodiments, X6is sulfur. Other combinations or perturbations between each n1, each n2, each n3, X6, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0226] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each - 88 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, each ring containing the nitrogen is, independently, a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between each n1, each n2, n3, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0227] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, a first n1 is two, the second n1 is one, a first n2 is two, and the second n2 is three. Alternatively stated, in certain embodiments, the ring containing only carbon is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. And, in certain embodimenst, the ring containing nitrogen is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, each n3 is one. In certain embodiments, each n3 is two. In certain embodiments, each n3 is three. In certain embodiments, each n3 is four. In certain embodiments, each n3 is five. In certain embodiments, each n3 is six. In certain embodiments, each n3 is seven. In certain embodiments, each n3 is eight. In certain embodiments, each n3 is nine. In certain embodiments, each n3 is ten. In certain embodiments, one n3 is an integer from one to ten and the other n3 is a different integer from one to ten. In certain embodiments, each R9is hydrogen. In certain embodiments, each - 89 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. Other combinations or perturbations between each n1, each n2, each n3, and each R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0228] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. In certain embodiments, n2 is one and n1 is two. In certain embodiments, n2 is one and each n1 is three. In certain embodiments, n2 is two and n1 is three. In certain embodiments, n1 is two, and n2 is one. Alternatively stated, in certain embodiments, the ring is a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, R11is hydrogen. In certain embodiments, R11is alkyl. In certain embodiments, R11is hydroxymethyl. In certain embodiments, R11is haloalkyl. Other combinations or perturbations between n1, n2, and R11described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0229] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. In certain embodiments, n2 is one and n1 is two. In certain embodiments, n2 is one and each n1 is three. In certain embodiments, n2 is two and n1 is three. In certain embodiments, n1 is two, and n2 is one. Alternatively stated, in certain embodiments, the ring is a five- membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between n1, n2, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure. - 90 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0230] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between n1, n2, n3, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0231] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, each R9is hydrogen. In certain embodiments, each R9is, independently, alkyl. In certain embodiments, one R9is hydrogen and the other R9is alkyl. Other combinations or perturbations between n1, n2, and each R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure. - 91 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0232] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. In certain embodiments, R12is hydrogen. In certain embodiments, R12is an amino acid side chain as described elsewhere herein. In certain embodiments, R9is further bonded to R12to form proline. In certain embodiments, aa is one. In certain embodiments, aa is two. In certain embodiments, aa is three. In certain embodiments, aa is four. In certain embodiments, aa is five. Other combinations or perturbations between R9, R12, and aa described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0233] In certain embodiments, in combination with certain embodiments described in the paragraphs above, L is L62. In certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between n1, n2, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0234] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. Alternatively stated, in certain embodiments, the rings containing - 92 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT nitrogen are, independently, a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, X6is NR9. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. In certain embodiments, X6is -NH. In certain embodiments, X6is N-alkyl. In certain embodiments, X6is oxygen. In certain embodiments, X6is sulfur. Other combinations or perturbations between each n1, each n2, n3, X6, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0235] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and each n2 is one. In certain embodiments, n1 is two, a first n2 is two, and the second n2 is two. In certain embodiments, n1 is two, a first n2 is two, and the second n2 is 3. In certain embodiments, n1 is one, a first n2 is one, and the second n2 is two. Other combinations or perturbations between n1 and each n2 described in this paragraph to make alternative bicyclics are contemplated and are within the scope and spirit of this disclosure.

[0236] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, a first n1 is two, the second n1 is one, a first n2 is two, and the second n2 is three. Alternatively stated, in certain embodiments, each ring containing the nitrogen is, independently, a four-membered ring; a five-membered ring; a six- membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain - 93 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. Other combinations or perturbations between each n1, each n2, and n3 described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0237] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. embodiments, each n1 and each n2 are one. In certain embodiments, each n1 and each n2 are two. In certain embodiments, each n1 and each n2 are three. In certain embodiments, each n1 is one and each n2 is two. In certain embodiments, each n1 is one and each n2 is three. In certain embodiments, each n1 is two and each n2 is three. In certain embodiments, a first n1 is two, the second n1 is one, a first n2 is two, and the second n2 is three. Alternatively stated, in certain embodiments, ring containing only carbon is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. And, in certain embodiments, the ring containing nitrogen is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between each n1, each n2, n3, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0238] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is - 94 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT three. Alternatively stated, in certain embodiments, the ring containing the nitrogen is a four membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. In certain embodiments, R12is hydrogen. In certain embodiments, R12is an amino acid side chain as described elsewhere herein. In certain embodiments, R9is further bonded to R12to form proline. In certain embodiments, aa is one. In certain embodiments, aa is two. In certain embodiments, aa is three. In certain embodiments, aa is four. In certain embodiments, aa is five. Other combinations or perturbations between n1, n2, n3, R9, R12, and aa described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0239] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. Alternatively stated, in certain embodiments of the spirocycle, the spirocycle includes one three-membered ring and one four-membered ring; two four-membered rings; one four-membered ring and one five-membered ring; one four- membered ring and one six-membered ring; one four-membered ring and one seven-membered ring; one four-membered ring and one eight-membered ring; one four-membered ring and one nine-membered ring; one four-membered ring and one ten-membered ring; one four-membered ring and one eleven-membered ring; one four-membered ring and one twelve-membered ring; two five-membered rings; one five-membered ring and one six-membered ring; one five- membered ring and one seven-membered ring; one five-membered ring and one eight- membered ring; one five-membered ring and one-nine-membered ring; one five-membered - 95 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT ring and one ten-membered ring; one five-membered ring and one eleven-membered ring; one five-membered ring and one twelve-membered ring; two six-membered rings; one six- membered ring and one seven-membered ring; one six-membered ring and one eight- membered ring; one six-membered ring and one-nine-membered ring; one six-membered ring and one ten-membered ring; one six-membered ring and one eleven-membered ring; one six- membered ring and one twelve-membered ring; two seven-membered rings; one seven- membered ring and one eight-membered ring; one seven-membered ring and one-nine- membered ring; one seven-membered ring and one ten-membered ring; one seven-membered ring and one eleven-membered ring; one seven-membered ring and one twelve-membered ring; two eight-membered rings; one eight-membered ring and one-nine-membered ring; one eight- membered ring and one ten-membered ring; one eight-membered ring and one eleven- membered ring; or one eight-membered ring and one twelve-membered ring. Other combinations or perturbations between n1, n2, and n3 described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0240] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between n1, n2, and R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0241] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, each n1 and n2 are one. In certain embodiments, each n1 and n2 are two. In certain embodiments, each n1 and - 96 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT n2 are three. In certain embodiments, each n1 is one and n2 is two. In certain embodiments, each n1 is one and n2 is three. In certain embodiments, each n1 is two and n2 is three. Alternatively stated, in certain embodiments, each ring (i.e., the ring containing only carbon and the ring containing nitrogen) is, independently, a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, R9is hydrogen. In certain embodiments, R9is alkyl. Other combinations or perturbations between each n1, each n2, R9described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0242] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. In certain embodiments, n3 is one. In certain embodiments, n3 is two. In certain embodiments, n3 is three. In certain embodiments, n3 is four. In certain embodiments, n3 is five. In certain embodiments, n3 is six. In certain embodiments, n3 is seven. In certain embodiments, n3 is eight. In certain embodiments, n3 is nine. In certain embodiments, n3 is ten. Other combinations or perturbations between n1, n2, and n3 described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0243] In certain embodiments, in combination with certain embodiments described in the paragraphs above,. certain embodiments, n1 and n2 are one. In certain embodiments, n1 and n2 are two. In certain embodiments, n1 and n2 are three. In certain embodiments, n1 is one and n2 is two. In certain embodiments, n1 is one and n2 is three. In certain embodiments, n1 is two and n2 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen is a four-membered ring; a five-membered ring; a six-membered ring; a seven-membered ring; or an eight-membered ring. Other combinations - 97 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT or perturbations between n1 and n2 described in this paragraph are contemplated and are within the scope and spirit of this disclosure.

[0244] In certain embodiments, in combination with embodiments described in the- 98 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT ,- 99 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT. ,. ,. , - 100 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT- 101 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT- 102 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT- 103 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0245] In certain embodiments, the compound is selected from the group consisting of 1- [4-(4-{[(3S)-3-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl]oxy}phenyl)-4-methylpiperazin-1-yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3- diazinane-2,4-dione (23); (3S)-3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3,3-difluoropiperidin-1-yl)methyl)-4- fluoropiperidin-1-yl)phenyl)piperidine-2,6-dione (135); (R)-3-(4-(4-((4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)piperidin-1- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (140); (S)-3-(3-(4-((4-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)piperidin-1- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (141); (3R)-3-(4-(4-((4-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3,3- difluoropiperidin-1-yl)methyl)piperidin-1-yl)-2,5-difluorophenyl)piperidine-2,6-dione (246); (3R)-3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin- 7-yl)oxy)phenyl)-3,3-difluoropiperidin-1-yl)methyl)piperidin-1-yl)-2,6- difluorophenyl)piperidine-2,6-dione (263); 1-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H- - 104 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2-(trifluoromethyl)piperidin-1- yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (264); (3R)-3-(4-(4- ((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)-2-(trifluoromethyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine- 2,6-dione (265); (3R)-3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3,3-difluoropiperidin-1-yl)methyl)piperidin-1-yl)- 2,3-difluorophenyl)piperidine-2,6-dione (266); (3R)-3-(4-(4-((4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3,3- difluoropiperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (267); 1-(4-(4-((4- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)- 3,3-difluoropiperidin-1-yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)- dione (272); (S)-3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)phenyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (279); (S)-1-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1-yl)methyl)piperidin-1- yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (280); (S)-1-(4-(4-((4-(4-((6-bromo-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1- yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (281); 1-(4-(4-((4-(4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)- 3,3-dimethylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)- dione (282); (S)-1-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)phenyl)-2-isopropylpiperazin-1-yl)methyl)piperidin-1- yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (283); 1-(4-(4-((4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2,2- dimethylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (284); 1-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin- 7-yl)oxy)phenyl)-3-oxopiperazin-1-yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine- 2,4(1H,3H)-dione (285); (S)-1-(4-(4-((2-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)morpholino)methyl)piperidin-1- yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (288); (S)-3-(4-(4-(((S)-2-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)morpholino)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (289); (S)-1-(3- (4-((2-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- - 105 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT yl)oxy)phenyl)morpholino)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)- dione (290); (R)-3-(4-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,5- difluorophenyl)piperidine-2,6-dione (291); (R)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1- yl)methyl)piperidin-1-yl)-2,5-difluorophenyl)piperidine-2,6-dione (292); rac-(3R)-3-[4-(4- {[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl]oxy}benzenesulfonyl)piperazin-1-yl]methyl}piperidin-1-yl)-2,5- difluorophenyl]piperidine-2,6-dione (293); rac-(3R)-3-[4-(4-{[4-(4-{[6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}benzenesulfonyl)piperidin-1- yl]methyl}piperidin-1-yl)-2,5-difluorophenyl]piperidine-2,6-dione (294); (R)-3-(4-(4-(((S)-4- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)- 2-methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,5-difluorophenyl)piperidine-2,6-dione (295); (R)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,5- difluorophenyl)piperidine-2,6-dione (296); (R)-3-(4-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1- yl)methyl)piperidin-1-yl)-2,6-difluorophenyl)piperidine-2,6-dione (297); (R)-3-(4-(4-(((R)-4- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)- 2-methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,6-difluorophenyl)piperidine-2,6-dione (298); (R)-3-(4-(4-((4-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)phenyl)sulfonyl)piperazin-1-yl)methyl)piperidin-1-yl)-2,6- difluorophenyl)piperidine-2,6-dione (299); (R)-3-(4-(4-((4-((4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)sulfonyl)piperidin-1- yl)methyl)piperidin-1-yl)-2,6-difluorophenyl)piperidine-2,6-dione (300); (R)-3-(4-(4-(((S)-4- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)- 2-methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,6-difluorophenyl)piperidine-2,6-dione (301); (R)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,6- difluorophenyl)piperidine-2,6-dione (302); (S)-3-(4-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1- yl)methyl)-4-fluoropiperidin-1-yl)phenyl)piperidine-2,6-dione (303); (S)-3-(4-(4-(((R)-4-(4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2- - 106 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT methylpiperazin-1-yl)methyl)-4-fluoropiperidin-1-yl)phenyl)piperidine-2,6-dione (304); (S)- 3-(4-(4-((4-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)sulfonyl)piperazin-1-yl)methyl)-4-fluoropiperidin-1-yl)phenyl)piperidine-2,6- dione (305); (S)-3-(4-(4-((4-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)phenyl)sulfonyl)piperidin-1-yl)methyl)-4-fluoropiperidin-1- yl)phenyl)piperidine-2,6-dione (306); (S)-3-(4-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1-yl)methyl)-4- fluoropiperidin-1-yl)phenyl)piperidine-2,6-dione (307); (S)-3-(4-(4-(((R)-4-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3- methylpiperazin-1-yl)methyl)-4-fluoropiperidin-1-yl)phenyl)piperidine-2,6-dione (308); (R)- 3-(4-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)-3-methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,3-difluorophenyl)piperidine- 2,6-dione (309); (R)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,3- difluorophenyl)piperidine-2,6-dione (310); (R)-3-(4-(4-((4-((4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)sulfonyl)piperazin-1- yl)methyl)piperidin-1-yl)-2,3-difluorophenyl)piperidine-2,6-dione (311); (R)-3-(4-(4-((4-((4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)sulfonyl)piperidin-1-yl)methyl)piperidin-1-yl)-2,3-difluorophenyl)piperidine- 2,6-dione (312); (R)-3-(4-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,3- difluorophenyl)piperidine-2,6-dione (313); (R)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1- yl)methyl)piperidin-1-yl)-2,3-difluorophenyl)piperidine-2,6-dione (314); (R)-3-(4-(4-(((S)-4- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)- 2-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (315); (S)-1-(4-(4- ((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)-2-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine- 2,4(1H,3H)-dione (316); (R)-1-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1-yl)methyl)piperidin-1- yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (317); (R)-1-(4-(4-((4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1- yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (318); (R)-3-(4-(4- - 107 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT (((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)-3-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (319); (R)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine- 2,6-dione (320); (R)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (321); 1-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol- 4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)piperazin-1-yl)methyl)piperidin-1- yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (323); 1-(4-(4-((4-((4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)sulfonyl)piperazin-1- yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (324); 1-(4-(4-((4-((4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)sulfonyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine- 2,4(1H,3H)-dione (325); (R)-3-(4-(4-((4-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)sulfonyl)piperazin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (326); (R)-3-(4-(4-((4-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)sulfonyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (327); (S)-3-(4-(4-(((S)-4-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine- 2,6-dione (328); rac-1-[4-(4-{[(3R)-3-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-4-methylpiperazin-1-yl]methyl}piperidin-1- yl)phenyl]-1,3-diazinane-2,4-dione (329); (3R)-3-[4-(4-{[(3RS)-3-(4-{[6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-4-methylpiperazin-1- yl]methyl}piperidin-1-yl)phenyl]piperidine-2,6-dione (330); 1-[4-(4-{[4-(4-{[6-bromo-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2,2- dimethylpiperazin-1-yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3-diazinane-2,4-dione (331); 1-[4-(4-{[4-(4-{[6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl]oxy}phenyl)-2,2-dimethylpiperazin-1-yl]methyl}piperidin-1-yl)phenyl]-1,3- diazinane-2,4-dione (333); (3R)-3-[4-(4-{[4-(4-{[6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2,2-dimethylpiperazin-1-yl]methyl}piperidin-1- yl)phenyl]piperidine-2,6-dione (334); 1-[5-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol- 4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2,2-dimethylpiperidin-1- - 108 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT yl]methyl}piperidin-1-yl)pyridin-2-yl]-1,3-diazinane-2,4-dione (335); 1-[4-(4-{[4-(4-{[6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2,2- dimethylpiperidin-1-yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3-diazinane-2,4-dione (336); 1-[4-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl]oxy}phenyl)-3,3-dimethylpiperidin-1-yl]methyl}piperidin-1-yl)-3- fluorophenyl]-1,3-diazinane-2,4-dione (338); 1-[4-(4-{[(2S)-4-(4-{[6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2-methylpiperazin-1- yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3-diazinane-2,4-dione (339); 1-[4-(4-{[(3S)-4-(4- {[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}-2- fluorophenyl)-3-methylpiperazin-1-yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3-diazinane- 2,4-dione (341); rac-1-[4-(4-{[(4R)-4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-3,3-dimethylpiperidin-1-yl]methyl}piperidin-1- yl)phenyl]-1,3-diazinane-2,4-dione (346); (3R)-3-[4-(4-{[(4RS)-4-(4-{[6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2,2- dimethylpiperidin-1-yl]methyl}piperidin-1-yl)phenyl]piperidine-2,6-dione (350); rac-1-[4-(4- {[(4R)-4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl]oxy}phenyl)-2,2-dimethylpiperidin-1-yl]methyl}piperidin-1-yl)phenyl]-1,3-diazinane-2,4- dione (351); 1-[4-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl]oxy}phenyl)-2,2-dimethylpiperazin-1-yl]methyl}piperidin-1-yl)-3- fluorophenyl]-1,3-diazinane-2,4-dione (352); 1-[4-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2,2-dimethylpiperazin-1- yl]methyl}piperidin-1-yl)-2-fluorophenyl]-1,3-diazinane-2,4-dione (353); rac-(3R)-3-[2-(4- {[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl]oxy}phenyl)-2,2-dimethylpiperazin-1-yl]methyl}piperidin-1-yl)pyridin-4-yl]piperidine- 2,6-dione (354); 1-[3-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2,2-dimethylpiperazin-1-yl]methyl}piperidin-1- yl)phenyl]-1,3-diazinane-2,4-dione (355); rac-(3R)-3-[4-(4-{[4-(4-{[6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2,2- dimethylpiperazin-1-yl]methyl}piperidin-1-yl)-2,6-difluorophenyl]piperidine-2,6-dione (356); (3RS)-3-[4-(4-{[(3S)-4-(4-{[6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-3-methylpiperazin-1-yl]methyl}piperidin-1-yl)-2,6- difluorophenyl]piperidine-2,6-dione (357); (3R)-3-[4-(4-{[(3R)-4-(4-{[6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}-2,6-difluorophenyl)-3- - 109 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT methylpiperazin-1-yl]methyl}piperidin-1-yl)phenyl]piperidine-2,6-dione (358); rac-1-[4-(4- {[(3R)-4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl]oxy}-2,6-difluorophenyl)-3-methylpiperazin-1-yl]methyl}piperidin-1-yl)phenyl]-1,3- diazinane-2,4-dione (359); 1-[5-(4-{[(3R)-4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl]oxy}-2,6-difluorophenyl)-3-methylpiperazin-1- yl]methyl}piperidin-1-yl)pyridin-2-yl]-1,3-diazinane-2,4-dione (360); 1-[3-(4-{[(2R)-2-(4- {[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl]oxy}phenyl)morpholin-4-yl]methyl}piperidin-1-yl)phenyl]-1,3-diazinane-2,4-dione (361); 1-[3-(4-{[(2S)-2-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin- 7-yl]oxy}phenyl)morpholin-4-yl]methyl}piperidin-1-yl)phenyl]-1,3-diazinane-2,4-dione (362); (3R)-3-[4-(4-{[(2S)-2-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)morpholin-4-yl]methyl}piperidin-1- yl)phenyl]piperidine-2,6-dione (363); 1-[3-(4-{[(3S)-4-(4-{[6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-3-methylpiperazin-1- yl]methyl}piperidin-1-yl)phenyl]-1,3-diazinane-2,4-dione (364); (3RS)-3-[3-(4-{[(3S)-4-(4- {[6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-3- methylpiperazin-1-yl]methyl}piperidin-1-yl)phenyl]piperidine-2,6-dione (365); (3RS)-3-[2- (4-{[(3S)-4-(4-{[6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl]oxy}phenyl)-3-methylpiperazin-1-yl]methyl}piperidin-1-yl)pyridin-4-yl]piperidine-2,6- dione (366); 1-[3-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl]oxy}phenyl)piperidin-1-yl]methyl}piperidin-1-yl)phenyl]-1,3-diazinane-2,4- dione (367); 1-[4-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl]oxy}phenyl)piperidin-1-yl]methyl}piperidin-1-yl)phenyl]-1,3-diazinane-2,4- dione (368); rac-(3R)-3-[4-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)piperidin-1-yl]methyl}piperidin-1-yl)-2,6- difluorophenyl]piperidine-2,6-dione (369); 1-[4-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)piperidin-1-yl]methyl}piperidin-1- yl)-2-fluorophenyl]-1,3-diazinane-2,4-dione (370); and 1-[4-(4-{[4-(4-{[6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)piperidin-1- yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3-diazinane-2,4-dione (371).

