WO2025199151A1 - Small molecule cereblon binders that induce the degradation of proteins (kdm4b, vcl) relevant to cancer - Google Patents

Abstract

The present disclosure relates to compounds and compositions, and methods of uing the compounds and compositions for inducing the degradation of proteins that are relevant to cancer such as. for example. KDM4B and VCL. Also described are methods of treating cancer (e.g, a sarcoma, a carcinoma, a hematological cancer, a solid tumor, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, non-small cell lung carcinoma, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, melanoma, glioma, leukemia, lymphoma, chronic myeloproliferative disorder, myelodysplastic syndrome, myeloproliferative neoplasm, plasma cell neoplasm (myeloma)) using the disclosed compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

Description

SMALL MOLECULE CEREBLON BINDERS THAT INDUCE THE DEGRADATION OF PROTEINS (KDM4B, VCL) RELEVANT TO CANCER CROSS-REFERENCE TO RELATED APPLICATIONS This Application claims the benefit of U.S. Provisional Application No.63/567,094, filed on March 19, 2024, the contents of which are incorporated herein by reference in their entireity. BACKGROUND Overexpression of KDM4 proteins is prevalent in various cancers, including breast (Patani N; et. al., (2011) Anticancer Res., 31 (12), 4115–4125), prostate (Cloos PAC; et. al., 2006 Nature, 442 (7100), 307–311), colorectal (Berry WL; Janknecht R, (2013) Cancer Res. , 73 (10), 2936–2942), lung (Jie X; et al., (2021) Cell Death Differ, 28 (7), 2095–2111), blood (Boila LD; et al., (2018) Exp. Hematol , 58, 44–51.e47), neuroblastoma (Yang J; et al., (2015) J. Natl. Cancer Inst , 107 (6), djv080), malignant pleural mesothelioma (Lapidot M; et al., (2021) Br. J. Cancer , 125 (4), 582–592), and other cancers. Genetic depletion or pharmacologic inhibition of KDM4 has an anticancer effect (Yang J; et al., (2015) J. Natl. Cancer Inst, 107 (6), djv080; Metzger E; et. al., (2017) Cancer Res., 77 (21), 5900–5912), making KDM4 an attractive target for the development of therapeutics that modulate the activity of KDM4 proteins. Vinculin (VCL), a membrane-cytoskeletal protein, is significantly upregulated in pancreatic cancer tissues and has been identified as a biomarker for pancreatic cancer (Wang, Yufeng, et al. (2012) Oncology reports 28.51845-1850; Islam, S.; et al. (2021) Anticancer Research October 41 (10) 4979-4984). The underlying mechanisms of VCL in pancreatic cancer is still underdetermined. However, enhanced proliferation activity has been observed in vinculin-expressing samples and it has been proposed that VCL has a role in promoting proliferation (Ruiz C, et al., (2011) J Pathol. Mar;223(4):543-52). Several small molecule KDM4 inhibitors with different chemotypes have been reported; however, only one selective and potent KDM4 inhibitor has entered phase 1 clinical trials (TACH101), and TACH101 is currently being evaluated for the treatment of gastrointestinal and high microsatellite instability (MSI-H) metastatic colorectal cancers (https://ClinicalTrials.gov/show/NCT05076552. (accessed 2022-03-29)). To date, no inhibitors of VCL have been reported. As an alternative therapeutic modality to protein inhibition, ubiquitin-dependent proteolysis is a major pathway that degrades intracellular proteins as part of normal cellular maintenance processes has emerged as an attractive strategy to induce selective protein degradation. Compounds composed of a ligand recognizing selected proteins and a ligand recognizing an E3 ubiquitin ligase (e.g., cereblon) induce proteasome-mediated degradation of selected proteins via their recruitment to the E3 ubiquitin ligase and subsequent ubiquitination. These drug-like molecules offer the possibility of temporal control over protein expression. Such compounds are capable of inducing the inactivation of a protein of interest upon addition to cells or administration to an animal or human, and could lead to a new paradigm for the treatment of diseases by removing pathogenic or oncogenic proteins (Crews C, Chemistry & Biology, 2010, l7(6):551-555; Schneekloth JS Jr., Chembiochem, 2005, 6(l):40-46). Despite the significant interest in small molecule protein degraders, the successful development of such molecules for therapeutic cancer treatments has remained elusive. Thus, there remain a need for small molecules that leverage E3 ligase mediated protein degradation to target cancer-associated proteins such as KDM4 and VCL. SUMMARY In accordance with the purpose(s) of the invention, as embodied and broadly described herein, the invention, in one aspect, relates to compounds, compositions, and methods for inducing the degradation of proteins (e.g., KDM4B, VCL) that are relevant to cancer. The disclosed compounds and compositions can be useful in the treatment of a variety of different cancers including, but not limited to, a sarcoma, a carcinoma, a hematological cancer, a solid tumor, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, non-small cell lung carcinoma, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, melanoma, glioma, leukemia, lymphoma, chronic myeloproliferative disorder, myelodysplastic syndrome, myeloproliferative neoplasm, and plasma cell neoplasm (myeloma). Thus, disclosed are compounds having a structure represented