[0246] In certain embodiments, the compound is selected from the group consisting of (R)- 1-(4-(4-((4-(5-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)-3-fluoropyridin-2-yl)-2-methylpiperazin-1-yl)methyl)piperidin-1- - 110 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (286); and (S)-1-(4-(4-((4-(5-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-3-fluoropyridin-2-yl)-2- methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (287); 1-[4-(4-{[(2S)-4-(5-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl]oxy}-3-fluoropyridin-2-yl)-2-methylpiperazin-1-yl]methyl}piperidin-1-yl)-3- fluorophenyl]-1,3-diazinane-2,4-dione (340); 1-[4-(4-{[(3S)-4-(5-{[6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}pyridin-2-yl)-3-methylpiperazin-1- yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3-diazinane-2,4-dione (343); 1-[4-(4-{[(3S)-4-(5- {[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}pyridin-2- yl)-3-methylpiperazin-1-yl]methyl}piperidin-1-yl)phenyl]-1,3-diazinane-2,4-dione (345); and (3R)-3-[4-(4-{[(3S)-4-(5-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl]oxy}pyridin-2-yl)-3-methylpiperazin-1-yl]methyl}piperidin-1- yl)phenyl]piperidine-2,6-dione (347).

[0247] In certain embodiments, the compound is selected from the group consisting of (R)- 4-((6-chloro-2-(4-(4-((1-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)piperazin- 1-yl)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-phenylbenzamide (136); (S)-4-((6- chloro-2-(4-(4-((1-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)piperazin-1- yl)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-phenylbenzamide (137); (S)-4-((6-chloro- 2-(4-(4-((1-(4-(2,6-dioxopiperidin-3-yl)-3-fluorophenyl)piperidin-4-yl)methyl)piperazin-1- yl)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-phenylbenzamide (172); and (S)-4-((6- chloro-2-(4-(4-((1-(4-(2,6-dioxopiperidin-3-yl)-2-fluorophenyl)piperidin-4- yl)methyl)piperazin-1-yl)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-phenylbenzamide (173).

[0248] In certain embodiments, the compound is selected from the group consisting of (R)- 3-(4-(4-((4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2- yl)benzyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (138); (S)-3-(3- (4-((4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2- yl)benzyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (139); (S)-3-(4- (4-((4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2- yl)benzyl)piperazin-1-yl)methyl)piperidin-1-yl)-2-fluorophenyl)piperidine-2,6-dione (170); (S)-3-(4-(4-((4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin- 2-yl)benzyl)piperazin-1-yl)methyl)piperidin-1-yl)-3-fluorophenyl)piperidine-2,6-dione (171); and (R)-3-(4-(4-((4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5- - 111 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT b]pyridin-2-yl)phenyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (245).

[0249] In certain embodiments, the compound is selected from the group consisting of (S)- 3-(6-((S)-3-(2-(4-(4-(6-bromo-7-(4-((5-methylisoxazol-3-yl)methyl)piperazin-1-yl)-3H- imidazo[4,5-b]pyridin-2-yl)phenyl)piperazin-1-yl)ethyl)pyrrolidin-1-yl)pyridin-3- yl)piperidine-2,6-dione (160); (R)-3-(4-((4-((4-(4-(6-bromo-7-(4-((5-methylisoxazol-3- yl)methyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)phenyl)piperazin-1- yl)methyl)cyclohexyl)oxy)phenyl)piperidine-2,6-dione (161); (R)-3-(4-(4-((4-(4-(6-bromo-7- (4-((5-methylisoxazol-3-yl)methyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2- yl)phenyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (162); 3-(3-(4- ((4-(4-(6-bromo-7-(4-((5-methylisoxazol-3-yl)methyl)piperazin-1-yl)-3H-imidazo[4,5- b]pyridin-2-yl)phenyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (163); (S)-4-(4-((4-(4-(6-bromo-7-(4-((5-methylisoxazol-3-yl)methyl)piperazin-1-yl)-3H- imidazo[4,5-b]pyridin-2-yl)phenyl)piperazin-1-yl)methyl)piperidin-1-yl)-N-(2,6- dioxopiperidin-3-yl)picolinamide (164); (S)-5-(4-((4-(4-(6-bromo-7-(4-((5-methylisoxazol-3- yl)methyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)phenyl)piperazin-1- yl)methyl)piperidin-1-yl)-N-(2,6-dioxopiperidin-3-yl)picolinamide (165); (S)-3-(4-((R)-3-((4- (4-(6-bromo-7-(4-((5-methylisoxazol-3-yl)methyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin- 2-yl)phenyl)piperazin-1-yl)methyl)pyrrolidin-1-yl)phenyl)piperidine-2,6-dione (166); (S)-3- (4-((S)-3-((4-(4-(6-bromo-7-(4-((5-methylisoxazol-3-yl)methyl)piperazin-1-yl)-3H- imidazo[4,5-b]pyridin-2-yl)phenyl)piperazin-1-yl)methyl)pyrrolidin-1-yl)phenyl)piperidine- 2,6-dione (167); (R)-3-(4-(4-((4-(4-(6-bromo-7-(4-((5-methylisoxazol-3-yl)methyl)piperazin- 1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)phenyl)piperazin-1-yl)methyl)piperidin-1-yl)-2- fluorophenyl)piperidine-2,6-dione (168); and (R)-3-(4-(4-((4-(4-(6-bromo-7-(4-((5- methylisoxazol-3-yl)methyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2- yl)phenyl)piperazin-1-yl)methyl)piperidin-1-yl)-3-fluorophenyl)piperidine-2,6-dione (169).

[0250] In certain embodiments, the compound is selected from the group consisting of (R)- 3-(4-(4-(2-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidin-4-yl)acetyl)piperazin-1-yl)phenyl)piperidine-2,6-dione (24); 4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4- (4-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperazine-1- carbonyl)cyclohexyl)methyl)benzamide (25); (S)-4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4- yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(4-(((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3- - 112 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT yl)piperidin-4-yl)methyl)amino)cyclohexyl)-N-methylbenzamide (26); (S)-4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-(((1-(5-(2,6- dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)amino)propyl)benzamide (27); (S)-4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((1-((1- (5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)piperidin-4- yl)methyl)benzamide (28); (S)-4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-(2-(((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3- yl)piperidin-4-yl)methyl)(methyl)amino)ethyl)benzamide (29); (S)-4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-(((1-(5-(2,6- dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)amino)-2,2- dimethylpropyl)benzamide (30); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-((1-((1-(5-((S)-2,6-dioxopiperidin-3-yl)pyridin-3- yl)piperidin-4-yl)methyl)pyrrolidin-3-yl)methyl)benzamide (31); (S)-4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(4-(((1-(5-(2,6- dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)amino)butyl)benzamide (32); (S)-4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(2-(1- ((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)piperidin-4- yl)ethyl)benzamide (33); (S)-3-(5-(4-((4-((1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidin-4-yl)methyl)piperidin-1- yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (34); (S)-3-(5-(4-((4-(4-((6-chloro- 2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazin-1- yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (35); (3S)-3-(5-(4-((4-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-3- methylpiperazin-1-yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (36); (S)-4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-(((1-(5- (2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)amino)propyl)-N- methylbenzamide (37); (S)-N-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-methylbenzamido)cyclohexyl)-1-((1-(5-(2,6- dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)piperidine-4-carboxamide (38); (S)-N- (3-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzamido)propyl)-1-((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4- yl)methyl)piperidine-4-carboxamide (39); (S)-4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((1-(1-((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3- - 113 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT yl)piperidin-4-yl)methyl)piperidine-4-carbonyl)piperidin-4-yl)methyl)benzamide (40); (S)-N- (2-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzamido)ethyl)-1-((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4- yl)methyl)-N-methylpiperidine-4-carboxamide (41); (S)-N-(3-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzamido)-2,2-dimethylpropyl)-1-((1- (5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)piperidine-4-carboxamide (42); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N- ((1-(1-((1-(5-((S)-2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)piperidine-4- carbonyl)pyrrolidin-3-yl)methyl)benzamide (43); (S)-N-(4-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzamido)butyl)-1-((1-(5-(2,6- dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)piperidine-4-carboxamide (44); (S)-N- (4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzamido)cyclohexyl)-1-((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4- yl)methyl)piperidine-4-carboxamide (45); (S)-4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(2-(1-(1-((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3- yl)piperidin-4-yl)methyl)piperidine-4-carbonyl)piperidin-4-yl)ethyl)benzamide (46); (S)-3-(5- (4-((4-(4-((1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidin-4-yl)methyl)piperidine-1-carbonyl)piperidin-1-yl)methyl)piperidin- 1-yl)pyridin-3-yl)piperidine-2,6-dione (47); (S)-3-(5-(4-((4-(4-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazine-1- carbonyl)piperidin-1-yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (48); (3S)-3- (5-(4-((4-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)-3-methylpiperazine-1-carbonyl)piperidin-1-yl)methyl)piperidin-1- yl)pyridin-3-yl)piperidine-2,6-dione (49); (S)-N-(3-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol- 4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-methylbenzamido)propyl)-1-((1-(5-(2,6- dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)piperidine-4-carboxamide (50); (S)-4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(4-(((1- (5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)amino)cyclohexyl)benzamide (51); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N- (4-(3-(((4-((S)-2,6-dioxopiperidin-3-yl)phenyl)amino)methyl)piperidine-1- carbonyl)benzyl)benzamide (52); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-(4-(5-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)benzyl)benzamide (53); (3S)-3-(4-(6- - 114 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT (1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidine-3-carbonyl)-2,6-diazaspiro[3.4]octan-2-yl)phenyl)piperidine-2,6- dione (54); (3S)-3-(4-(5-(2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)morpholin-2-yl)acetyl)hexahydropyrrolo[3,4- c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (55); 4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-(2-(4-((S)-2,6- dioxopiperidin-3-yl)phenyl)-2,6-diazaspiro[3.4]octane-6- carbonyl)cyclohexyl)methyl)benzamide (56); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-(3-(((4-((S)-2,6-dioxopiperidin-3- yl)phenyl)amino)methyl)piperidine-1-carbonyl)benzyl)benzamide (57); (3S)-3-(4-(((1-(2-(4- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)morpholin-2-yl)acetyl)piperidin-3-yl)methyl)amino)phenyl)piperidine-2,6- dione (58); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)-N-((2R)-1-(5-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)hexahydropyrrolo[3,4-c]pyrrol- 2(1H)-yl)-3-methyl-1-oxobutan-2-yl)benzamide (59); (S)-3-(4-(6-((4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-L-prolyl)-2,6- diazaspiro[3.4]octan-2-yl)phenyl)piperidine-2,6-dione (60); (S)-3-(4-(6-(2-(1-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidin-4- yl)acetyl)-2,6-diazaspiro[3.4]octan-2-yl)phenyl)piperidine-2,6-dione (61); (S)-3-(4-(6-(2-(4- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperazin-1-yl)acetyl)-2,6-diazaspiro[3.4]octan-2-yl)phenyl)piperidine-2,6- dione (62); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)-N-((2R)-1-(3-(((4-((S)-2,6-dioxopiperidin-3-yl)phenyl)amino)methyl)piperidin-1-yl)- 3-methyl-1-oxobutan-2-yl)benzamide (63); (3S)-3-(4-(5-(2-(4-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazin-1- yl)acetyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (64); 4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((R)-1-(2- (4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2,6-diazaspiro[3.4]octan-6-yl)-3-methyl-1-oxobutan- 2-yl)benzamide (65); (3S)-3-(4-(6-(2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)morpholin-2-yl)acetyl)-2,6-diazaspiro[3.4]octan-2- yl)phenyl)piperidine-2,6-dione (66); (S)-4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-(4-(2-(4-(2,6-dioxopiperidin-3-yl)phenyl)-2,6- diazaspiro[3.4]octane-6-carbonyl)benzyl)benzamide (67); (3S)-3-(4-(5-(2-(1-(4-((6-chloro-2- - 115 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidin-4- yl)acetyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (68); (S)-1-(4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N- ((1-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)-N-methylpiperidine-4- carboxamide (69); (S)-3-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzamido)methyl)-N-((1-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4- yl)methyl)-N-methylbenzamide (70); 1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)piperidin-4-yl)methyl)-N-methylpiperidine-3-carboxamide (71); (3S)-3-(4-(((1-(2- (4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperazin-1-yl)acetyl)piperidin-3-yl)methyl)amino)phenyl)piperidine-2,6- dione (72); (3S)-3-(4-(5-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)-L-prolyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)- yl)phenyl)piperidine-2,6-dione (73); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-(((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)piperidin-4-yl)methyl)(methyl)carbamoyl)cyclohexyl)methyl)benzamide (74); (S)- 1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)-N-((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)-N- methylpyrrolidine-2-carboxamide (75); (S)-2-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4- yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidin-4-yl)-N-((1-(4-(2,6-dioxopiperidin- 3-yl)phenyl)piperidin-4-yl)methyl)-N-methylacetamide (76); (3S)-3-(4-(((1-(2-(1-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidin-4-yl)acetyl)piperidin-3-yl)methyl)amino)phenyl)piperidine-2,6- dione (77); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)-N-(((1S,4r)-4-(5-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)octahydropyrrolo[3,4- c]pyrrole-2-carbonyl)cyclohexyl)methyl)benzamide (78); (S)-2-(4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazin-1-yl)-N- ((1-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)-N-methylacetamide (79); 4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((R)-1- (((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)(methyl)amino)-3-methyl- 1-oxobutan-2-yl)benzamide (80); 2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)morpholin-2-yl)-N-((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)piperidin-4-yl)methyl)-N-methylacetamide (81); (3S)-3-(4-(5-(1-(4-((6-chloro-2- - 116 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-3- carbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (82); (S)-4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-(2-(4- (2,6-dioxopiperidin-3-yl)phenyl)-2,6-diazaspiro[3.4]octane-6-carbonyl)benzyl)benzamide (83); (S)-4-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzamido)methyl)-N-((1-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)- N-methylbenzamide (84); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)-N-(3-(5-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)octahydropyrrolo[3,4- c]pyrrole-2-carbonyl)benzyl)benzamide (85); (S)-3-(4-(6-(1-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4-carbonyl)-2,6- diazaspiro[3.4]octan-2-yl)phenyl)piperidine-2,6-dione (86); (3S)-3-(4-(5-(1-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4- carbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (87); (S)-1-(4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N- (1-(4-(2,6-dioxopiperidin-3-yl)phenyl)-4-methylpiperidin-4-yl)piperidine-4-carboxamide (88); (S)-3-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzamido)methyl)-N-(1-(4-(2,6-dioxopiperidin-3-yl)phenyl)-4-methylpiperidin-4- yl)benzamide (89); 1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)-N-(1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-4-methylpiperidin- 4-yl)piperidine-3-carboxamide (90); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-4- methylpiperidin-4-yl)carbamoyl)cyclohexyl)methyl)benzamide (91); (S)-1-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-(1-(4-((S)- 2,6-dioxopiperidin-3-yl)phenyl)-4-methylpiperidin-4-yl)pyrrolidine-2-carboxamide (92); (S)- 2-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidin-4-yl)-N-(1-(4-(2,6-dioxopiperidin-3-yl)phenyl)-4-methylpiperidin- 4-yl)acetamide (93); (S)-2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazin-1-yl)-N-(1-(4-(2,6-dioxopiperidin-3- yl)phenyl)-4-methylpiperidin-4-yl)acetamide (94); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol- 4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((R)-1-((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)-4-methylpiperidin-4-yl)amino)-3-methyl-1-oxobutan-2-yl)benzamide (95); 4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((S)-1-((1- (4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-4-methylpiperidin-4-yl)amino)-1-oxopropan-2-yl)-N- - 117 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT methylbenzamide (96); 2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)morpholin-2-yl)-N-(1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-4- methylpiperidin-4-yl)acetamide (97); (S)-4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-(1-((1-(4-(2,6-dioxopiperidin-3-yl)phenyl)-4- methylpiperidin-4-yl)amino)-2-methyl-1-oxopropan-2-yl)benzamide (98); (S)-4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(4-((1-(4-(2,6- dioxopiperidin-3-yl)phenyl)-4-methylpiperidin-4-yl)carbamoyl)benzyl)benzamide (99); 3-((4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzamido)methyl)-N-((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)pyrrolidin-3- yl)methyl)-N-methylbenzamide (100); 1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)pyrrolidin-3-yl)methyl)-N-methylpiperidine-3-carboxamide (101); 4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-(((1-(4- ((S)-2,6-dioxopiperidin-3-yl)phenyl)pyrrolidin-3- yl)methyl)(methyl)carbamoyl)cyclohexyl)methyl)benzamide (102); (2S)-1-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-((1-(4-((S)- 2,6-dioxopiperidin-3-yl)phenyl)pyrrolidin-3-yl)methyl)-N-methylpyrrolidine-2-carboxamide (103); 2-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidin-4-yl)-N-((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)pyrrolidin-3- yl)methyl)-N-methylacetamide (104); 2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazin-1-yl)-N-((1-(4-((S)-2,6- dioxopiperidin-3-yl)phenyl)pyrrolidin-3-yl)methyl)-N-methylacetamide (105); 4-((6-chloro- 2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((2R)-1-(((1-(4- ((S)-2,6-dioxopiperidin-3-yl)phenyl)pyrrolidin-3-yl)methyl)(methyl)amino)-3-methyl-1- oxobutan-2-yl)benzamide (106); 2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)morpholin-2-yl)-N-((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)pyrrolidin-3-yl)methyl)-N-methylacetamide (107); 4-((4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzamido)methyl)-N-((1-(4- ((S)-2,6-dioxopiperidin-3-yl)phenyl)pyrrolidin-3-yl)methyl)-N-methylbenzamide (108); 4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-((R)- 4-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2-methylpiperazine-1-carbonyl)benzyl)benzamide (109); (S)-3-(4-((R)-4-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)piperidine-4-carbonyl)-3-methylpiperazin-1- - 118 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT yl)phenyl)piperidine-2,6-dione (110); (3S)-3-(4-((3R)-4-(1-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-3-carbonyl)-3- methylpiperazin-1-yl)phenyl)piperidine-2,6-dione (111); 4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1R,4r)-4-((R)-4-(4-((S)-2,6- dioxopiperidin-3-yl)phenyl)-2-methylpiperazine-1-carbonyl)cyclohexyl)methyl)benzamide (112); (S)-3-(4-((R)-4-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)-L-prolyl)-3-methylpiperazin-1-yl)phenyl)piperidine-2,6-dione (113); (S)-3-(4-((R)-4-(2-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)piperidin-4-yl)acetyl)-3-methylpiperazin-1-yl)phenyl)piperidine- 2,6-dione (114); (S)-3-(4-((R)-4-(2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazin-1-yl)acetyl)-3-methylpiperazin-1- yl)phenyl)piperidine-2,6-dione (115); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-((R)-1-((R)-4-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2- methylpiperazin-1-yl)-3-methyl-1-oxobutan-2-yl)benzamide (116); (3S)-3-(4-((3R)-4-(2-(4- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)morpholin-2-yl)acetyl)-3-methylpiperazin-1-yl)phenyl)piperidine-2,6-dione (117); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N- (4-((R)-4-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2-methylpiperazine-1- carbonyl)benzyl)benzamide (118); (S)-3-(4-(4-((1-(1-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4-carbonyl)piperidin-4- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (119); (S)-4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-(4-((1-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperidin-4-yl)methyl)piperidine-1-carbonyl)benzyl)benzamide (120); (3S)-3-(4-(4- ((1-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidine-3-carbonyl)piperidin-4-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (121); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1r,4r)-4-(4-((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)piperidin-4-yl)methyl)piperidine-1-carbonyl)cyclohexyl)methyl)benzamide (122); (S)-3-(4-(4-((1-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)-L-prolyl)piperidin-4-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (123); (S)-3-(4-(4-((1-(2-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)piperidin-4-yl)acetyl)piperidin-4-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (124); (S)-3-(4-(4-((1-(2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H- - 119 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazin-1-yl)acetyl)piperidin-4- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (125); 4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((R)-1-(4-((1-(4-((S)-2,6- dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)piperidin-1-yl)-3-methyl-1-oxobutan-2- yl)benzamide (126); (3S)-3-(4-(4-((1-(2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)morpholin-2-yl)acetyl)piperidin-4- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (127); (S)-4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(4-(4-((1-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperidin-4-yl)methyl)piperidine-1-carbonyl)benzyl)benzamide (128); (3S)-3-(4- (((1-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidine-3-carbonyl)piperidin-3-yl)methyl)amino)phenyl)piperidine-2,6- dione (129); (3S)-3-(4-(((1-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)-L-prolyl)piperidin-3-yl)methyl)amino)phenyl)piperidine-2,6- dione (130); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)-N-(((1S,4r)-4-(3-(((4-((S)-2,6-dioxopiperidin-3-yl)phenyl)amino)methyl)piperidine- 1-carbonyl)cyclohexyl)methyl)benzamide (131); 1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol- 4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-((1-(4-((R)-2,6-dioxopiperidin-3- yl)phenyl)pyrrolidin-3-yl)methyl)-N-methylpiperidine-4-carboxamide (132); (S)-3-(5-(4- (((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)-3-methylpiperazin-1-yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6- dione (133); (S)-3-(5-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-3-methylpiperazin-1-yl)methyl)piperidin-1- yl)pyridin-3-yl)piperidine-2,6-dione (134); (S)-3-(3-(4-((4-((1-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)piperidin-4- yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (142); (S)-3-(3- (4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)-2-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (144); (S)-3-(3-(4-((4-((1-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)piperidin-4-yl)methyl)piperidin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (146); (S)-3-(3-(4-((4-(4-((6-bromo-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (147); (S)-3-(3-(4-(((R)-4-(4-((6-bromo-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-2-methylpiperazin-1- - 120 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (148); (S)-3-(3-(4-((4-(4-(4-((6-chloro- 2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)piperidine-1- carbonyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (150); (R)-3-(4-(4- ((4-((1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)piperidin-4-yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine- 2,6-dione (151); (R)-3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)piperazin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (152); (R)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2-methylpiperazin-1- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (153); (R)-3-(4-(4-((4-((1-(4-((6-bromo- 2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidin-4- yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (155); (R)-3-(4- (4-((4-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (156); (R)- 3-(4-(4-(((R)-4-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)-2-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (157); (R)-3-(4-(4-((4-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)phenyl)piperidine-1-carbonyl)piperidin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (159); (S)-3-(3-((R)-4-(1-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4-carbonyl)-3- methylpiperazin-1-yl)phenyl)piperidine-2,6-dione (181); 4-((6-bromo-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1R,4r)-4-((R)-4-(3-((S)-2,6- dioxopiperidin-3-yl)phenyl)-2-methylpiperazine-1-carbonyl)cyclohexyl)methyl)benzamide (182); (3S)-3-(4-(4-(4-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)-1-methylpiperazine-2-carbonyl)piperazin-1- yl)phenyl)piperidine-2,6-dione (188); (3S)-3-(4-(4-(4-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-1-methylpiperazine-2- carbonyl)piperazin-1-yl)phenyl)piperidine-2,6-dione (189); (3S)-3-(4-(7-(4-(4-((6-bromo-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-1- methylpiperazine-2-carbonyl)-2,7-diazaspiro[4.5]decan-2-yl)phenyl)piperidine-2,6-dione (206); (3S)-3-(4-(5-(4-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)-1-methylpiperazine-2-carbonyl)hexahydropyrrolo[3,4-c]pyrrol- 2(1H)-yl)phenyl)piperidine-2,6-dione (214); 4-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4- - 121 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-(1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)-4-methylpiperidin-4-yl)-1-methylpiperazine-2-carboxamide (226); 2-((R)-1-(4-((6- bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)pyrrolidin-3-yl)-N-((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)pyrrolidin-3- yl)methyl)-N-methylacetamide (227); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-((1S,4r)-4-(((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)pyrrolidin-3-yl)methyl)(methyl)carbamoyl)cyclohexyl)benzamide (228); (S)-3-(4- ((R)-4-(1-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidine-4-carbonyl)-3-methylpiperazin-1-yl)phenyl)piperidine-2,6-dione (229); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N- (3-((R)-4-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2-methylpiperazin-1-yl)-3- oxopropyl)benzamide (230); 4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)-N-(2-((R)-4-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2-methylpiperazin- 1-yl)-2-oxoethyl)-N-methylbenzamide (231); (3S)-3-(4-((3R)-4-(4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-1-methylpiperazine- 2-carbonyl)-3-methylpiperazin-1-yl)phenyl)piperidine-2,6-dione (232); (S)-1-(4-((6-bromo-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-((1-(4-(2,6- dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)-N-methylpiperidine-4-carboxamide (233); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N- ((1S,4r)-4-(((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-4- yl)methyl)(methyl)carbamoyl)cyclohexyl)benzamide (234); (R)-3-(4-(4-((4-(2-(1-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidin-4-yl)ethyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine- 2,6-dione (247); (R)-3-(4-(4-((4-((1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidin-4-yl)methoxy)piperidin-1- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (248); (R)-3-(4-(4-((4-((1-(4-((6-chloro- 2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidin-4- yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (249); (R)-3-(5- (4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)-2-methylpiperazin-1-yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6- dione (250); (R)-3-(5-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-3-methylpiperazin-1-yl)methyl)piperidin-1- yl)pyridin-3-yl)piperidine-2,6-dione (251); (R)-3-(5-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl- - 122 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2-(hydroxymethyl)piperazin-1- yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (252); (3R)-3-(5-(4-((3-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-3,6- diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (253); (R)-3-(5-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzyl)-2-methylpiperazin-1-yl)methyl)piperidin-1-yl)pyridin-3- yl)piperidine-2,6-dione (254); (R)-3-(5-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol- 4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2-(hydroxymethyl)piperazin-1- yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (255); (R)-3-(5-(4-(((S)-4-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-3- methylpiperazin-1-yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (256); (R)-3-(3- (4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)-2-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (257); (R)-3-(3-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzyl)-3-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine- 2,6-dione (258); (R)-3-(3-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2-(hydroxymethyl)piperazin-1-yl)methyl)piperidin- 1-yl)phenyl)piperidine-2,6-dione (259); (3R)-3-(3-(4-((3-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-3,6-diazabicyclo[3.1.1]heptan-6- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (260); (R)-3-(3-(4-(((R)-4-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2- (hydroxymethyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (261); (R)- 3-(3-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)-3-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (262); (R)-1-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzyl)-2-(hydroxymethyl)piperazin-1-yl)methyl)piperidin-1- yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (268); (R)-3-(4-(4-(((S)-4-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2- (hydroxymethyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (269); (R)- 3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)-2-(hydroxymethyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine- 2,6-dione (270); (S)-1-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2-(hydroxymethyl)piperazin-1-yl)methyl)piperidin- - 123 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT 1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (271); 3-(4-(4-((4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-3- (fluoromethyl)piperazin-1-yl)methyl)piperidin-1-yl)-2-fluorophenyl)piperidine-2,6-dione (273); 3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin- 7-yl)oxy)benzyl)-3-(fluoromethyl)piperazin-1-yl)methyl)piperidin-1-yl)-3- fluorophenyl)piperidine-2,6-dione (274); (3S)-3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2-(fluoromethyl)piperazin-1- yl)methyl)piperidin-1-yl)-2-fluorophenyl)piperidine-2,6-dione (275); (3R)-3-(4-(4-((4-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2- (fluoromethyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (276); (3S)- 3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)-3-(fluoromethyl)piperazin-1-yl)methyl)piperidin-1-yl)-3- fluorophenyl)piperidine-2,6-dione (277); (3S)-3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)-2-(fluoromethyl)piperazin-1-yl)methyl)piperidin-1-yl)-3- fluorophenyl)piperidine-2,6-dione (278); and (R)-3-(4-(4-((4-(4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)piperazine-1- carbonyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (322).

[0251] In certain embodiments, the compound is selected from the group consisting of 4- ((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N- (((1S,4r)-4-(4-(3-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperazine-1- carbonyl)cyclohexyl)methyl)benzamide (174); (3S)-3-(3-(((1-(1-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4- carbonyl)piperidin-3-yl)methyl)amino)phenyl)piperidine-2,6-dione (175); 4-((6-bromo-2- (1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-(3-(((3- ((S)-2,6-dioxopiperidin-3-yl)phenyl)amino)methyl)piperidine-1- carbonyl)cyclohexyl)methyl)benzamide (176); (3S)-3-(3-(5-(1-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4- carbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (177); 4-((6- bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4- (5-(3-((S)-2,6-dioxopiperidin-3-yl)phenyl)octahydropyrrolo[3,4-c]pyrrole-2- carbonyl)cyclohexyl)methyl)benzamide (178); (S)-3-(3-(6-(1-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4-carbonyl)-2,6- - 124 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT diazaspiro[3.4]octan-2-yl)phenyl)piperidine-2,6-dione (179); 4-((6-bromo-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-(2-(3-((S)-2,6- dioxopiperidin-3-yl)phenyl)-2,6-diazaspiro[3.4]octane-6- carbonyl)cyclohexyl)methyl)benzamide (180); (S)-3-(4-(4-(1-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4- carbonyl)piperazin-1-yl)phenyl)piperidine-2,6-dione (183); 4-((6-bromo-2-(1,3-dimethyl-1H- pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-(4-(4-((S)-2,6- dioxopiperidin-3-yl)phenyl)piperazine-1-carbonyl)cyclohexyl)methyl)benzamide (184); (S)- 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(2-(4- (4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-1-yl)-2-oxoethyl)benzamide (185); (S)-4-((6- bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-(4-(4- (2,6-dioxopiperidin-3-yl)phenyl)piperazin-1-yl)-3-oxopropyl)benzamide (186); (3S)-3-(4-(4- (3-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)pyrrolidin-3-yl)propanoyl)piperazin-1-yl)phenyl)piperidine-2,6-dione (187); (3S)-3-(4-(((1-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin- 7-yl)oxy)benzoyl)piperidine-4-carbonyl)piperidin-3-yl)methyl)amino)phenyl)piperidine-2,6- dione (190); 4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)-N-(((1S,4r)-4-(3-(((4-((S)-2,6-dioxopiperidin-3-yl)phenyl)amino)methyl)piperidine- 1-carbonyl)cyclohexyl)methyl)benzamide (191); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4- yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(2-(3-(((4-((S)-2,6-dioxopiperidin-3- yl)phenyl)amino)methyl)piperidin-1-yl)-2-oxoethyl)benzamide (192); 1-(4-((6-bromo-2-(1,3- dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-(1-(4-((S)-2,6- dioxopiperidin-3-yl)phenyl)piperidin-3-yl)piperidine-4-carboxamide (193); 4-((6-bromo-2- (1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-((1-(4- ((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-3-yl)carbamoyl)cyclohexyl)methyl)benzamide (194); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N- (2-((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-3-yl)amino)-2-oxoethyl)benzamide (195); 4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N- (3-((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-3-yl)amino)-3-oxopropyl)benzamide (196); 5-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)-N-(1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-3-yl)-5- azaspiro[2.3]hexane-1-carboxamide (197); 2-((R)-1-(4-((6-bromo-2-(1,3-dimethyl-1H- pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)pyrrolidin-3-yl)-N-(1-(4-((S)-2,6- - 125 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT dioxopiperidin-3-yl)phenyl)piperidin-3-yl)acetamide (198); 5-(4-((6-bromo-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-(1-(4-((S)-2,6- dioxopiperidin-3-yl)phenyl)piperidin-3-yl)-5-azaspiro[2.3]hexane-1-carboxamide (199); 4- ((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((1S,4r)- 4-((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-3- yl)carbamoyl)cyclohexyl)benzamide (200); (3S)-3-(4-(7-(1-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4-carbonyl)-2,7- diazaspiro[4.5]decan-2-yl)phenyl)piperidine-2,6-dione (201); 4-((6-bromo-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-(2-(4-((S)-2,6- dioxopiperidin-3-yl)phenyl)-2,7-diazaspiro[4.5]decane-7- carbonyl)cyclohexyl)methyl)benzamide (202); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4- yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(2-(2-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2,7- diazaspiro[4.5]decan-7-yl)-2-oxoethyl)benzamide (203); 4-((6-bromo-2-(1,3-dimethyl-1H- pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-(2-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)-2,7-diazaspiro[4.5]decan-7-yl)-3-oxopropyl)benzamide (204); (3S)-3-(4-(7-(3-(1- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)pyrrolidin-3-yl)propanoyl)-2,7-diazaspiro[4.5]decan-2-yl)phenyl)piperidine- 2,6-dione (205); (3S)-3-(4-(7-(2-((R)-1-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)pyrrolidin-3-yl)acetyl)-2,7-diazaspiro[4.5]decan-2- yl)phenyl)piperidine-2,6-dione (207); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-((1S,4r)-4-(2-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2,7- diazaspiro[4.5]decane-7-carbonyl)cyclohexyl)benzamide (208); (3S)-3-(4-(7-(2-((R)-1-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)pyrrolidin-3-yl)acetyl)-2,7-diazaspiro[4.5]decan-2-yl)phenyl)piperidine-2,6- dione (209); 4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)-N-((1S,4r)-4-(2-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2,7-diazaspiro[4.5]decane-7- carbonyl)cyclohexyl)benzamide (210); (3S)-3-(4-(5-(1-(4-((6-bromo-2-(1,3-dimethyl-1H- pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4- carbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (211); 4-((6- bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4- (5-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)octahydropyrrolo[3,4-c]pyrrole-2- carbonyl)cyclohexyl)methyl)benzamide (212); (3S)-3-(4-(5-(3-(1-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)pyrrolidin-3- - 126 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT yl)propanoyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (213); 4- ((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N- (((1S,4r)-4-(2-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2,6-diazaspiro[3.4]octane-6- carbonyl)cyclohexyl)methyl)benzamide (215); (S)-3-(4-(6-(2-((R)-1-(4-((6-bromo-2-(1,3- dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)pyrrolidin-3- yl)acetyl)-2,6-diazaspiro[3.4]octan-2-yl)phenyl)piperidine-2,6-dione (216); (S)-4-((6-bromo- 2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-(6-(4-(2,6- dioxopiperidin-3-yl)phenyl)-2,6-diazaspiro[3.3]heptan-2-yl)-3-oxopropyl)benzamide (217); (3S)-3-(4-(6-(3-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin- 7-yl)oxy)benzoyl)pyrrolidin-3-yl)propanoyl)-2,6-diazaspiro[3.3]heptan-2- yl)phenyl)piperidine-2,6-dione (218); (S)-3-(4-(6-(2-((R)-1-(4-((6-bromo-2-(1,3-dimethyl-1H- pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)pyrrolidin-3-yl)acetyl)-2,6- diazaspiro[3.3]heptan-2-yl)phenyl)piperidine-2,6-dione (219); (S)-3-(4-(6-(2-((R)-1-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)pyrrolidin-3-yl)acetyl)-2,6-diazaspiro[3.3]heptan-2-yl)phenyl)piperidine-2,6- dione (220); 4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)-N-((1S,4r)-4-(6-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2,6-diazaspiro[3.3]heptane- 2-carbonyl)cyclohexyl)benzamide (221); (S)-1-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4- yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-(1-(4-(2,6-dioxopiperidin-3-yl)phenyl)-4- methylpiperidin-4-yl)piperidine-4-carboxamide (222); (S)-4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(2-((1-(4-(2,6-dioxopiperidin-3- yl)phenyl)-4-methylpiperidin-4-yl)amino)-2-oxoethyl)benzamide (223); (S)-4-((6-bromo-2- (1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-((1-(4-(2,6- dioxopiperidin-3-yl)phenyl)-4-methylpiperidin-4-yl)amino)-3-oxopropyl)benzamide (224); 3- (1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)pyrrolidin-3-yl)-N-(1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-4- methylpiperidin-4-yl)propanamide (225); (S)-3-(4-(4-((1-(1-(4-((6-bromo-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4- carbonyl)piperidin-4-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (235); and 4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((1r,4r)-4- (4-((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)piperidine-1- carbonyl)cyclohexyl)benzamide (236). - 127 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0252] In certain embodiments, the compound is selected from the group consisting of (S)- 4-((6-chloro-2-(4-(4-(1-((1-(3-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4- yl)methyl)piperidine-4-carbonyl)piperazin-1-yl)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)- N-phenylbenzamide (145); and (R)-4-((6-chloro-2-(4-(4-(1-((1-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperidin-4-yl)methyl)piperidine-4-carbonyl)piperazin-1-yl)phenyl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-phenylbenzamide (154).

[0253] In certain embodiments, the compound is selected from the group consisting of (S)- 3-(3-(4-((4-(4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin- 2-yl)benzyl)piperazine-1-carbonyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine- 2,6-dione (149); (R)-3-(4-(4-((4-(4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H- imidazo[4,5-b]pyridin-2-yl)benzyl)piperazine-1-carbonyl)piperidin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (158); (S)-3-(4-(4-((4-((4-(4-(6-bromo-7-(4-(4- chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)benzyl)piperazin-1- yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)-2-fluorophenyl)piperidine-2,6-dione (237); (3S)-3-(4-(4-((3-((4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5- b]pyridin-2-yl)benzyl)piperazin-1-yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)-2- fluorophenyl)piperidine-2,6-dione (238); (S)-3-(4-(4-((4-((4-(4-(6-bromo-7-(4-(4- chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)benzyl)piperazin-1- yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)-3-fluorophenyl)piperidine-2,6-dione (239); (3S)-3-(4-(4-((3-((4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5- b]pyridin-2-yl)benzyl)piperazin-1-yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)-3- fluorophenyl)piperidine-2,6-dione (240); (R)-3-(4-(4-((4-((4-(4-(6-bromo-7-(4-(4- chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)benzyl)piperazin-1- yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (241); (3R)-3-(4- (4-((3-((4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2- yl)benzyl)piperazin-1-yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6- dione (242); (R)-3-(4-(4-((4-(4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H- imidazo[4,5-b]pyridin-2-yl)phenyl)piperidine-1-carbonyl)piperidin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (243); and (R)-3-(4-(4-((4-((4-(4-(6-bromo-7-(4-(4- chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)phenyl)piperidin-1- yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (244).

[0254] In certain embodiments, the compound is selected from the group consisting of 1- [5-(4-{[(3S)-4-(6-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- - 128 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT yl]oxy}pyridazin-3-yl)-3-methylpiperazin-1-yl]methyl}piperidin-1-yl)pyridin-2-yl]-1,3- diazinane-2,4-dione (22) and 1-[4-(4-{[(3S)-4-(6-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4- yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}pyridazin-3-yl)-3-methylpiperazin-1- yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3-diazinane-2,4-dione (337).

[0255] In certain embodiments, the compound is selected from the group consisting of 1- (5-{4-[(7-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}- 2,3,4,5-tetrahydro-1H-3-benzazepin-3-yl)methyl]piperidin-1-yl}pyridin-2-yl)-1,3-diazinane- 2,4-dione (332) and 1-(4-{4-[(7-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl]oxy}-2,3,4,5-tetrahydro-1H-3-benzazepin-3-yl)methyl]piperidin- 1-yl}-3-fluorophenyl)-1,3-diazinane-2,4-dione (342).

[0256] In certain embodiments, the compound is selected from the group consisting of 1- [4-(4-{[(3S)-4-(5-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl]oxy}pyrimidin-2-yl)-3-methylpiperazin-1-yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3- diazinane-2,4-dione (344); 1-[4-(4-{[(3S)-4-(5-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl]oxy}pyrimidin-2-yl)-3-methylpiperazin-1- yl]methyl}piperidin-1-yl)phenyl]-1,3-diazinane-2,4-dione (348); and (3R)-3-[4-(4-{[(3S)-4- (5-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl]oxy}pyrimidin-2-yl)-3-methylpiperazin-1-yl]methyl}piperidin-1-yl)phenyl]piperidine-2,6- dione (349).

[0257] In certain embodiments of formulaa pharmaceutically acceptable salt thereof or stereoisomer thereof, R1is a substituted aryl wherein one or more substituents are independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen; and acyl. - 129 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0258] In certain embodiments of formulapharmaceutically acceptable salt thereof or stereoisomer thereof,is an unsubstituted or substituted heteroaryl wherein one or more substituents are independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen, acyl, amino, -CN, hydroxyl, nitro, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen or alkyl. In certain embodiments,is an unsubstituted heteroaryl. In certain embodiments,is a substituted heteroaryl wherein one or more substituents are independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen, acyl, amino, -CN, hydroxyl, nitro, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen or alkyl. In certain embodiments,.