by a formula: , wherein m is selected from 0 and 1; wherein A is selected from ‒SO2‒ and ‒C(O)‒; and wherein Cy¹ is selected from a C3-C10 cycloalkyl, a C2-C9 heterocycloalkyl, a C6-C10 aryl, and a C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1- C4 alkyl), and Cy²; wherein R¹⁰ is selected from hydrogen and C1-C4 alkyl; and wherein Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒ CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, or a pharmaceutically acceptable salt thereof. Also disclosed are pharmaceutical compositions comprising an effective amount of a disclosed compound, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. Also disclosed are methods of degrading a target protein in a cell in need thereof, the method comprising contacting the cell with an effective amount of a disclosed compound, or a pharmaceutically acceptable salt thereof. Also disclosed are methods of degrading a target protein in a subject, the method comprising administering to the subject an effective amount of a disclosed compound, or a pharmaceutically acceptable salt thereof. Also disclosed are methods of treating a cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of a disclosed compound, or a pharmaceutically acceptable salt thereof. Also disclosed are kits comprising a disclosed compound or a pharmaceutically acceptable salt thereof, and one or more of: (a) an agent known to treat a cancer; (b) instructions for administering the compound in connection with treating a cancer; and (c) instructions for treating a cancer. While aspects of the present invention can be described and claimed in a particular statutory class, such as the system statutory class, this is for convenience only and one of skill in the art will understand that each aspect of the present invention can be described and claimed in any statutory class. Unless otherwise expressly stated, it is in no way intended that any method or aspect set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not specifically state in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including matters of logic with respect to arrangement of steps or operational flow, plain meaning derived from grammatical organization or punctuation, or the number or type of aspects described in the specification. BRIEF DESCRIPTION OF THE DRAWINGS The accompanying figures, which are incorporated in and constitute a part of this specification, illustrate several aspects and together with the description serve to explain the principles of the invention. FIG.1 shows representative immunoblots for KDM4B protein degradation after the treatment of BE2C cells with molecular glue compounds. FIG.2A-C show representative immunoblots for KDM4B degradation by compound 6. FIG.3A and FIG.3B show representative immunoblots for KDM4B degradation in multiple cell lines. FIG.4A-C show representative immunoblots for VCL degradation by compound 5. FIG.5 shows representative immunoblots for VCL protein degradation. While aspects of the present invention can be described and claimed in a particular statutory class, such as the system statutory class, this is for convenience only and one of skill in the art will understand that each aspect of the present invention can be described and claimed in any statutory class. Unless otherwise expressly stated, it is in no way intended that any method or aspect set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not specifically state in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including matters of logic with respect to arrangement of steps or operational flow, plain meaning derived from grammatical organization or punctuation, or the number or type of aspects described in the specification. DETAILED DESCRIPTION The present invention can be understood more readily by reference to the following detailed description of the invention and the Examples included therein. Before the present compounds, compositions, articles, systems, devices, and/or methods are disclosed and described, it is to be understood that they are not limited to specific synthetic methods unless otherwise specified, or to particular reagents unless otherwise specified, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, example methods and materials are now described. While aspects of this disclosure can be described and claimed in a particular statutory class, such as the system statutory class, this is for convenience only and one of skill in the art will understand that each aspect of this disclosure can be described and claimed in any statutory class. Unless otherwise expressly stated, it is in no way intended that any method or aspect set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not specifically state in the claims or description that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including matters of logic with respect to arrangement of steps or operational flow, plain meaning derived from grammatical organization or punctuation, or the number or type of aspects described in the specification. Throughout this application, various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this pertains. The references disclosed are also individually and specifically incorporated by reference herein for the material contained in them that is discussed in the sentence in which the reference is relied