[0259] In certain embodiments of formulaa pharmaceutically acceptable salt thereof or stereoisomer thereof, L is a bond. In certain embodiments,each R6is independently hydrogen, alkyl, or hydroxyl; X2is -CH2-, oxygen, -NR7-, or sulfur; R7is hydrogen or alkyl; and each n1, n2, and n3 are independently one, two, or three. - 130 - 1104745337\13\AMERICASAttorney Docket No.: 121843.00323 NU-3800 PCT

[0260] In certain embodiments, in combination with certain embodiments described in the paragraphs above, L is. In certain embodiments, n2 and n3 are one. In certain embodiments, n2 and n3 are two. In certain embodiments, n2 and n3 are three. In certain embodiments, n2 is one and n3 is two. In certain embodiments, n2 is one and n3 is three. In certain embodiments, n2 is two and n3 is three. Alternatively stated, in certain embodiments, the ring containing the nitrogen is a four-membered ring; a five-membered ring; a six- m...

Claims

Attorney Docket No.121843.00323 NU-3800 PCT WHAT IS CLAIMED IS:

1. A compound represented by Formula Ior a pharmaceutically acceptable salt thereof or stereoisomer thereof, wherein X1is halogen;Y2is an unsubstituted or substituted 5- or 6-membered aryl or heteroaryl wherein one or more substituents are independently selected from alkyl or halogen; R1is, independently, hydrogen or halogen; R3is hydrogen or alkyl; X2is -N(H)-, oxygen, or sulfur; X3is alkylene; heteroalkylene; cycloalkylene; arylene; heteroarylene; unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, haloalkyl, halogen, acyl, amino, -CN, hydroxyl, nitro, -C(O)-, -SO2-, hydroxyalkyl, alkoxyalkyl, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen, alkyl, or alkenyl; unsubstituted or substituted -S(O)2-heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen, acyl, amino, -CN, hydroxyl, nitro, hydroxyalkyl, -C(O)-, alkoxyalkyl, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, 518 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT independently, hydrogen, alkyl, or alkenyl;; ; -C(O)-; -C(O)N(H)-; -N(H)-; -O-; or -S(O)2-; X4is carbon or nitrogen, wherein when X4is nitrogen then the R1bound to X4is absent; Z1and Z2are independently carbon, nitrogen, -N(H)-, oxygen, or sulfur wherein the ring containing Z1and Z2is aromatic; Z3is an unsubstituted or substituted 5- or 6-membered aryl or heteroaryl wherein one or more substituents are independently selected from alkyl or halogen; or;L is a bond or a linker;is a ubiquitin ligase targeting moiety (UTM) having the following chemical formulawherein X5is carbon or nitrogen; R4is absent, -N(R4a)-, oxygen, sulfur, or -N(R4a)C(O)- wherein R4ais hydrogen or alkyl; R5is unsubstituted or substituted arylene or heteroarylene wherein one or more substituents are independently selected from the group consisting of halogen and alkyl; R6is absent, -N(R6a)-, oxygen, or sulfur wherein R6ais hydrogen or alkyl; 519 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT R7is absent; unsubstituted or substituted cycloalkylene or heterocycloalkylene wherein one or more substituents are independently selected from the group consisting of halogen and alkyl; an unsubstituted or substituted five- to fifteen-membered spiro heterocycloalkylene; or an unsubstituted or substituted four- to fourteen-membered fused heterocycloalkylene; R8is absent, alkylene, -C(O)-, -N(R8a)-, oxygen, or sulfur wherein R8ais hydrogen or alkyl; and each n is independently zero, one, or two.

2. The compound of claim 1, represented by Formula Ior a pharmaceutically acceptable salt thereof or stereoisomer thereof, wherein X1is halogen;Y2is an unsubstituted or substituted 5- or 6-membered aryl or heteroaryl wherein one or more substituents are independently selected from alkyl or halogen; R1is, independently, hydrogen or halogen; R3is hydrogen or alkyl; X2is -N(H)-, oxygen, or sulfur; X3is alkylene; heteroalkylene; cycloalkylene; arylene; heteroarylene; unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, haloalkyl, halogen, acyl, amino, -CN, hydroxyl, nitro, -C(O)-, -SO2-, hydroxyalkyl, alkoxyalkyl, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen, alkyl, or alkenyl; unsubstituted or substituted -S(O)2-heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, 520 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT aryl, arylalkyl, heteroaryl, halogen, acyl, amino, -CN, hydroxyl, nitro, hydroxyalkyl, -C(O)-, alkoxyalkyl, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen, alkyl, or alkenyl;; ; -C(O)-; -C(O)N(H)-; -N(H)-; -O-; or -S(O)2-; X4is carbon or nitrogen, wherein when X4is nitrogen then the R1bound to X4is absent; Z1and Z2are independently carbon, nitrogen, -N(H)-, oxygen, or sulfur wherein the ring containing Z1and Z2is aromatic; Z3is an unsubstituted or substituted 5- or 6-membered aryl or heteroaryl wherein one or more substituents are independently selected from alkyl or halogen; or; R2is selected froma linker;quitin ligase targeting moiety (UTM) having the following chemical formulawherein X5is carbon or nitrogen; R4is absent, -N(R4a)-, oxygen, sulfur, or -N(R4a)C(O)- wherein R4ais hydrogen or alkyl; 521 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT R5is unsubstituted or substituted arylene or heteroarylene wherein one or more substituents are independently selected from the group consisting of halogen and alkyl; R6is absent, -N(R6a)-, oxygen, or sulfur wherein R6ais hydrogen or alkyl; R7is absent; unsubstituted or substituted cycloalkylene or heterocycloalkylene wherein one or more substituents are independently selected from the group consisting of halogen and alkyl; an unsubstituted or substituted five- to fifteen-membered spiro heterocycloalkylene; or an unsubstituted or substituted four- to fourteen-membered fused heterocycloalkylene; and R8is absent, alkylene, -C(O)-, -N(R8a)-, oxygen, or sulfur wherein R8ais hydrogen or alkyl.

3. The compound of claim 1 or 2, represented by Formula A, B, C, D, E, F, G, or H522 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCTa pharmaceutically acceptable salt thereof or stereoisomer thereof, wherein R1is, independently, hydrogen or halogen;R3is hydrogen or alkyl; X1is halogen; X2is -N(H)-, oxygen, or sulfur; X3is alkylene; heteroalkylene; cycloalkylene; arylene; heteroarylene; unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, haloalkyl, halogen, acyl, amino, -CN, hydroxyl, nitro, -C(O)-, -SO2-, hydroxyalkyl, alkoxyalkyl, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen, alkyl, or alkenyl; unsubstituted or substituted -S(O)2-heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen, acyl, amino, -CN, hydroxyl, nitro, hydroxyalkyl, -C(O)-, 523 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT alkoxyalkyl, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen, alkyl, or alkenyl;; ; -C(O)-; -C(O)N(H)-; -N(H)-; -O-; or -S(O)2-; X4is carbon or nitrogen, wherein when X4is nitrogen then the R1bound to X4is absent; L is a bond or a linker;is a ubiquitin ligase targeting moiety (UTM) having the following chemical formulawherein X5is carbon or nitrogen; R4is absent, -N(R4a)-, oxygen, sulfur, or -N(R4a)C(O)- wherein R4ais hydrogen or alkyl; R5is unsubstituted or substituted arylene or heteroarylene wherein one or more substituents are independently selected from the group consisting of halogen and alkyl; R6is absent, -N(R6a)-, oxygen, or sulfur wherein R6ais hydrogen or alkyl; R7is absent; unsubstituted or substituted cycloalkylene or heterocycloalkylene wherein one or more substituents are independently selected from the group consisting of halogen and alkyl; an unsubstituted or substituted five- to fifteen-membered spiro heterocycloalkylene; or an unsubstituted or substituted four- to fourteen-membered fused heterocycloalkylene; R8is absent, alkylene, -C(O)-, -N(R8a)-, oxygen, or sulfur wherein R8ais hydrogen or alkyl; and each n is independently zero, one, or two.

4. The compound of claim 3, wherein the compound is represented by Formula A 524 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCTFormula A further wherein R1is, independently, hydrogen, bromo, chloro, fluoro, or iodo; X1is bromo, chloro, fluoro, or iodo; X2is oxygen; X3is alkylene; -C(O)-;; ; or unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, haloalkyl, halogen, -C(O)-, or -SO2-; and X4is carbon.

5. The compound of claim 3, wherein the compound is represented by Formula AFormula A further wherein R1is hydrogen, bromo, chloro, fluoro, or iodo; X1is bromo, chloro, fluoro, or iodo; X2is oxygen; X3is alkylene; -C(O)-;; ; or unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, haloalkyl, halogen, -C(O)-, or -SO2-; and X4is nitrogen wherein the R1bound to X4is absent. 525 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT 6. The compound of claim 3, wherein the compound is represented by Formula BFormula B further wherein R1is, independently, hydrogen, bromo, chloro, fluoro, or iodo; X1is bromo, chloro, fluoro, or iodo; X2is oxygen; X3is alkylene; -C(O)-;; ; or unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, haloalkyl, halogen, -C(O)-, or -SO2-; and X4is carbon.

7. The compound of claim 3, wherein the compound is represented by Formula Cfurther whereinR3is hydrogen, methyl, or ethyl; X1is bromo, chloro, fluoro, or iodo; and X2is oxygen.

8. The compound of claim 3, wherein the compound is represented by Formula D 526 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCTfurther whereinX1is bromo, chloro, fluoro, or iodo.

9. The compound of claim 3, wherein the compound is represented by Formula Efurther whereinX1is bromo, chloro, fluoro, or iodo.

10. The compound of claim 3, wherein the compound is represented by Formula FFormula F 527 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT further wherein X1is bromo, chloro, fluoro, or iodo; X2is oxygen; X3is unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, haloalkyl, halogen, - C(O)-, or -SO2-; and X4is nitrogen wherein the R1bound to X4is absent.

11. The compound of claim 3, wherein the compound is represented by Formula GFormula G further wherein X1is halogen; X2is -N(H)-, oxygen, or sulfur; and each n is independently zero, one, or two.

12. The compound of claim 3, wherein the compound is represented by Formula HFormula H; further wherein X1is bromo, chloro, fluoro, or iodo; X2is oxygen; 528 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT X3is alkylene; -C(O)-;unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, haloalkyl, halogen, -C(O)-, or -SO2-; and X4is nitrogen wherein the R1bound to X4is absent.

13. The compound of any one of claims 3-5, 7-9, or 10-12, wherein L is a bond.529 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT530 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT531 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCTwherein each n1 is independently one, two, or three; each n2 is independently one, two, or three; 532 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT each n3 is independently an integer from one to ten; each R9is independently hydrogen or alkyl; each R10is independently alkyl; R11is hydrogen, alkyl, hydroxymethyl, or haloalkyl; R12is hydrogen, an amino acid side chain, or R9is further bonded to R12to form proline; X6is NR9, oxygen, or sulfur; each X7is independently carbon or nitrogen; and aa is an integer from one to five.533 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT534 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT16. The compound of any one of claims 3, 4, 13, or 15, wherein the compound is selected from the group consisting of 1-[4-(4-{[(3S)-3-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4- yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-4-methylpiperazin-1-yl]methyl}piperidin-1- yl)-3-fluorophenyl]-1,3-diazinane-2,4-dione (23); (3S)-3-(4-(4-((4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3,3- difluoropiperidin-1-yl)methyl)-4-fluoropiperidin-1-yl)phenyl)piperidine-2,6-dione (135); (R)- 3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (140); (S)-3- (3-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (141); (3R)- 3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)-3,3-difluoropiperidin-1-yl)methyl)piperidin-1-yl)-2,5- difluorophenyl)piperidine-2,6-dione (246); (3R)-3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl- 535 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3,3-difluoropiperidin-1- yl)methyl)piperidin-1-yl)-2,6-difluorophenyl)piperidine-2,6-dione (263); 1-(4-(4-((4-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2- (trifluoromethyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)- dione (264); (3R)-3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2-(trifluoromethyl)piperidin-1-yl)methyl)piperidin- 1-yl)phenyl)piperidine-2,6-dione (265); (3R)-3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3,3-difluoropiperidin-1- yl)methyl)piperidin-1-yl)-2,3-difluorophenyl)piperidine-2,6-dione (266); (3R)-3-(4-(4-((4-(4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)- 3,3-difluoropiperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (267); 1-(4-(4- ((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)-3,3-difluoropiperidin-1-yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine- 2,4(1H,3H)-dione (272); (S)-3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)piperazin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (279); (S)-1-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1- yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (280); (S)-1-(4-(4-((4- (4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)- 3-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (281); 1-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin- 7-yl)oxy)phenyl)-3,3-dimethylpiperazin-1-yl)methyl)piperidin-1- yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (282); (S)-1-(4-(4-((4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2- isopropylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (283); 1-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin- 7-yl)oxy)phenyl)-2,2-dimethylpiperazin-1-yl)methyl)piperidin-1- yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (284); 1-(4-(4-((4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3-oxopiperazin-1- yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (285); (S)-1-(4-(4-((2- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)morpholino)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)- dione (288); (S)-3-(4-(4-(((S)-2-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- 536 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)morpholino)methyl)piperidin-1-yl)phenyl)piperidine- 2,6-dione (289); (S)-1-(3-(4-((2-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)morpholino)methyl)piperidin-1- yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (290); (R)-3-(4-(4-(((S)-4-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3- methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,5-difluorophenyl)piperidine-2,6-dione (291); (R)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,5- difluorophenyl)piperidine-2,6-dione (292); rac-(3R)-3-[4-(4-{[4-(4-{[6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}benzenesulfonyl)piperazin-1- yl]methyl}piperidin-1-yl)-2,5-difluorophenyl]piperidine-2,6-dione (293); rac-(3R)-3-[4-(4- {[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl]oxy}benzenesulfonyl)piperidin-1-yl]methyl}piperidin-1-yl)-2,5-difluorophenyl]piperidine- 2,6-dione (294); (R)-3-(4-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,5- difluorophenyl)piperidine-2,6-dione (295); (R)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1- yl)methyl)piperidin-1-yl)-2,5-difluorophenyl)piperidine-2,6-dione (296); (R)-3-(4-(4-(((S)-4- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)- 3-methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,6-difluorophenyl)piperidine-2,6-dione (297); (R)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,6- difluorophenyl)piperidine-2,6-dione (298); (R)-3-(4-(4-((4-((4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)sulfonyl)piperazin-1- yl)methyl)piperidin-1-yl)-2,6-difluorophenyl)piperidine-2,6-dione (299); (R)-3-(4-(4-((4-((4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)sulfonyl)piperidin-1-yl)methyl)piperidin-1-yl)-2,6-difluorophenyl)piperidine- 2,6-dione (300); (R)-3-(4-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,6- difluorophenyl)piperidine-2,6-dione (301); (R)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1- yl)methyl)piperidin-1-yl)-2,6-difluorophenyl)piperidine-2,6-dione (302); (S)-3-(4-(4-(((S)-4- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)- 537 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT 3-methylpiperazin-1-yl)methyl)-4-fluoropiperidin-1-yl)phenyl)piperidine-2,6-dione (303); (S)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1-yl)methyl)-4-fluoropiperidin-1- yl)phenyl)piperidine-2,6-dione (304); (S)-3-(4-(4-((4-((4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)sulfonyl)piperazin-1-yl)methyl)-4- fluoropiperidin-1-yl)phenyl)piperidine-2,6-dione (305); (S)-3-(4-(4-((4-((4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)sulfonyl)piperidin-1- yl)methyl)-4-fluoropiperidin-1-yl)phenyl)piperidine-2,6-dione (306); (S)-3-(4-(4-(((S)-4-(4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2- methylpiperazin-1-yl)methyl)-4-fluoropiperidin-1-yl)phenyl)piperidine-2,6-dione (307); (S)- 3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)-3-methylpiperazin-1-yl)methyl)-4-fluoropiperidin-1-yl)phenyl)piperidine-2,6- dione (308); (R)-3-(4-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,3- difluorophenyl)piperidine-2,6-dione (309); (R)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1- yl)methyl)piperidin-1-yl)-2,3-difluorophenyl)piperidine-2,6-dione (310); (R)-3-(4-(4-((4-((4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)sulfonyl)piperazin-1-yl)methyl)piperidin-1-yl)-2,3-difluorophenyl)piperidine- 2,6-dione (311); (R)-3-(4-(4-((4-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)sulfonyl)piperidin-1-yl)methyl)piperidin-1-yl)-2,3- difluorophenyl)piperidine-2,6-dione (312); (R)-3-(4-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1- yl)methyl)piperidin-1-yl)-2,3-difluorophenyl)piperidine-2,6-dione (313); (R)-3-(4-(4-(((R)-4- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)- 3-methylpiperazin-1-yl)methyl)piperidin-1-yl)-2,3-difluorophenyl)piperidine-2,6-dione (314); (R)-3-(4-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine- 2,6-dione (315); (S)-1-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1-yl)methyl)piperidin-1- yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (316); (R)-1-(4-(4-((4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1- yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (317); (R)-1-(4-(4-((4- 538 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)- 3-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (318); (R)-3-(4-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine- 2,6-dione (319); (R)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (320); (R)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)-2-methylpiperazin-1- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (321); 1-(4-(4-((4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)piperazin-1- yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (323); 1-(4-(4-((4-((4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)sulfonyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine- 2,4(1H,3H)-dione (324); 1-(4-(4-((4-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)sulfonyl)piperidin-1-yl)methyl)piperidin-1- yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (325); (R)-3-(4-(4-((4-((4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)sulfonyl)piperazin-1- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (326); (R)-3-(4-(4-((4-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)phenyl)sulfonyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (327); (S)-3-(4-(4-(((S)-4-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)phenyl)-3-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine- 2,6-dione (328); rac-1-[4-(4-{[(3R)-3-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-4-methylpiperazin-1-yl]methyl}piperidin-1- yl)phenyl]-1,3-diazinane-2,4-dione (329); (3R)-3-[4-(4-{[(3RS)-3-(4-{[6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-4-methylpiperazin-1- yl]methyl}piperidin-1-yl)phenyl]piperidine-2,6-dione (330); 1-[4-(4-{[4-(4-{[6-bromo-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2,2- dimethylpiperazin-1-yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3-diazinane-2,4-dione (331); 1-[4-(4-{[4-(4-{[6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl]oxy}phenyl)-2,2-dimethylpiperazin-1-yl]methyl}piperidin-1-yl)phenyl]-1,3- diazinane-2,4-dione (333); (3R)-3-[4-(4-{[4-(4-{[6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2,2-dimethylpiperazin-1-yl]methyl}piperidin-1- 539 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT yl)phenyl]piperidine-2,6-dione (334); 1-[5-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol- 4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2,2-dimethylpiperidin-1- yl]methyl}piperidin-1-yl)pyridin-2-yl]-1,3-diazinane-2,4-dione (335); 1-[4-(4-{[4-(4-{[6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2,2- dimethylpiperidin-1-yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3-diazinane-2,4-dione (336); 1-[4-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl]oxy}phenyl)-3,3-dimethylpiperidin-1-yl]methyl}piperidin-1-yl)-3- fluorophenyl]-1,3-diazinane-2,4-dione (338); 1-[4-(4-{[(2S)-4-(4-{[6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2-methylpiperazin-1- yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3-diazinane-2,4-dione (339); 1-[4-(4-{[(3S)-4- (4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}-2- fluorophenyl)-3-methylpiperazin-1-yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3-diazinane- 2,4-dione (341); rac-1-[4-(4-{[(4R)-4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-3,3-dimethylpiperidin-1-yl]methyl}piperidin-1- yl)phenyl]-1,3-diazinane-2,4-dione (346); (3R)-3-[4-(4-{[(4RS)-4-(4-{[6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2,2- dimethylpiperidin-1-yl]methyl}piperidin-1-yl)phenyl]piperidine-2,6-dione (350); rac-1-[4-(4- {[(4R)-4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl]oxy}phenyl)-2,2-dimethylpiperidin-1-yl]methyl}piperidin-1-yl)phenyl]-1,3-diazinane-2,4- dione (351); 1-[4-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl]oxy}phenyl)-2,2-dimethylpiperazin-1-yl]methyl}piperidin-1-yl)-3- fluorophenyl]-1,3-diazinane-2,4-dione (352); 1-[4-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2,2-dimethylpiperazin-1- yl]methyl}piperidin-1-yl)-2-fluorophenyl]-1,3-diazinane-2,4-dione (353); rac-(3R)-3-[2-(4- {[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl]oxy}phenyl)-2,2-dimethylpiperazin-1-yl]methyl}piperidin-1-yl)pyridin-4-yl]piperidine- 2,6-dione (354); 1-[3-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2,2-dimethylpiperazin-1-yl]methyl}piperidin-1- yl)phenyl]-1,3-diazinane-2,4-dione (355); rac-(3R)-3-[4-(4-{[4-(4-{[6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-2,2- dimethylpiperazin-1-yl]methyl}piperidin-1-yl)-2,6-difluorophenyl]piperidine-2,6-dione (356); (3RS)-3-[4-(4-{[(3S)-4-(4-{[6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-3-methylpiperazin-1-yl]methyl}piperidin-1-yl)-2,6- 540 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT difluorophenyl]piperidine-2,6-dione (357); (3R)-3-[4-(4-{[(3R)-4-(4-{[6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}-2,6-difluorophenyl)-3- methylpiperazin-1-yl]methyl}piperidin-1-yl)phenyl]piperidine-2,6-dione (358); rac-1-[4-(4- {[(3R)-4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl]oxy}-2,6-difluorophenyl)-3-methylpiperazin-1-yl]methyl}piperidin-1-yl)phenyl]-1,3- diazinane-2,4-dione (359); 1-[5-(4-{[(3R)-4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl]oxy}-2,6-difluorophenyl)-3-methylpiperazin-1- yl]methyl}piperidin-1-yl)pyridin-2-yl]-1,3-diazinane-2,4-dione (360); 1-[3-(4-{[(2R)-2-(4- {[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl]oxy}phenyl)morpholin-4-yl]methyl}piperidin-1-yl)phenyl]-1,3-diazinane-2,4-dione (361); 1-[3-(4-{[(2S)-2-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin- 7-yl]oxy}phenyl)morpholin-4-yl]methyl}piperidin-1-yl)phenyl]-1,3-diazinane-2,4-dione (362); (3R)-3-[4-(4-{[(2S)-2-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)morpholin-4-yl]methyl}piperidin-1- yl)phenyl]piperidine-2,6-dione (363); 1-[3-(4-{[(3S)-4-(4-{[6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-3-methylpiperazin-1- yl]methyl}piperidin-1-yl)phenyl]-1,3-diazinane-2,4-dione (364); (3RS)-3-[3-(4-{[(3S)-4-(4- {[6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)-3- methylpiperazin-1-yl]methyl}piperidin-1-yl)phenyl]piperidine-2,6-dione (365); (3RS)-3-[2- (4-{[(3S)-4-(4-{[6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl]oxy}phenyl)-3-methylpiperazin-1-yl]methyl}piperidin-1-yl)pyridin-4-yl]piperidine-2,6- dione (366); 1-[3-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl]oxy}phenyl)piperidin-1-yl]methyl}piperidin-1-yl)phenyl]-1,3-diazinane-2,4- dione (367); 1-[4-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl]oxy}phenyl)piperidin-1-yl]methyl}piperidin-1-yl)phenyl]-1,3-diazinane-2,4- dione (368); rac-(3R)-3-[4-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)piperidin-1-yl]methyl}piperidin-1-yl)-2,6- difluorophenyl]piperidine-2,6-dione (369); 1-[4-(4-{[4-(4-{[6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)piperidin-1-yl]methyl}piperidin-1- yl)-2-fluorophenyl]-1,3-diazinane-2,4-dione (370); and 1-[4-(4-{[4-(4-{[6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}phenyl)piperidin-1- yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3-diazinane-2,4-dione (371). 541 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT 17. The compound of any one of claims 3, 5, 13, or 15, wherein the compound is selected from the group consisting of (R)-1-(4-(4-((4-(5-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl)oxy)-3-fluoropyridin-2-yl)-2-methylpiperazin-1- yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (286); and (S)-1-(4-(4- ((4-(5-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-3- fluoropyridin-2-yl)-2-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)dihydropyrimidine- 2,4(1H,3H)-dione (287); 1-[4-(4-{[(2S)-4-(5-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl]oxy}-3-fluoropyridin-2-yl)-2-methylpiperazin-1- yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3-diazinane-2,4-dione (340); 1-[4-(4-{[(3S)-4- (5-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}pyridin- 2-yl)-3-methylpiperazin-1-yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3-diazinane-2,4-dione (343); 1-[4-(4-{[(3S)-4-(5-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl]oxy}pyridin-2-yl)-3-methylpiperazin-1-yl]methyl}piperidin-1-yl)phenyl]-1,3- diazinane-2,4-dione (345); and (3R)-3-[4-(4-{[(3S)-4-(5-{[6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}pyridin-2-yl)-3-methylpiperazin-1- yl]methyl}piperidin-1-yl)phenyl]piperidine-2,6-dione (347).

18. The compound of any one of claims 3, 7, 13, or 15, wherein the compound is selected from the group consisting of (R)-4-((6-chloro-2-(4-(4-((1-(4-(2,6-dioxopiperidin-3- yl)phenyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)- N-phenylbenzamide (136); (S)-4-((6-chloro-2-(4-(4-((1-(3-(2,6-dioxopiperidin-3- yl)phenyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)- N-phenylbenzamide (137); (S)-4-((6-chloro-2-(4-(4-((1-(4-(2,6-dioxopiperidin-3-yl)-3- fluorophenyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)-N-phenylbenzamide (172); and (S)-4-((6-chloro-2-(4-(4-((1-(4-(2,6-dioxopiperidin-3- yl)-2-fluorophenyl)piperidin-4-yl)methyl)piperazin-1-yl)phenyl)-3H-imidazo[4,5-b]pyridin- 7-yl)oxy)-N-phenylbenzamide (173).

19. The compound of any one of claims 3, 8, 13, or 15, wherein the compound is selected from the group consisting of (R)-3-(4-(4-((4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1- yl)-3H-imidazo[4,5-b]pyridin-2-yl)benzyl)piperazin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (138); (S)-3-(3-(4-((4-(4-(6-bromo-7-(4-(4- chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)benzyl)piperazin-1- 542 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (139); (S)-3-(4-(4-((4-(4-(6-bromo-7- (4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)benzyl)piperazin-1- yl)methyl)piperidin-1-yl)-2-fluorophenyl)piperidine-2,6-dione (170); (S)-3-(4-(4-((4-(4-(6- bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2- yl)benzyl)piperazin-1-yl)methyl)piperidin-1-yl)-3-fluorophenyl)piperidine-2,6-dione (171); and (R)-3-(4-(4-((4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5- b]pyridin-2-yl)phenyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (245).

20. The compound of any one of claims 3, 9, 13, or 15, wherein the compound is selected from the group consisting of (S)-3-(6-((S)-3-(2-(4-(4-(6-bromo-7-(4-((5-methylisoxazol-3- yl)methyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)phenyl)piperazin-1- yl)ethyl)pyrrolidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (160); (R)-3-(4-((4-((4-(4-(6- bromo-7-(4-((5-methylisoxazol-3-yl)methyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2- yl)phenyl)piperazin-1-yl)methyl)cyclohexyl)oxy)phenyl)piperidine-2,6-dione (161); (R)-3- (4-(4-((4-(4-(6-bromo-7-(4-((5-methylisoxazol-3-yl)methyl)piperazin-1-yl)-3H-imidazo[4,5- b]pyridin-2-yl)phenyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (162); 3-(3-(4-((4-(4-(6-bromo-7-(4-((5-methylisoxazol-3-yl)methyl)piperazin-1-yl)-3H- imidazo[4,5-b]pyridin-2-yl)phenyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine- 2,6-dione (163); (S)-4-(4-((4-(4-(6-bromo-7-(4-((5-methylisoxazol-3-yl)methyl)piperazin-1- yl)-3H-imidazo[4,5-b]pyridin-2-yl)phenyl)piperazin-1-yl)methyl)piperidin-1-yl)-N-(2,6- dioxopiperidin-3-yl)picolinamide (164); (S)-5-(4-((4-(4-(6-bromo-7-(4-((5-methylisoxazol-3- yl)methyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)phenyl)piperazin-1- yl)methyl)piperidin-1-yl)-N-(2,6-dioxopiperidin-3-yl)picolinamide (165); (S)-3-(4-((R)-3-((4- (4-(6-bromo-7-(4-((5-methylisoxazol-3-yl)methyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin- 2-yl)phenyl)piperazin-1-yl)methyl)pyrrolidin-1-yl)phenyl)piperidine-2,6-dione (166); (S)-3- (4-((S)-3-((4-(4-(6-bromo-7-(4-((5-methylisoxazol-3-yl)methyl)piperazin-1-yl)-3H- imidazo[4,5-b]pyridin-2-yl)phenyl)piperazin-1-yl)methyl)pyrrolidin-1-yl)phenyl)piperidine- 2,6-dione (167); (R)-3-(4-(4-((4-(4-(6-bromo-7-(4-((5-methylisoxazol-3-yl)methyl)piperazin- 1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)phenyl)piperazin-1-yl)methyl)piperidin-1-yl)-2- fluorophenyl)piperidine-2,6-dione (168); and (R)-3-(4-(4-((4-(4-(6-bromo-7-(4-((5- methylisoxazol-3-yl)methyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2- yl)phenyl)piperazin-1-yl)methyl)piperidin-1-yl)-3-fluorophenyl)piperidine-2,6-dione (169). 543 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT 21. The compound of any one of claims 3, 4, 14, or 15, wherein the compound is selected from the group consisting of (R)-3-(4-(4-(2-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4- yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidin-4-yl)acetyl)piperazin-1- yl)phenyl)piperidine-2,6-dione (24); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-(4-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)piperazine-1-carbonyl)cyclohexyl)methyl)benzamide (25); (S)-4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(4-(((1-(5-(2,6- dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)amino)cyclohexyl)-N- methylbenzamide (26); (S)-4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)-N-(3-(((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4- yl)methyl)amino)propyl)benzamide (27); (S)-4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((1-((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3- yl)piperidin-4-yl)methyl)piperidin-4-yl)methyl)benzamide (28); (S)-4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(2-(((1-(5-(2,6- dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)(methyl)amino)ethyl)benzamide (29); (S)-4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3- (((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)amino)-2,2- dimethylpropyl)benzamide (30); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-((1-((1-(5-((S)-2,6-dioxopiperidin-3-yl)pyridin-3- yl)piperidin-4-yl)methyl)pyrrolidin-3-yl)methyl)benzamide (31); (S)-4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(4-(((1-(5-(2,6- dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)amino)butyl)benzamide (32); (S)-4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(2-(1- ((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)piperidin-4- yl)ethyl)benzamide (33); (S)-3-(5-(4-((4-((1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidin-4-yl)methyl)piperidin-1- yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (34); (S)-3-(5-(4-((4-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperazin-1-yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (35); (3S)-3-(5-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)-3-methylpiperazin-1-yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6- dione (36); (S)-4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- 544 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT yl)oxy)-N-(3-(((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4- yl)methyl)amino)propyl)-N-methylbenzamide (37); (S)-N-(4-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-methylbenzamido)cyclohexyl)-1- ((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)piperidine-4-carboxamide (38); (S)-N-(3-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzamido)propyl)-1-((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4- yl)methyl)piperidine-4-carboxamide (39); (S)-4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((1-(1-((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3- yl)piperidin-4-yl)methyl)piperidine-4-carbonyl)piperidin-4-yl)methyl)benzamide (40); (S)-N- (2-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzamido)ethyl)-1-((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4- yl)methyl)-N-methylpiperidine-4-carboxamide (41); (S)-N-(3-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzamido)-2,2-dimethylpropyl)-1-((1- (5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)piperidine-4-carboxamide (42); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N- ((1-(1-((1-(5-((S)-2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)piperidine-4- carbonyl)pyrrolidin-3-yl)methyl)benzamide (43); (S)-N-(4-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzamido)butyl)-1-((1-(5-(2,6- dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)piperidine-4-carboxamide (44); (S)- N-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzamido)cyclohexyl)-1-((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4- yl)methyl)piperidine-4-carboxamide (45); (S)-4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(2-(1-(1-((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3- yl)piperidin-4-yl)methyl)piperidine-4-carbonyl)piperidin-4-yl)ethyl)benzamide (46); (S)-3- (5-(4-((4-(4-((1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidin-4-yl)methyl)piperidine-1-carbonyl)piperidin-1-yl)methyl)piperidin- 1-yl)pyridin-3-yl)piperidine-2,6-dione (47); (S)-3-(5-(4-((4-(4-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazine-1- carbonyl)piperidin-1-yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (48); (3S)-3- (5-(4-((4-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)-3-methylpiperazine-1-carbonyl)piperidin-1-yl)methyl)piperidin-1- yl)pyridin-3-yl)piperidine-2,6-dione (49); (S)-N-(3-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-methylbenzamido)propyl)-1-((1-(5- 545 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT (2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4-yl)methyl)piperidine-4-carboxamide (50); (S)-4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(4- (((1-(5-(2,6-dioxopiperidin-3-yl)pyridin-3-yl)piperidin-4- yl)methyl)amino)cyclohexyl)benzamide (51); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(4-(3-(((4-((S)-2,6-dioxopiperidin-3- yl)phenyl)amino)methyl)piperidine-1-carbonyl)benzyl)benzamide (52); 4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(4-(5-(4-((S)-2,6- dioxopiperidin-3-yl)phenyl)octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)benzyl)benzamide (53); (3S)-3-(4-(6-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)piperidine-3-carbonyl)-2,6-diazaspiro[3.4]octan-2- yl)phenyl)piperidine-2,6-dione (54); (3S)-3-(4-(5-(2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)morpholin-2- yl)acetyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (55); 4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4- (2-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2,6-diazaspiro[3.4]octane-6- carbonyl)cyclohexyl)methyl)benzamide (56); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-(3-(((4-((S)-2,6-dioxopiperidin-3- yl)phenyl)amino)methyl)piperidine-1-carbonyl)benzyl)benzamide (57); (3S)-3-(4-(((1-(2-(4- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)morpholin-2-yl)acetyl)piperidin-3-yl)methyl)amino)phenyl)piperidine-2,6- dione (58); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)-N-((2R)-1-(5-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)hexahydropyrrolo[3,4-c]pyrrol- 2(1H)-yl)-3-methyl-1-oxobutan-2-yl)benzamide (59); (S)-3-(4-(6-((4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-L-prolyl)-2,6- diazaspiro[3.4]octan-2-yl)phenyl)piperidine-2,6-dione (60); (S)-3-(4-(6-(2-(1-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidin-4- yl)acetyl)-2,6-diazaspiro[3.4]octan-2-yl)phenyl)piperidine-2,6-dione (61); (S)-3-(4-(6-(2-(4- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperazin-1-yl)acetyl)-2,6-diazaspiro[3.4]octan-2-yl)phenyl)piperidine-2,6- dione (62); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)-N-((2R)-1-(3-(((4-((S)-2,6-dioxopiperidin-3-yl)phenyl)amino)methyl)piperidin-1-yl)- 3-methyl-1-oxobutan-2-yl)benzamide (63); (3S)-3-(4-(5-(2-(4-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazin-1- 546 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT yl)acetyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (64); 4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((R)-1-(2- (4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2,6-diazaspiro[3.4]octan-6-yl)-3-methyl-1-oxobutan- 2-yl)benzamide (65); (3S)-3-(4-(6-(2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)morpholin-2-yl)acetyl)-2,6-diazaspiro[3.4]octan-2- yl)phenyl)piperidine-2,6-dione (66); (S)-4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-(4-(2-(4-(2,6-dioxopiperidin-3-yl)phenyl)-2,6- diazaspiro[3.4]octane-6-carbonyl)benzyl)benzamide (67); (3S)-3-(4-(5-(2-(1-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidin-4- yl)acetyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (68); (S)-1-(4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N- ((1-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)-N-methylpiperidine-4- carboxamide (69); (S)-3-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzamido)methyl)-N-((1-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4- yl)methyl)-N-methylbenzamide (70); 1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)piperidin-4-yl)methyl)-N-methylpiperidine-3-carboxamide (71); (3S)-3-(4-(((1-(2- (4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperazin-1-yl)acetyl)piperidin-3-yl)methyl)amino)phenyl)piperidine-2,6- dione (72); (3S)-3-(4-(5-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)-L-prolyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)- yl)phenyl)piperidine-2,6-dione (73); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-(((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)piperidin-4-yl)methyl)(methyl)carbamoyl)cyclohexyl)methyl)benzamide (74); (S)- 1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)-N-((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)-N- methylpyrrolidine-2-carboxamide (75); (S)-2-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4- yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidin-4-yl)-N-((1-(4-(2,6-dioxopiperidin- 3-yl)phenyl)piperidin-4-yl)methyl)-N-methylacetamide (76); (3S)-3-(4-(((1-(2-(1-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidin-4-yl)acetyl)piperidin-3-yl)methyl)amino)phenyl)piperidine-2,6- dione (77); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)-N-(((1S,4r)-4-(5-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)octahydropyrrolo[3,4- 547 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT c]pyrrole-2-carbonyl)cyclohexyl)methyl)benzamide (78); (S)-2-(4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazin-1-yl)-N- ((1-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)-N-methylacetamide (79); 4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((R)-1- (((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)(methyl)amino)-3-methyl- 1-oxobutan-2-yl)benzamide (80); 2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)morpholin-2-yl)-N-((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)piperidin-4-yl)methyl)-N-methylacetamide (81); (3S)-3-(4-(5-(1-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-3- carbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (82); (S)-4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-(2-(4- (2,6-dioxopiperidin-3-yl)phenyl)-2,6-diazaspiro[3.4]octane-6-carbonyl)benzyl)benzamide (83); (S)-4-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzamido)methyl)-N-((1-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)- N-methylbenzamide (84); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)-N-(3-(5-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)octahydropyrrolo[3,4- c]pyrrole-2-carbonyl)benzyl)benzamide (85); (S)-3-(4-(6-(1-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4-carbonyl)-2,6- diazaspiro[3.4]octan-2-yl)phenyl)piperidine-2,6-dione (86); (3S)-3-(4-(5-(1-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4- carbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (87); (S)-1-(4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N- (1-(4-(2,6-dioxopiperidin-3-yl)phenyl)-4-methylpiperidin-4-yl)piperidine-4-carboxamide (88); (S)-3-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzamido)methyl)-N-(1-(4-(2,6-dioxopiperidin-3-yl)phenyl)-4-methylpiperidin-4- yl)benzamide (89); 1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)-N-(1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-4-methylpiperidin- 4-yl)piperidine-3-carboxamide (90); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-4- methylpiperidin-4-yl)carbamoyl)cyclohexyl)methyl)benzamide (91); (S)-1-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-(1-(4-((S)- 2,6-dioxopiperidin-3-yl)phenyl)-4-methylpiperidin-4-yl)pyrrolidine-2-carboxamide (92); (S)- 2-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- 548 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT yl)oxy)benzoyl)piperidin-4-yl)-N-(1-(4-(2,6-dioxopiperidin-3-yl)phenyl)-4-methylpiperidin- 4-yl)acetamide (93); (S)-2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazin-1-yl)-N-(1-(4-(2,6-dioxopiperidin-3- yl)phenyl)-4-methylpiperidin-4-yl)acetamide (94); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol- 4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((R)-1-((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)-4-methylpiperidin-4-yl)amino)-3-methyl-1-oxobutan-2-yl)benzamide (95); 4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((S)-1-((1- (4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-4-methylpiperidin-4-yl)amino)-1-oxopropan-2-yl)-N- methylbenzamide (96); 2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)morpholin-2-yl)-N-(1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-4- methylpiperidin-4-yl)acetamide (97); (S)-4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-(1-((1-(4-(2,6-dioxopiperidin-3-yl)phenyl)-4- methylpiperidin-4-yl)amino)-2-methyl-1-oxopropan-2-yl)benzamide (98); (S)-4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(4-((1-(4-(2,6- dioxopiperidin-3-yl)phenyl)-4-methylpiperidin-4-yl)carbamoyl)benzyl)benzamide (99); 3- ((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzamido)methyl)-N-((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)pyrrolidin-3- yl)methyl)-N-methylbenzamide (100); 1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)pyrrolidin-3-yl)methyl)-N-methylpiperidine-3-carboxamide (101); 4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-(((1-(4- ((S)-2,6-dioxopiperidin-3-yl)phenyl)pyrrolidin-3- yl)methyl)(methyl)carbamoyl)cyclohexyl)methyl)benzamide (102); (2S)-1-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-((1-(4-((S)- 2,6-dioxopiperidin-3-yl)phenyl)pyrrolidin-3-yl)methyl)-N-methylpyrrolidine-2-carboxamide (103); 2-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidin-4-yl)-N-((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)pyrrolidin-3- yl)methyl)-N-methylacetamide (104); 2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazin-1-yl)-N-((1-(4-((S)-2,6- dioxopiperidin-3-yl)phenyl)pyrrolidin-3-yl)methyl)-N-methylacetamide (105); 4-((6-chloro- 2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((2R)-1-(((1-(4- ((S)-2,6-dioxopiperidin-3-yl)phenyl)pyrrolidin-3-yl)methyl)(methyl)amino)-3-methyl-1- oxobutan-2-yl)benzamide (106); 2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- 549 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)morpholin-2-yl)-N-((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)pyrrolidin-3-yl)methyl)-N-methylacetamide (107); 4-((4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzamido)methyl)-N-((1-(4- ((S)-2,6-dioxopiperidin-3-yl)phenyl)pyrrolidin-3-yl)methyl)-N-methylbenzamide (108); 4- ((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-((R)- 4-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2-methylpiperazine-1-carbonyl)benzyl)benzamide (109); (S)-3-(4-((R)-4-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)piperidine-4-carbonyl)-3-methylpiperazin-1- yl)phenyl)piperidine-2,6-dione (110); (3S)-3-(4-((3R)-4-(1-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-3-carbonyl)-3- methylpiperazin-1-yl)phenyl)piperidine-2,6-dione (111); 4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1R,4r)-4-((R)-4-(4-((S)-2,6- dioxopiperidin-3-yl)phenyl)-2-methylpiperazine-1-carbonyl)cyclohexyl)methyl)benzamide (112); (S)-3-(4-((R)-4-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)-L-prolyl)-3-methylpiperazin-1-yl)phenyl)piperidine-2,6-dione (113); (S)-3-(4-((R)-4-(2-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)piperidin-4-yl)acetyl)-3-methylpiperazin-1-yl)phenyl)piperidine- 2,6-dione (114); (S)-3-(4-((R)-4-(2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazin-1-yl)acetyl)-3-methylpiperazin-1- yl)phenyl)piperidine-2,6-dione (115); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-((R)-1-((R)-4-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2- methylpiperazin-1-yl)-3-methyl-1-oxobutan-2-yl)benzamide (116); (3S)-3-(4-((3R)-4-(2-(4- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)morpholin-2-yl)acetyl)-3-methylpiperazin-1-yl)phenyl)piperidine-2,6-dione (117); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N- (4-((R)-4-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2-methylpiperazine-1- carbonyl)benzyl)benzamide (118); (S)-3-(4-(4-((1-(1-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4-carbonyl)piperidin-4- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (119); (S)-4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-(4-((1-(4-(2,6- dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)piperidine-1-carbonyl)benzyl)benzamide (120); (3S)-3-(4-(4-((1-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)piperidine-3-carbonyl)piperidin-4-yl)methyl)piperidin-1- 550 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT yl)phenyl)piperidine-2,6-dione (121); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1r,4r)-4-(4-((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)piperidin-4-yl)methyl)piperidine-1-carbonyl)cyclohexyl)methyl)benzamide (122); (S)-3-(4-(4-((1-((4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)-L-prolyl)piperidin-4-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (123); (S)-3-(4-(4-((1-(2-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)piperidin-4-yl)acetyl)piperidin-4-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (124); (S)-3-(4-(4-((1-(2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazin-1-yl)acetyl)piperidin-4- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (125); 4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((R)-1-(4-((1-(4-((S)-2,6- dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)piperidin-1-yl)-3-methyl-1-oxobutan-2- yl)benzamide (126); (3S)-3-(4-(4-((1-(2-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)morpholin-2-yl)acetyl)piperidin-4- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (127); (S)-4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(4-(4-((1-(4-(2,6- dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)piperidine-1-carbonyl)benzyl)benzamide (128); (3S)-3-(4-(((1-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)piperidine-3-carbonyl)piperidin-3- yl)methyl)amino)phenyl)piperidine-2,6-dione (129); (3S)-3-(4-(((1-((4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-L-prolyl)piperidin- 3-yl)methyl)amino)phenyl)piperidine-2,6-dione (130); 4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-(3-(((4-((S)-2,6- dioxopiperidin-3-yl)phenyl)amino)methyl)piperidine-1- carbonyl)cyclohexyl)methyl)benzamide (131); 1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol- 4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-((1-(4-((R)-2,6-dioxopiperidin-3- yl)phenyl)pyrrolidin-3-yl)methyl)-N-methylpiperidine-4-carboxamide (132); (S)-3-(5-(4- (((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)-3-methylpiperazin-1-yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6- dione (133); (S)-3-(5-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-3-methylpiperazin-1-yl)methyl)piperidin-1- yl)pyridin-3-yl)piperidine-2,6-dione (134); (S)-3-(3-(4-((4-((1-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)piperidin-4- 551 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (142); (S)-3-(3- (4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)-2-methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (144); (S)-3-(3-(4-((4-((1-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)piperidin-4-yl)methyl)piperidin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (146); (S)-3-(3-(4-((4-(4-((6-bromo-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (147); (S)-3-(3-(4-(((R)-4-(4-((6-bromo-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-2-methylpiperazin-1- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (148); (S)-3-(3-(4-((4-(4-(4-((6-chloro- 2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)piperidine-1- carbonyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (150); (R)-3-(4- (4-((4-((1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)piperidin-4-yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine- 2,6-dione (151); (R)-3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)piperazin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (152); (R)-3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2-methylpiperazin-1- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (153); (R)-3-(4-(4-((4-((1-(4-((6- bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidin-4-yl)methyl)piperidin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (155); (R)-3-(4-(4-((4-(4-((6-bromo-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperazin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (156); (R)-3-(4-(4-(((R)-4-(4-((6-bromo-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-2-methylpiperazin-1- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (157); (R)-3-(4-(4-((4-(4-(4-((6-chloro- 2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)piperidine-1- carbonyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (159); (S)-3-(3- ((R)-4-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidine-4-carbonyl)-3-methylpiperazin-1-yl)phenyl)piperidine-2,6-dione (181); 4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)- N-(((1R,4r)-4-((R)-4-(3-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2-methylpiperazine-1- carbonyl)cyclohexyl)methyl)benzamide (182); (3S)-3-(4-(4-(4-(4-((6-bromo-2-(1,3-dimethyl- 552 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-1-methylpiperazine-2- carbonyl)piperazin-1-yl)phenyl)piperidine-2,6-dione (188); (3S)-3-(4-(4-(4-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-1- methylpiperazine-2-carbonyl)piperazin-1-yl)phenyl)piperidine-2,6-dione (189); (3S)-3-(4-(7- (4-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)-1-methylpiperazine-2-carbonyl)-2,7-diazaspiro[4.5]decan-2- yl)phenyl)piperidine-2,6-dione (206); (3S)-3-(4-(5-(4-(4-((6-bromo-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-1-methylpiperazine-2- carbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (214); 4-(4- ((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N- (1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-4-methylpiperidin-4-yl)-1-methylpiperazine-2- carboxamide (226); 2-((R)-1-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)pyrrolidin-3-yl)-N-((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)pyrrolidin-3-yl)methyl)-N-methylacetamide (227); 4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((1S,4r)-4-(((1-(4-((S)-2,6- dioxopiperidin-3-yl)phenyl)pyrrolidin-3- yl)methyl)(methyl)carbamoyl)cyclohexyl)benzamide (228); (S)-3-(4-((R)-4-(1-(4-((6-bromo- 2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4- carbonyl)-3-methylpiperazin-1-yl)phenyl)piperidine-2,6-dione (229); 4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-((R)-4-(4-((S)-2,6- dioxopiperidin-3-yl)phenyl)-2-methylpiperazin-1-yl)-3-oxopropyl)benzamide (230); 4-((6- bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(2-((R)-4- (4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2-methylpiperazin-1-yl)-2-oxoethyl)-N- methylbenzamide (231); (3S)-3-(4-((3R)-4-(4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4- yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-1-methylpiperazine-2-carbonyl)-3- methylpiperazin-1-yl)phenyl)piperidine-2,6-dione (232); (S)-1-(4-((6-bromo-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-((1-(4-(2,6-dioxopiperidin- 3-yl)phenyl)piperidin-4-yl)methyl)-N-methylpiperidine-4-carboxamide (233); 4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((1S,4r)-4-(((1-(4- ((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-4- yl)methyl)(methyl)carbamoyl)cyclohexyl)benzamide (234); (R)-3-(4-(4-((4-(2-(1-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidin-4-yl)ethyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine- 553 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT 2,6-dione (247); (R)-3-(4-(4-((4-((1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidin-4-yl)methoxy)piperidin-1- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (248); (R)-3-(4-(4-((4-((1-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidin-4-yl)methyl)piperidin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (249); (R)-3-(5-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2-methylpiperazin-1- yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (250); (R)-3-(5-(4-(((R)-4-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-3- methylpiperazin-1-yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (251); (R)-3- (5-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)-2-(hydroxymethyl)piperazin-1-yl)methyl)piperidin-1-yl)pyridin-3- yl)piperidine-2,6-dione (252); (3R)-3-(5-(4-((3-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4- yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-3,6-diazabicyclo[3.1.1]heptan-6- yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (253); (R)-3-(5-(4-(((R)-4-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2- methylpiperazin-1-yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (254); (R)-3- (5-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)-2-(hydroxymethyl)piperazin-1-yl)methyl)piperidin-1-yl)pyridin-3- yl)piperidine-2,6-dione (255); (R)-3-(5-(4-(((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol- 4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-3-methylpiperazin-1-yl)methyl)piperidin- 1-yl)pyridin-3-yl)piperidine-2,6-dione (256); (R)-3-(3-(4-(((S)-4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2-methylpiperazin-1- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (257); (R)-3-(3-(4-(((R)-4-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-3- methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (258); (R)-3-(3-(4- (((S)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)-2-(hydroxymethyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine- 2,6-dione (259); (3R)-3-(3-(4-((3-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-3,6-diazabicyclo[3.1.1]heptan-6-yl)methyl)piperidin- 1-yl)phenyl)piperidine-2,6-dione (260); (R)-3-(3-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2-(hydroxymethyl)piperazin-1- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (261); (R)-3-(3-(4-(((S)-4-(4-((6- 554 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-3- methylpiperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (262); (R)-1-(4-(4- ((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)-2-(hydroxymethyl)piperazin-1-yl)methyl)piperidin-1- yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (268); (R)-3-(4-(4-(((S)-4-(4-((6-chloro-2- (1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2- (hydroxymethyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (269); (R)- 3-(4-(4-(((R)-4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)-2-(hydroxymethyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine- 2,6-dione (270); (S)-1-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2-(hydroxymethyl)piperazin-1-yl)methyl)piperidin- 1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (271); 3-(4-(4-((4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-3- (fluoromethyl)piperazin-1-yl)methyl)piperidin-1-yl)-2-fluorophenyl)piperidine-2,6-dione (273); 3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin- 7-yl)oxy)benzyl)-3-(fluoromethyl)piperazin-1-yl)methyl)piperidin-1-yl)-3- fluorophenyl)piperidine-2,6-dione (274); (3S)-3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2-(fluoromethyl)piperazin-1- yl)methyl)piperidin-1-yl)-2-fluorophenyl)piperidine-2,6-dione (275); (3R)-3-(4-(4-((4-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)benzyl)-2- (fluoromethyl)piperazin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (276); (3S)- 3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)-3-(fluoromethyl)piperazin-1-yl)methyl)piperidin-1-yl)-3- fluorophenyl)piperidine-2,6-dione (277); (3S)-3-(4-(4-((4-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl)oxy)benzyl)-2-(fluoromethyl)piperazin-1-yl)methyl)piperidin-1-yl)-3- fluorophenyl)piperidine-2,6-dione (278); and (R)-3-(4-(4-((4-(4-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)phenyl)piperazine-1- carbonyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (322).

22. The compound of any one of claims 3, 6, 14, or 15, wherein the compound is selected from the group consisting of 4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5- b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-(4-(3-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperazine-1- 555 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT carbonyl)cyclohexyl)methyl)benzamide (174); (3S)-3-(3-(((1-(1-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4- carbonyl)piperidin-3-yl)methyl)amino)phenyl)piperidine-2,6-dione (175); 4-((6-bromo-2- (1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-(3-(((3- ((S)-2,6-dioxopiperidin-3-yl)phenyl)amino)methyl)piperidine-1- carbonyl)cyclohexyl)methyl)benzamide (176); (3S)-3-(3-(5-(1-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4- carbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (177); 4-((6- bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4- (5-(3-((S)-2,6-dioxopiperidin-3-yl)phenyl)octahydropyrrolo[3,4-c]pyrrole-2- carbonyl)cyclohexyl)methyl)benzamide (178); (S)-3-(3-(6-(1-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4-carbonyl)-2,6- diazaspiro[3.4]octan-2-yl)phenyl)piperidine-2,6-dione (179); 4-((6-bromo-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-(2-(3-((S)-2,6- dioxopiperidin-3-yl)phenyl)-2,6-diazaspiro[3.4]octane-6- carbonyl)cyclohexyl)methyl)benzamide (180); (S)-3-(4-(4-(1-(4-((6-chloro-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4- carbonyl)piperazin-1-yl)phenyl)piperidine-2,6-dione (183); 4-((6-bromo-2-(1,3-dimethyl-1H- pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-(4-(4-((S)-2,6- dioxopiperidin-3-yl)phenyl)piperazine-1-carbonyl)cyclohexyl)methyl)benzamide (184); (S)- 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(2-(4- (4-(2,6-dioxopiperidin-3-yl)phenyl)piperazin-1-yl)-2-oxoethyl)benzamide (185); (S)-4-((6- bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-(4-(4- (2,6-dioxopiperidin-3-yl)phenyl)piperazin-1-yl)-3-oxopropyl)benzamide (186); (3S)-3-(4-(4- (3-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)pyrrolidin-3-yl)propanoyl)piperazin-1-yl)phenyl)piperidine-2,6-dione (187); (3S)-3-(4-(((1-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin- 7-yl)oxy)benzoyl)piperidine-4-carbonyl)piperidin-3-yl)methyl)amino)phenyl)piperidine-2,6- dione (190); 4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)-N-(((1S,4r)-4-(3-(((4-((S)-2,6-dioxopiperidin-3-yl)phenyl)amino)methyl)piperidine- 1-carbonyl)cyclohexyl)methyl)benzamide (191); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4- yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(2-(3-(((4-((S)-2,6-dioxopiperidin-3- yl)phenyl)amino)methyl)piperidin-1-yl)-2-oxoethyl)benzamide (192); 1-(4-((6-bromo-2-(1,3- 556 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-(1-(4-((S)-2,6- dioxopiperidin-3-yl)phenyl)piperidin-3-yl)piperidine-4-carboxamide (193); 4-((6-bromo-2- (1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4-((1-(4- ((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-3-yl)carbamoyl)cyclohexyl)methyl)benzamide (194); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N- (2-((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-3-yl)amino)-2-oxoethyl)benzamide (195); 4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)- N-(3-((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-3-yl)amino)-3- oxopropyl)benzamide (196); 5-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-(1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)piperidin-3-yl)-5-azaspiro[2.3]hexane-1-carboxamide (197); 2-((R)-1-(4-((6- bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)pyrrolidin-3-yl)-N-(1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-3- yl)acetamide (198); 5-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5- b]pyridin-7-yl)oxy)benzoyl)-N-(1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-3-yl)-5- azaspiro[2.3]hexane-1-carboxamide (199); 4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((1S,4r)-4-((1-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)piperidin-3-yl)carbamoyl)cyclohexyl)benzamide (200); (3S)-3-(4-(7-(1-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)piperidine-4-carbonyl)-2,7-diazaspiro[4.5]decan-2-yl)phenyl)piperidine-2,6- dione (201); 4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)-N-(((1S,4r)-4-(2-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2,7-diazaspiro[4.5]decane- 7-carbonyl)cyclohexyl)methyl)benzamide (202); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4- yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(2-(2-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2,7- diazaspiro[4.5]decan-7-yl)-2-oxoethyl)benzamide (203); 4-((6-bromo-2-(1,3-dimethyl-1H- pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-(2-(4-((S)-2,6-dioxopiperidin-3- yl)phenyl)-2,7-diazaspiro[4.5]decan-7-yl)-3-oxopropyl)benzamide (204); (3S)-3-(4-(7-(3-(1- (4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)pyrrolidin-3-yl)propanoyl)-2,7-diazaspiro[4.5]decan-2-yl)phenyl)piperidine- 2,6-dione (205); (3S)-3-(4-(7-(2-((R)-1-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H- imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)pyrrolidin-3-yl)acetyl)-2,7-diazaspiro[4.5]decan-2- yl)phenyl)piperidine-2,6-dione (207); 4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-((1S,4r)-4-(2-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2,7- 557 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT diazaspiro[4.5]decane-7-carbonyl)cyclohexyl)benzamide (208); (3S)-3-(4-(7-(2-((R)-1-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)pyrrolidin-3-yl)acetyl)-2,7-diazaspiro[4.5]decan-2-yl)phenyl)piperidine-2,6- dione (209); 4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)-N-((1S,4r)-4-(2-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2,7-diazaspiro[4.5]decane-7- carbonyl)cyclohexyl)benzamide (210); (3S)-3-(4-(5-(1-(4-((6-bromo-2-(1,3-dimethyl-1H- pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4- carbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (211); 4-((6- bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(((1S,4r)-4- (5-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)octahydropyrrolo[3,4-c]pyrrole-2- carbonyl)cyclohexyl)methyl)benzamide (212); (3S)-3-(4-(5-(3-(1-(4-((6-chloro-2-(1,3- dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)pyrrolidin-3- yl)propanoyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenyl)piperidine-2,6-dione (213); 4- ((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N- (((1S,4r)-4-(2-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2,6-diazaspiro[3.4]octane-6- carbonyl)cyclohexyl)methyl)benzamide (215); (S)-3-(4-(6-(2-((R)-1-(4-((6-bromo-2-(1,3- dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)pyrrolidin-3- yl)acetyl)-2,6-diazaspiro[3.4]octan-2-yl)phenyl)piperidine-2,6-dione (216); (S)-4-((6-bromo- 2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-(6-(4-(2,6- dioxopiperidin-3-yl)phenyl)-2,6-diazaspiro[3.3]heptan-2-yl)-3-oxopropyl)benzamide (217); (3S)-3-(4-(6-(3-(1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin- 7-yl)oxy)benzoyl)pyrrolidin-3-yl)propanoyl)-2,6-diazaspiro[3.3]heptan-2- yl)phenyl)piperidine-2,6-dione (218); (S)-3-(4-(6-(2-((R)-1-(4-((6-bromo-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)pyrrolidin-3-yl)acetyl)-2,6- diazaspiro[3.3]heptan-2-yl)phenyl)piperidine-2,6-dione (219); (S)-3-(4-(6-(2-((R)-1-(4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)pyrrolidin-3-yl)acetyl)-2,6-diazaspiro[3.3]heptan-2-yl)phenyl)piperidine-2,6- dione (220); 4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)-N-((1S,4r)-4-(6-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-2,6-diazaspiro[3.3]heptane- 2-carbonyl)cyclohexyl)benzamide (221); (S)-1-(4-((6-bromo-2-(1,3-dimethyl-1H-pyrazol-4- yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)-N-(1-(4-(2,6-dioxopiperidin-3-yl)phenyl)-4- methylpiperidin-4-yl)piperidine-4-carboxamide (222); (S)-4-((6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(2-((1-(4-(2,6-dioxopiperidin-3- 558 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT yl)phenyl)-4-methylpiperidin-4-yl)amino)-2-oxoethyl)benzamide (223); (S)-4-((6-bromo-2- (1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-(3-((1-(4-(2,6- dioxopiperidin-3-yl)phenyl)-4-methylpiperidin-4-yl)amino)-3-oxopropyl)benzamide (224); 3- (1-(4-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7- yl)oxy)benzoyl)pyrrolidin-3-yl)-N-(1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)-4- methylpiperidin-4-yl)propanamide (225); (S)-3-(4-(4-((1-(1-(4-((6-bromo-2-(1,3-dimethyl- 1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)benzoyl)piperidine-4- carbonyl)piperidin-4-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (235); and 4-((6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-((1r,4r)-4- (4-((1-(4-((S)-2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)piperidine-1- carbonyl)cyclohexyl)benzamide (236).

23. The compound of any one of claims 3, 7, 14, or 15, wherein the compound is selected from the group consisting of (S)-4-((6-chloro-2-(4-(4-(1-((1-(3-(2,6-dioxopiperidin-3- yl)phenyl)piperidin-4-yl)methyl)piperidine-4-carbonyl)piperazin-1-yl)phenyl)-3H- imidazo[4,5-b]pyridin-7-yl)oxy)-N-phenylbenzamide (145); and (R)-4-((6-chloro-2-(4-(4-(1- ((1-(4-(2,6-dioxopiperidin-3-yl)phenyl)piperidin-4-yl)methyl)piperidine-4- carbonyl)piperazin-1-yl)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)oxy)-N-phenylbenzamide (154).

24. The compound of any one of claims 3, 8, 14, or 15, wherein the compound is selected from the group consisting of (S)-3-(3-(4-((4-(4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin- 1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)benzyl)piperazine-1-carbonyl)piperidin-1- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (149); (R)-3-(4-(4-((4-(4-(4-(6-bromo- 7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)benzyl)piperazine-1- carbonyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (158); (S)-3-(4-(4- ((4-((4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2- yl)benzyl)piperazin-1-yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)-2- fluorophenyl)piperidine-2,6-dione (237); (3S)-3-(4-(4-((3-((4-(4-(6-bromo-7-(4-(4- chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)benzyl)piperazin-1- yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)-2-fluorophenyl)piperidine-2,6-dione (238); (S)-3-(4-(4-((4-((4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5- b]pyridin-2-yl)benzyl)piperazin-1-yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)-3- 559 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT fluorophenyl)piperidine-2,6-dione (239); (3S)-3-(4-(4-((3-((4-(4-(6-bromo-7-(4-(4- chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)benzyl)piperazin-1- yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)-3-fluorophenyl)piperidine-2,6-dione (240); (R)-3-(4-(4-((4-((4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5- b]pyridin-2-yl)benzyl)piperazin-1-yl)methyl)piperidin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (241); (3R)-3-(4-(4-((3-((4-(4-(6-bromo-7-(4-(4- chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)benzyl)piperazin-1- yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (242); (R)-3-(4- (4-((4-(4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2- yl)phenyl)piperidine-1-carbonyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6- dione (243); and (R)-3-(4-(4-((4-((4-(4-(6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H- imidazo[4,5-b]pyridin-2-yl)phenyl)piperidin-1-yl)methyl)piperidin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (244).

25. The compound of any one of claims 3, 10, 13, or 15, wherein the compound is selected from the group consisting of 1-[5-(4-{[(3S)-4-(6-{[6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}pyridazin-3-yl)-3-methylpiperazin-1- yl]methyl}piperidin-1-yl)pyridin-2-yl]-1,3-diazinane-2,4-dione (22) and 1-[4-(4-{[(3S)-4-(6- {[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}pyridazin- 3-yl)-3-methylpiperazin-1-yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3-diazinane-2,4-dione (337).

26. The compound of any one of claims 3, 11, 13, or 15, wherein the compound is selected from the group consisting of 1-(5-{4-[(7-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4- yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}-2,3,4,5-tetrahydro-1H-3-benzazepin-3- yl)methyl]piperidin-1-yl}pyridin-2-yl)-1,3-diazinane-2,4-dione (332) and 1-(4-{4-[(7-{[6- chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}-2,3,4,5- tetrahydro-1H-3-benzazepin-3-yl)methyl]piperidin-1-yl}-3-fluorophenyl)-1,3-diazinane-2,4- dione (342).

27. The compound of any one of claims 3, 12, 13, or 15, wherein the compound is selected from the group consisting of 1-[4-(4-{[(3S)-4-(5-{[6-chloro-2-(1,3-dimethyl-1H- pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]oxy}pyrimidin-2-yl)-3-methylpiperazin-1- 560 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT yl]methyl}piperidin-1-yl)-3-fluorophenyl]-1,3-diazinane-2,4-dione (344); 1-[4-(4-{[(3S)-4- (5-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7- yl]oxy}pyrimidin-2-yl)-3-methylpiperazin-1-yl]methyl}piperidin-1-yl)phenyl]-1,3-diazinane- 2,4-dione (348); and (3R)-3-[4-(4-{[(3S)-4-(5-{[6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)- 3H-imidazo[4,5-b]pyridin-7-yl]oxy}pyrimidin-2-yl)-3-methylpiperazin-1- yl]methyl}piperidin-1-yl)phenyl]piperidine-2,6-dione (349).

28. A compound represented by the following formulaa pharmaceutically acceptable salt thereof or stereoisomer thereof, whereinis an unsubstituted or substituted cycloalkyl, heterocycloalkyl, aryl, or heteroaryl wherein one or more substituents are independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen, acyl, amino, -CN, hydroxyl, nitro, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen or alkyl; R1is an unsubstituted or substituted aryl or heteroaryl wherein one or more substituents are independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen, acyl, amino, -CN, hydroxyl, nitro, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen or alkyl; R2is hydrogen or alkyl; X1is an unsubstituted or substituted heterocycloalkylene wherein one or more substituents are independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen, acyl, amino, -CN, hydroxyl, nitro, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen or alkyl; L is a bond or a linker; 561 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCTis a ubiquitin ligase targeting moiety (UTM) having the following chemical formulawherein R3is arylene or heteroarylene; R4is absent or heterocycloalkylene; and R5is absent, alkylene, or -C(O)-.

29. The compound of claim 28, wherein R1is a substituted aryl wherein one or more substituents are independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen; and acyl.

30. The compound of claim 28 or 29, whereinis an unsubstituted or substituted heteroaryl wherein one or more substituents are independently selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen, acyl, amino, -CN, hydroxyl, nitro, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen or alkyl.

31. The compound of any one of claims 28-30, wherein.

32. The compound of any one of claims 28-31, wherein L is a bond.

33. The compound of claim 32, wherein 562 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCTeach R6is independently hydrogen, alkyl, or hydroxyl; X2is -CH2-, oxygen, -NR7-, or sulfur; R7is hydrogen or alkyl; and each n1, n2, and n3 are independently one, two, or three.

35. The compound of any one of claims 28-32 or 34, wherein the compound is selected from the group consisting of (R)-3-(4-(4-((4-(2-((4-(3-chloro-2-fluorobenzoyl)piperazin-1- yl)methyl)-6-(thiazol-2-ylamino)pyridin-4-yl)piperidin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (1), (S)-3-(4-(4-(4-(2-((4-(3-chloro-2- fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2-ylamino)pyridin-4-yl)piperidine-1- carbonyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (4), (R)-3-(4-(4-((4-(2-((4-(3-chloro-2- fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2-ylamino)pyridin-4-yl)piperazin-1- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (5), and (S)-3-(4-(4-(4-(2-((4-(3-chloro- 2-fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2-ylamino)pyridin-4-yl)piperazine-1- carbonyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (8).

36. The compound of any one of claims 28-31, 33, or 34, wherein the compound is selected from the group consisting of (R)-3-(4-(4-((4-((4-(2-((4-(3-chloro-2- 563 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2-ylamino)pyridin-4-yl)piperidin-1- yl)methyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (2); (R)-3-(4-(4- ((4-(4-(2-((4-(3-chloro-2-fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2-ylamino)pyridin- 4-yl)piperidine-1-carbonyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (3); (R)-3-(4-(4-((4-((4-(2-((4-(3-chloro-2-fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2- ylamino)pyridin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)methyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (6); (R)-3-(4-(4-((4-(4-(2-((4-(3-chloro-2- fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2-ylamino)pyridin-4-yl)piperazine-1- carbonyl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (7); (S)-3-(4-(4- (4-((4-(2-((4-(3-chloro-2-fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2-ylamino)pyridin- 4-yl)piperazin-1-yl)methyl)piperidine-1-carbonyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (9); (S)-3-(4-(4-(4-(4-(2-((4-(3-chloro-2-fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2- ylamino)pyridin-4-yl)piperazine-1-carbonyl)piperidine-1-carbonyl)piperidin-1- yl)phenyl)piperidine-2,6-dione (10); (S)-3-(4-(4-(2-(4-(2-((4-(3-chloro-2- fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2-ylamino)pyridin-4-yl)piperazin-1-yl)-2- oxoethyl)-4-hydroxypiperidin-1-yl)phenyl)piperidine-2,6-dione (11); (S)-3-(4-(4-(2-(4-(2-((4- (3-chloro-2-fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2-ylamino)pyridin-4- yl)piperidin-1-yl)-2-oxoethyl)-4-hydroxypiperidin-1-yl)phenyl)piperidine-2,6-dione (12); (S)- 3-(4-(4-(4-(2-((4-(3-chloro-2-fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2- ylamino)pyridin-4-yl)piperazine-1-carbonyl)-4-methylpiperidin-1-yl)phenyl)piperidine-2,6- dione (13); (S)-3-(4-(4-((4-(2-((4-(3-chloro-2-fluorobenzoyl)piperazin-1-yl)methyl)-6- (thiazol-2-ylamino)pyridin-4-yl)piperidin-1-yl)methyl)-4-methylpiperidin-1- yl)phenyl)piperidine-2,6-dione (14); (S)-3-(3-(4-((4-(2-((4-(3-chloro-2- fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2-ylamino)pyridin-4-yl)piperazin-1- yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (15); (S)-3-(6-(4-((4-(2-((4-(3-chloro-2- fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2-ylamino)pyridin-4-yl)piperidin-1- yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione (16); (S)-3-(3-(((1r,4S)-4-((4-(2- ((4-(3-chloro-2-fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2-ylamino)pyridin-4- yl)piperazin-1-yl)methyl)cyclohexyl)oxy)phenyl)piperidine-2,6-dione (17); (S)-3-(3- (((1r,4S)-4-((4-(2-((4-(3-chloro-2-fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2- ylamino)pyridin-4-yl)piperidin-1-yl)methyl)cyclohexyl)oxy)phenyl)piperidine-2,6-dione (18); (S)-3-(5-(4-((4-(2-((4-(3-chloro-2-fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2- ylamino)pyridin-4-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridin-3-yl)piperidine-2,6-dione 564 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT (19); (S)-3-(3-(4-((4-(2-((4-(3-chloro-2-fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2- ylamino)pyridin-4-yl)piperidin-1-yl)methyl)piperidin-1-yl)phenyl)piperidine-2,6-dione (20); and (S)-3-(4-(4-(2-(4-(2-((4-(3-chloro-2-fluorobenzoyl)piperazin-1-yl)methyl)-6-(thiazol-2- ylamino)pyridin-4-yl)piperazin-1-yl)ethyl)-4-hydroxypiperidin-1-yl)phenyl)piperidine-2,6- dione (21).

37. A drug-antibody conjugate comprising an antibody or an antigen binding fragment thereof covalently linked to one or more compounds of any one of claims 1-36.

38. The conjugate of claim 37, wherein the antibody or antigen binding fragment thereof binds to its target with a KD < 30 nM, and the one or more compounds are covalently bound to the antibody or an antigen binding fragment thereof via one or more cleavable linkers.

39. The conjugate of claim 37 or 38, wherein the antibody, or antigen binding fragment thereof, comprises three heavy chain CDRs and three light chain CDRs of an antibody seleted from the group consisting of rituximab, inotuzumab, polatuzumab, trastuzumab, gentuzumab, lintuzumab, and loncastuximab.

40. The conjugate of any one of claims 37-39, wherein the antibody or antigen binding fragment thereof comprises the heavy chain variable region and the light chain variable region of an antibody selected from the group consisting of rituximab, inotuzumab, polatuzumab, trastuzumab, gentuzumab, lintuzumab, and loncastuximab.

41. The conjugate of any one of claims 37-40, wherein the antibody or antigen binding fragment thereof is selected from the group consisting of rituximab, inotuzumab, polatuzumab, trastuzumab, gentuzumab, lintuzumab, and loncastuximab.

42. The conjugate of any one of claims 37-41, that comprises the antigen binding fragment, and wherein the antigen binding fragment is selected from Fv, Fab, Fab’, F(ab’)2Fc, scFv, scFv-Fc, diabodies, triabodies, tetrabodies, minibodies, nanobodies, and combinations thereof.

43. The conjugate of any one of claims 37-42, wherein the antibody or antigen binding fragment thereof is linked to at least one of the compounds of any one of claims 0-29 via one or more linkers. 565 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT 44. The conjugate of claim 43, wherein at least one of the one or more linkers is hydrolytically stable.

45. The conjugate of claim 43, wherein at least one of the one or more linkers is cleavable.

50. The conjugate of claim 45, wherein at least one of the linkers is a protease cleavable linker, an enzyme cleavable linker, a pH-sensitive linker, or a non-cleavable linker.

51. The conjugate of any one of claims 37-50, wherein at least one of the linkers is selected from alkylene, substituted alkylene, heteroalkylene, substituted heteroalkylene, arylene, substituted arylene, heteroarlyene, and substituted heteroarylene.

52. The conjugate of any one of claims 37-50, wherein at least one of the linkers comprises a peptide residue selected from the group consisting of alanine-alanine, valine-citrulline, citrulline-valine, lysine-phenylalanine, phenylalanine-lysine, valine- asparagine, asparagine-valine, threonine-asparagine, asparagine-threonine, serine-asparagine, asparagine-serine, phenylalanine-asparagine, asparagine-phenylalanine, leucine-asparagine, asparagine-leucine, isoleucine-asparagine, asparagine-isoleucine, glycine-asparagine, asparagine-glycine, glutamic acid-asparagine, asparagine-glutamic acid, citrulline-asparagine, asparagine-citrulline, alanine-asparagine, asparagine-alanine, and glycine-glycine-phenylalanine-glycine (GGFG) residues.

53. The conjugate of any one of claims 37-52, wherein at least one of the linkers is conjugated to a native or engineered cysteine residue of the heavy or light chain of the antibody or antigen binding fragment thereof.

54. The conjugate of any one of claims 37-51, wherein the conjugate is represented by the structure of Formula (I) Formula (I) or a pharmaceutically acceptable salt, solvate, stereoisomer, regioisomer, or mixture of regioisomers thereof; wherein Ab is the antibody or antigen-binding fragment thereof; LL is a bond or a linker; 566 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT each PAY is individually one of the compounds of any one of claims 0-29; and n is an integer selected from one to twelve.

55. The conjugate of any one of claims 37-54, represented by Formula (Ia)Formula (Ia) or a pharmaceutically acceptable salt, solvate, stereoisomer, regioisomer, or mixture of regioisomers thereof; wherein Ab is the antibody or antigen-binding fragment thereof; each PAY is individually one of the compounds of any one of claims 0-29; RL is the residue of a reactive group linked to an amino acid of Ab; SP1, SP2, and SP3are, independently at each occurrence, absent or a divalent spacer group; W1is, independently at each occurrence, absentW2is, independently at each occurrence, absent, an amino acid residue, or a peptide residue wherein the amino acid residue or peptide residue is optionally substituted or derivatized with one or more of a HP2group, –N(R)C(O)-(CH2CH2O)bCH3, –N(R)- (CH2CH2O)bCH3, or –C(O)N(R)-(CH2CH2O)bCH3wherein R is hydrogen or –C1-3alkyl; b is an integer from two to twenty-four; HP1is, independently at each occurrence, absent or a divalent hydrophilic group; HP2, when present, is a monovalent hydrophilic group; RT is, independently at each occurrence, absent or a release trigger group; and n is an integer from zero to twelve.

56. The conjugate of claim 55, wherein HP1is absent. 567 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT 57. The conjugate of claim 55, wherein HP1is a hydrophilic polymer.

58. The conjugate of claim 57, wherein HP1is polyethylene glycol (PEG).

59. The conjugate of any one of claims 55-58, wherein HP2is absent.

60. The conjugate of any one of claims 55-58, wherein HP2is a hydrophilic polymer.

61. The conjugate of claim 60, wherein HP2is polyethylene glycol (PEG), –N(R)C(O)-(CH2CH2O)bCH3, –N(R)-(CH2CH2O)bCH3, –C(O)N(R)-(CH2CH2O)bCH3, or methoxypolyethylene glycol (mPEG).

62. The conjugate of any one of claims 55-61, wherein SP1is selected from PAB, PAB- OH, and PABC; or residues thereof.

63. The conjugate of any one of claims 55-61, wherein SP2and SP3are independently absent or selected from –C(H)(CH2NH2)C(O)NH–, -C(O)-, substituted or unsubstituted alkylene, and substituted or unsubstituted heteroalkylene, wherein the substituents are independently selected from -C(O)- and –N(R)C(O)-(CH2CH2O)nCH3, wherein R is hydrogen or –C1-3 alkyl; and n is an integer from two to twenty-four; or a combination thereof.

64. The conjugate of any one of claims 55-63, wherein SP2is absent, -C(O)-, unsubstituted alkylene, alkylene substituted with –N(R)C(O)-(CH2CH2O)nCH3, or a combination thereof.

65. The conjugate of any one of claims 55-64, wherein SP3is absent, –C(H)(CH2NH2)C(O)NH–, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, wherein the substituents are independently selected from -C(O)- and –N(R)C(O)-(CH2CH2O)nCH3, wherein R is hydrogen or –C1-3 alkyl; and n is an integer from two to twenty-four; or 568 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT a combination thereof.

66. The conjugate of any one of claims 55-64, wherein W2is independently an amino acid residue or a peptide residue wherein the amino acid residue or the peptide residue is optionally substituted or derivatized with a HP2or –N(R)-(CH2CH2O)bCH3, or a combination thereof.

67. The conjugate of claim 66, wherein W2is selected from valine-citrulline, valine- alanine, alanine-alanine, alanine-phenylalanine, phenylalanine-lysine, glycine-valine-citrulline, and glycine-glycine-glycine, glutamic acid-valine-citrulline, aspartic acid-valine-citrulline, glutamic acid-valine-alanine, aspartic acid-valine-alanine, glycine-glycine-phenylalanine-glycine (GGFG), –NH-C(H)(CH2C(O)N(R)-(CH2CH2O)bCH3)C(O)-valine-citrulline, –NH-C(H)(CH2CH2C(O)N(R)-(CH2CH2O)bCH3)C(O)-valine-citrulline, –NH-C(H)(CH2C(O)N(R)-(CH2CH2O)bCH3)C(O)-valine-alanine, and –NH-C(H)(CH2CH2C(O)N(R)-(CH2CH2O)bCH3)C(O)-valine-alanine.

68. The conjugate of any one of claims 55-67, wherein RT is a β-glucuronidase-cleavable β-glucuronide.

69. The conjugate of any one of claims 55-68, wherein RL is linked to the side chain of a residue of Ab selected from cysteine residues, glutamine residues, lysine residues, and amino- terminal residues.

70. The conjugate of any one of claims 55-69, wherein RL is an amide moiety, the residue of a maleimide moiety, or a succinimde moiety.

71. A linker-payload represented by Formula (II) Formula (II) or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein PAY is a compound of any one of claims 0-29; RL is a reactive group; SP1, SP2, and SP3are, independently at each occurrence, absent or a divalent spacer group; 569 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT W1is, independently at each occurrence, absentW2is, independently at each occurrence, absent, an amino acid residue, or a peptide residue wherein the amino acid residue or peptide residue is optionally substituted or derivatized with one or more of a HP2group, –N(R)C(O)-(CH2CH2O)bCH3, –N(R)-(CH2CH2O)bCH3, or –C(O)N(R)-(CH2CH2O)bCH3 wherein R is hydrogen or –C1-3 alkyl; b is an integer from two to twenty-four; HP1is, independently at each occurrence, absent or a divalent hydrophilic group; HP2, when present, is a monovalent hydrophilic group; and RT is independently, at each occurrence, absent or a release trigger group.

72. The linker-payload of claim 71, wherein HP1is absent.

73. The linker-paylaod of claim 71, wherein HP1is a hydrophilic polymer.

74. The linker-payload of claim 73, wherein HP1is polyethylene glycol (PEG).

75. The linker-payload of any one of claims 71-74, wherein HP2is absent.

76. The linker-payload of any one of claims 71-74, wherein HP2is a hydrophilic polymer.

77. The linker-payload of claim 76, wherein HP2is polyethylene glycol (PEG), –N(R)C(O)-(CH2CH2O)bCH3, –N(R)-(CH2CH2O)bCH3, –C(O)N(R)-(CH2CH2O)bCH3, or methoxypolyethylene glycol (mPEG).

78. The linker-payload of any one of claims 71-77, wherein SP1is selected from PAB, PAB-OH, and PABC; or residues thereof.

79. The linker-payload of any one of claims 71-77, wherein SP2and SP3are independently absent or selected from –C(H)(CH2NH2)C(O)NH–, -C(O)-, substituted or unsubstituted alkylene, and substituted or unsubstituted heteroalkylene, wherein the substituents are independently selected from -C(O)- and –N(R)C(O)-(CH2CH2O)nCH3, wherein 570 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT R is hydrogen or –C1-3 alkyl; and n is an integer from two to twenty-four; or a combination thereof.

80. The linker-payload of any one of claims 71-79, wherein SP2is absent, -C(O)-, or unsubstituted alkylene, alkylene substituted with –N(R)C(O)-(CH2CH2O)nCH3, or a combination thereof.

81. The linker-payload of any one of claims 71-80, wherein SP3is absent, –C(H)(CH2NH2)C(O)NH–, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, wherein the substituents are independently selected from -C(O)- and –N(R)C(O)-(CH2CH2O)nCH3, wherein R is hydrogen or –C1-3 alkyl; and n is an integer from two to twenty-four; or a combination thereof.

82. The linker-payload of any one of claims 71-80, wherein W2is independently an amino acid residue or a peptide residue wherein the amino acid residue or the peptide residue is optionally substituted or derivatized with a HP2or –N(R)-(CH2CH2O)bCH3, or a combination thereof.

83. The linker-payload of claim 82, wherein W2is selected from valine-citrulline, valine-alanine, alanine-alanine, alanine-phenylalanine, phenylalanine-lysine, glycine-valine-citrulline, glycine-glycine-glycine, glutamic acid-valine-citrulline, aspartic acid-valine-citrulline, glutamic acid-valine-alanine, aspartic acid-valine-alanine, glycine-glycine-phenylalanine-glycine (GGFG), –NH-C(H)(CH2C(O)N(R)-(CH2CH2O)bCH3)C(O)-valine-citrulline, –NH-C(H)(CH2CH2C(O)N(R)-(CH2CH2O)bCH3)C(O)-valine-citrulline, –NH-C(H)(CH2C(O)N(R)-(CH2CH2O)bCH3)C(O)-valine-alanine, and –NH-C(H)(CH2CH2C(O)N(R)-(CH2CH2O)bCH3)C(O)-valine-alanine. 571 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT 84. The linker-payload of any one of claims 71-83, wherein RT is a β-glucuronidase- cleavable β-glucuronide.

85. The linker-payload of any one of claims 71-84, wherein RL is an amide moiety, a maleimide moiety, or an N-hydroxysuccinimde moiety.

86. The conjugate or linker-payload of any one of claims 55-85, wherein at least one payload is a residue of Formula A, B, C, D, E, F, G, or H572 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCTa pharmaceutically acceptable salt thereof or stereoisomer thereof, wherein R1is, independently, hydrogen or halogen;R3is hydrogen or alkyl; X1is halogen; X2is -N(H)-, oxygen, or sulfur; X3is alkylene; heteroalkylene; cycloalkylene; arylene; heteroarylene; unsubstituted or substituted heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, haloalkyl, halogen, acyl, amino, -CN, hydroxyl, nitro, -C(O)-, -SO2-, hydroxyalkyl, alkoxyalkyl, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen, alkyl, or alkenyl; unsubstituted or substituted -S(O)2-heterocycloalkylene wherein one or more substituents are selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl, halogen, acyl, amino, -CN, hydroxyl, nitro, hydroxyalkyl, -C(O)-, 573 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT alkoxyalkyl, -COOR100, -C(O)R101, and -SO3R102wherein R100, R101, and R102are, independently, hydrogen, alkyl, or alkenyl;; ; -C(O)-; -C(O)N(H)-; -N(H)-; -O-; or -S(O)2-; X4is carbon or nitrogen, wherein when X4is nitrogen then the R1bound to X4is absent; L is a bond or a linker;is a ubiquitin ligase targeting moiety (UTM); and each n is independently zero, one, or two. . The conjugate or linker-payload of claim 86, whereinis a ubiquitin ligase targeting moiety (UTM) having the following chemical formulawherein X5is carbon or nitrogen; R4is absent, -N(R4a)-, oxygen, sulfur, or -N(R4a)C(O)- wherein R4ais hydrogen or alkyl; R5is unsubstituted or substituted arylene or heteroarylene wherein one or more substituents are independently selected from the group consisting of halogen and alkyl; R6is absent, -N(R6a)-, oxygen, or sulfur wherein R6ais hydrogen or alkyl; R7is absent; unsubstituted or substituted cycloalkylene or heterocycloalkylene wherein one or more substituents are independently selected from the group consisting of halogen and alkyl; an unsubstituted or substituted five- to fifteen-membered spiro heterocycloalkylene; or an unsubstituted or substituted four- to fourteen-membered fused heterocycloalkylene; and R8is absent, alkylene, -C(O)-, -N(R8a)-, oxygen, or sulfur wherein R8ais hydrogen or alkyl. 574 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT 88. The compound of claim 54, wherein LL is a bond.

89. The compound of claim 54, wherein LL is a linker.

90. The conjugate or linker-payload of any of claims 86-89, whereinis selected from , , , ,, , 575 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT576 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT91. The conjugate or linker-payload of any one of claims 86-90, according to Formula J, K, L, M, N, O, P, Q, R, S, T, U, V, W, X, or YFormula J, 577 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCTFormula N, 578 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT579 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT580 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCTor a pharmaceutically acceptable salt thereof.

92. The conjugate or linker-payload of any one of claims 86-91, wherein L is selected from the group consisting of581 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT582 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT583 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT584 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCTwherein each n1 is independently one, two, or three; each n2 is independently one, two, or three; each n3 is independently an integer from one to ten; each R9is independently hydrogen or alkyl; each R10is independently alkyl; R11is hydrogen, alkyl, hydroxymethyl, or haloalkyl; R12is hydrogen, an amino acid side chain, or R9is further bonded to R12to form proline; X6is NR9, oxygen, or sulfur; each X7is independently carbon or nitrogen; and aa is an integer from one to five.

93. The conjugate or linker-payload of claim 86 or 87, wherein at least one payload or compound of any one of claims 1-36 is a compound in Table 1 or a pharmaceutically acceptable salt thereof.

94. A pharmaceutical composition comprising an effective amount of a compound of any one of claims 1, 28, or 37 in combination with a pharmaceutically acceptable carrier, additive, or excipient; and optionally in further combination with an additional biologically active agent.

95. A method of treating cancer in a patient in need thereof, wherein dysregulated protein activity is responsible for the cancer, the method comprising administering to the patient an effective amount of the compound of any one of claims 1, 28, or 37, or the pharmaceutical composition of claim 94, wherein the compound modulates the amount or activity of the 585 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT protein in the patient, wherein the cancer is selected from squamous-cell carcinoma, basal cell carcinoma, adenocarcinoma, hepatocellular carcinomas, and renal cell carcinomas, cancer of the bladder, bowel, breast, cervix, colon, esophagus, head, kidney, liver, lung, neck, ovary, pancreas, prostate, and stomach; leukemias; benign and malignant lymphomas, particularly Burkitt's lymphoma and Non-Hodgkin's lymphoma; benign and malignant melanomas; myeloproliferative diseases; sarcomas, including Ewing's sarcoma, hemangiosarcoma, Kaposi's sarcoma, liposarcoma, myosarcomas, peripheral neuroepithelioma, synovial sarcoma, gliomas, astrocytomas, oligodendrogliomas, ependymomas, gliobastomas, neuroblastomas, ganglioneuromas, gangliogliomas, medulloblastomas, pineal cell tumors, meningiomas, meningeal sarcomas, neurofibromas, and Schwannomas; bowel cancer, breast cancer, prostate cancer, cervical cancer, uterine cancer, lung cancer, ovarian cancer, testicular cancer, thyroid cancer, astrocytoma, esophageal cancer, pancreatic cancer, stomach cancer, liver cancer, colon cancer, melanoma; carcinosarcoma, Hodgkin's disease, Wilms' tumor or teratocarcinomas. T-lineage Acute lymphoblastic Leukemia (T-ALL), T-lineage lymphoblastic Lymphoma (T-LL), Peripheral T-cell lymphoma, Adult T-cell Leukemia, Pre-B ALL, Pre-B Lymphomas, Large B-cell Lymphoma, Burkitts Lymphoma, B-cell ALL, Philadelphia chromosome positive ALL, Philadelphia chromosome positive CML, prostate cancer, Kennedy's Disease, Lymphoma, diabetes, diabetes mellitus type I, diabetes mellitus type II, obesity, colorectal cancer, head & neck cancer, immune system disorders, leukemia, stem cell growth, stem cell transplantation, wound healing, atherosclerosis, endometrial cancer, McCune-Albright Syndrome, acute lymphoblastic leukemia, multiple myeloma myeloproliferative diseases, and B cell Lymphoma.

96. The method of claim 95, wherein the cancer being treated is selected from breast cancer, colorectal cancer, hepatocellular carcinoma, cervical cancer, laryngeal cancer, leukemia, lymphoma, lung cancer, multiple myeloma, neuroblastoma, ovarian cancer, prostate cancer, and sarcoma, and wherein the dysregulated protein is Aurora A or MYC.

97. A method of treating a solid tumor in a subject in need thereof, the tumor being characterized by an elevated Aurora A expression or dependence as determined by an IHC score ≥ 2+ or proteomic quantification exceeding two-fold over matched normal tissue, comprising administering to the subject a therapeutically effective amount of the compound 586 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT of any one of claims 1, 28, or 37, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 94.

98. The method of claim 95 or 97, wherein the compound reduces levels of Aurora A kinase in tumor cells as determined by an IHC score ≥ 2+.

99. The method of claim 95 or 37, wherein the compound reduces levels of phosphorylated Aurora A in tumor cells as determined by an IHC score ≥ 2+.

100. The method of any one of claims 95, 97, or 98, wherein the tumor is selected from the group consisting of a neuroblastoma, medulloblastoma (Group 2 or Group 3), small cell lung cancer, glioblastoma, retinoblastoma, prostate cancer with neuroendocrine features (NEPC subtype), Wilms tumor, triple-negative breast cancer, colorectal cancer, high-grade serous ovarian cancer, and Ewing sarcoma.

101. The method of any one of claims 95 or 97-100, wherein the compound achieves a brain-to-plasma or brain:plasma unbound concentration ratio of at least four and wherein the tumor is glioblastoma or medulloblastoma.

102. The method of any one of claims 95 or 97-101, wherein treatment results in at least a 50% reduction in Aurora A protein levels in tumor cells within one day of administration, as measured by immunoblot or quantitative proteomic assay.

103. The method of any one of claims 95 or 97-101, wherein the compound induces ≥ 70% degradation of Aurora A in 293T cells within six hours at 100 nM as measured by HiBiT assay.

104. The method of any one of claims 95 or 97-101, wherein the subject has a tumor exhibiting Aurora A overexpression as determined by an IHC score ≥ 2+ or proteomic quantification exceeding two-fold over matched normal tissue.

105. A method of treating a tumor in a subject in need thereof, the tumor being characterized by NMYC amplification or dependence, comprising administering to the 587 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT subject a therapeutically effective amount of the compound of any one of claims 1, 28, or 37, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 94, wherein the compound reduces levels of both Aurora A and NMYC proteins in tumor cells.

106. The method of claim 95 or 105, wherein the tumor is neuroblastoma with NMYC amplification, and treatment results in at least a 30% reduction in NMYC protein levels in tumor cells within 72 hours, as measured by immunoblot or quantitative proteomic assay.

107. The method of claim 95 or 105, wherein the tumor is small cell lung cancer with NMYC amplification, and the compound induces reduction of protein levels of both Aurora A and NMYC proteins in tumor cells.

108. The method of claim 95 or 105, wherein the tumor is neuroendocrine prostate cancer (NEPC subtype) exhibiting NMYC overexpression, and treatment results in measurable reduction of both NMYC and Aurora A proteins in tumor cells.

109. A method of treating cancer comprising administering to a patient in need thereof an effective amount of the compound of any one of claims 1, 28, or 37, or the pharmaceutical composition of claim 94, in combination with an additional therapeutic agent.

110. The method of claim 109, wherein the additional therapeutic agent is a chemotherapeutic or antineoplastic agent.

111. The method of claim 109, wherein the chemotherapeutic or antineoplastic agent is selected from the group consisting of alkylating agents including nitrogen mustard analogues, further including cyclophosphamide, chlorambucil, melphalan, chlormethine, ifosfamide, trofosfamide, prednimustine, bendamustine, and melphalan flufenamide, alkylsulfonates, further including busulfan, treosulfan, and mannosulfan, ethylene imines, further including thiotepa, triaziquone, and carboquone, nitrosoureas, further including carmustine, lomustine, semustine, streptozocin, fotemustine, nimustine, ranimustine, and uramustine, epoxides, further including etoglucid, other alkylating agents, further including mitobronitol, pipobroman, temozolomide, and dacarbazine; antimetabolites including folic acid analogues, further including methotrexate, raltitrexed, pemetrexed, and pralatrexate, purine analogues, 588 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT further including mercaptopurine, tioguanine, cladribine, fludarabine, clofarabine, nelarabine, and rabacfosadine, pyrimidine analogues, further including cytarabine, fluorouracil, tegafur, carmofur, gemcitabine, capecitabine, azacitidine, decitabine, floxuridine, and trifluridine, plant alkaloids and other natural products including vinca alkaloids and analogues, further including vinblastine, vincristine, vindesine, vinorelbine, vinflunine, and vintafolide, podophyllotoxin derivatives, further including etoposide, and teniposide, colchicine derivatives, further including demecolcine, taxanes, further including paclitaxel, docetaxel, paclitaxel poliglumex, cabazitaxel, and paclitaxel and encequidar, topoisomerase 1 (TOP1) inhibitors, further including topotecan, irinotecan, etirinotecan pegol, and belotecan, other plant alkaloids and natural products, further including trabectedin, cytotoxic antibiotics and related substances including actinomycines, further including dactinomycin, anthracyclines and related substances, further including doxorubicin, daunorubicin, epirubicin, aclarubicin, zorubicin, idarubicin, mitoxantrone, pirarubicin, valrubicin, amrubicin, and pixantrone, other cytotoxic antibiotics, further including bleomycin, plicamycin, mitomycin, ixabepilone, and utidelone, protein kinase inhibitors including BCR-ABL tyrosine kinase inhibitors, further including imatinib, dasatinib, nilotinib, bosutinib, ponatinib, and asciminib, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, further including gefitinib, erlotinib, afatinib, osimertinib, rociletinib, olmutinib, dacomitinib, icotinib, lazertinib, mobocertinib, and aumolertinib, B- Raf serine-threonine kinase (BRAF) inhibitors, further including vemurafenib, dabrafenib, and encorafenib, anaplastic lymphoma kinase (ALK) inhibitors, further including crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib, mitogen-activated protein kinase (MEK) inhibitors, further including trametinib, cobimetinib, binimetinib, selumetinib, and mirdametinib, cyclin-dependent kinase (CDK) inhibitors, further including palbociclib, ribociclib, and abemaciclib, mammalian target of rapamycin (mTOR) kinase inhibitors, further including temsirolimus, everolimus, ridaforolimus, and sirolimus, human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors, further including lapatinib, neratinib, and tucatinib, Janus-associated kinase (JAK) inhibitors, further including ruxolitinib, fedratinib, pacritinib, and momelotinib, vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors, further including axitinib, cediranib, tivozanib, and fruquintinib, Bruton's tyrosine kinase (BTK) inhibitors, further including ibrutinib, acalabrutinib, zanubrutinib, orelabrutinib, pirtobrutinib, and tirabrutinib, 589 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT phosphatidylinositol-3-kinase (Pi3K) inhibitors, further including idelalisib, copanlisib, alpelisib, duvelisib, and parsaclisib, fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors, further including erdafitinib, pemigatinib, infigratinib, and futibatinib, other protein kinase inhibitors, further including sunitinib, sorafenib, pazopanib, vandetanib, regorafenib, masitinib, cabozantinib, lenvatinib, nintedanib, midostaurin, quizartinib, larotrectinib, gilteritinib, entrectinib, pexidartinib, capmatinib, avapritinib, ripretinib, tepotinib, selpercatinib, pralsetinib, surufatinib, umbralisib, sitravatinib, capivasertib, repotrectinib, and toceranib, monoclonal antibodies and antibody-drug conjugates including clusters of differentiation 20 (CD20) inhibitors, further including rituximab, ofatumumab, and obinutuzumab, clusters of differentiation 22 (CD22) inhibitors, further including inotuzumab ozogamicin, and moxetumomab pasudotox, clusters of differentiation 38 (CD38) inhibitors, further including daratumumab, and isatuximab, human epidermal growth factor receptor 2 (HER2) inhibitors, further including trastuzumab, pertuzumab, trastuzumab emtansine, trastuzumab deruxtecan, trastuzumab duocarmazine, margetuximab, and zanidatamab, epidermal growth factor receptor (EGFR) inhibitors, further including cetuximab, panitumumab, and necitumumab, programmed cell death protein 1 / death ligand 1 (PD-1 / PDL-1) inhibitors, further including nivolumab, pembrolizumab, durvalumab, avelumab, atezolizumab, cemiplimab, dostarlimab, prolgolimab, tislelizumab, retifanlimab, sugemalimab, serplulimab, and toripalimab, vascular endothelial growth factor (VEGF / VEGFR) inhibitors, further including bevacizumab, and ramucirumab, other monoclonal antibodies and antibody-drug conjugates, further including edrecolomab, gemtuzumab ozogamicin, catumaxomab, ipilimumab, brentuximab vedotin, dinutuximab beta, blinatumomab, elotuzumab, mogamulizumab, olaratumab, bermekimab, tafasitamab, enfortumab vedotin, polatuzumab vedotin, belantamab mafodotin,oportuzumab monatox, Sacituzumab govitecan, amivantamab, sabatolimab, tremelimumab, naxitamab,loncastuximab tesirine, tisotumab vedotin, teclistamab, mosunetuzumab, mirvetuximab soravtansine, epcoritamab, glofitamab, talquetamab, zolbetuximab, elranatamab, tarlatamab, odronextamab, datopotamab deruxtecan, and patritumab deruxtecan, combinations of monoclonal antibodies and antibody-drug conjugates, further including pertuzumab and trastuzumab, nivolumab and relatlimab, and prolgolimab and nurulimab, other antineoplastic agents including platinum compounds, further including cisplatin, carboplatin, oxaliplatin, satraplatin, and polyplatillen, methylhydrazines further including, procarbazine, sensitizers used in photodynamic / radiation therapy, further including porfimer 590 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT sodium, methyl aminolevulinate, aminolevulinic acid, temoporfin, efaproxiral, and padeliporfin, retinoids for cancer treatment, further including tretinoin, alitretinoin, and bexarotene, proteasome inhibitors, further including bortezomib, carfilzomib, and ixazomib, histone deacetylase (HDAC) inhibitors, further including vorinostat, romidepsin, panobinostat, belinostat, entinostat, tucidinostat, and resminostat, Hedgehog pathway inhibitors, further including vismodegib, sonidegib, and glasdegib, poly (ADP-ribose) polymerase (PARP) inhibitors, further including olaparib, niraparib, rucaparib, talazoparib, veliparib, pamiparib, and niraparib and abiraterone, antineoplastic cell and gene therapy, further including sitimagene ceradenovec, talimogene laherparepvec, axicabtagene ciloleucel, tisagenlecleucel, ciltacabtagene autoleucel, brexucabtagene autoleucel, idecabtagene vicleucel, lisocabtagene maraleucel, tabelecleucel, nadofaragene firadenovec, lifileucel, and obecabtagene autoleucel, isocitrate dehydrogenase (IDH) inhibitors, further including enasidenib, ivosidenib, olutasidenib, and vorasidenib, other antineoplastic agents, further including amsacrine, asparaginase, altretamine, hydroxycarbamide, lonidamine, pentostatin, masoprocol, estramustine, mitoguazone, tiazofurine, mitotane, pegaspargase, arsenic trioxide, denileukin diftitox, celecoxib, anagrelide, oblimersen, omacetaxine mepesuccinate, eribulin, aflibercept, olaparib, venetoclax, vosaroxin, plitidepsin, epacadostat, selinexor, tagraxofusp, lurbinectedin, tazemetostat, sotorasib, belzutifan, tebentafusp, adagrasib, navitoclax, eflornithine, imetelstat, nirogacestat, darinaparsin, para-toluenesulfonamide, pelabresib, idroxioleic acid, calaspargase pegol, tigilanol tiglate, and verdinexor, combinations of antineoplastic agents, further including cytarabine and daunorubicin, and bifikafusp alfa and onfekafusp alfa, “7+3” chemotherapy or regimen, and combinations thereof, and the like.

112. The method of claim 109 or 111, wherein the chemotherapeutic or antineoplastic agent is selected from the group consisting of paclitaxel, docetaxel, rituximab, vincristine, bortezomib, irinotecan and temozolomide, cytarabine, daunorubicin and cytarabine (“7+3” chemotherapy or regimen), osimertinib, topotecan, venetoclax, and cyclophosphamide.

113. The method of claim 109, wherein the additional therapeutic agent is an immunotherapeutic agent or immune therapy.

114. The composition of claim 94, wherein the composition is administered orally or intravenous. 591 1104745337\13\AMERICASAttorney Docket No.121843.00323 NU-3800 PCT 115. The composition of claim 94 or 114, wherein the composition is dosed daily or weekly.

116. The method of claim 95, wherein the cancer is taxane-refractory, platinum-refractory, or checkpoint-refractory. 592 1104745337\13\AMERICAS

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