upon. Nothing herein is to be construed as an admission that the present application is not entitled to antedate such publication by virtue of prior invention. Further, stated publication dates may be different from actual publication dates, which can require independent confirmation. A. DEFINITIONS As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a functional group,” “an alkyl,” or “a residue” includes mixtures of two or more such functional groups, alkyls, or residues, and the like. As used in the specification and in the claims, the term “comprising” can include the aspects “consisting of” and “consisting essentially of.” Ranges can be expressed herein as from “about” one particular value, and/or to “about” another particular value. When such a range is expressed, another aspect includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed. As used herein, the terms “about” and “at or about” mean that the amount or value in question can be the value designated some other value approximately or about the same. It is generally understood, as used herein, that it is the nominal value indicated ±10% variation unless otherwise indicated or inferred. The term is intended to convey that similar values promote equivalent results or effects recited in the claims. That is, it is understood that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but can be approximate and/or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art. In general, an amount, size, formulation, parameter or other quantity or characteristic is “about” or “approximate” whether or not expressly stated to be such. It is understood that where “about” is used before a quantitative value, the parameter also includes the specific quantitative value itself, unless specifically stated otherwise. References in the specification and concluding claims to parts by weight of a particular element or component in a composition denotes the weight relationship between the element or component and any other elements or components in the composition or article for which a part by weight is expressed. Thus, in a compound containing 2 parts by weight of component X and 5 parts by weight component Y, X and Y are present at a weight ratio of 2:5, and are present in such ratio regardless of whether additional components are contained in the compound. A weight percent (wt. %) of a component, unless specifically stated to the contrary, is based on the total weight of the formulation or composition in which the component is included. As used herein, the terms “optional” or “optionally” means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where said event or circumstance occurs and instances where it does not. As used herein, the term “subject” can be a vertebrate, such as a mammal, a fish, a bird, a reptile, or an amphibian. Thus, the subject of the herein disclosed methods can be a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig, or rodent. The term does not denote a particular age or sex. Thus, adult and newborn subjects, as well as fetuses, whether male or female, are intended to be covered. In one aspect, the subject is a mammal. A patient refers to a subject afflicted with a disease or disorder. The term “patient” includes human and veterinary subjects. As used herein, the term “treatment” refers to the medical management of a patient with the intent to cure, ameliorate, stabilize, or prevent a disease, pathological condition, or disorder. This term includes active treatment, that is, treatment directed specifically toward the improvement of a disease, pathological condition, or disorder, and also includes causal treatment, that is, treatment directed toward removal of the cause of the associated disease, pathological condition, or disorder. In addition, this term includes palliative treatment, that is, treatment designed for the relief of symptoms rather than the curing of the disease, pathological condition, or disorder; preventative treatment, that is, treatment directed to minimizing or partially or completely inhibiting the development of the associated disease, pathological condition, or disorder; and supportive treatment, that is, treatment employed to supplement another specific therapy directed toward the improvement of the associated disease, pathological condition, or disorder. In various aspects, the term covers any treatment of a subject, including a mammal (e.g., a human), and includes: (i) preventing the disease from occurring in a subject that can be predisposed to the disease but has not yet been diagnosed as having it; (ii) inhibiting the disease, i.e., arresting its development; or (iii) relieving the disease, i.e., causing regression of the disease. In one aspect, the subject is a mammal such as a primate, and, in a further aspect, the subject is a human. The term “subject” also includes domesticated animals (e.g., cats, dogs, etc.), livestock (e.g., cattle, horses, pigs, sheep, goats, etc.), and laboratory animals (e.g., mouse, rabbit, rat, guinea pig, fruit fly, etc.). As used herein, the term “prevent” or “preventing” refers to precluding, averting, obviating, forestalling, stopping, or hindering something from happening, especially by advance action. It is understood that where reduce, inhibit or prevent are used herein, unless specifically indicated otherwise, the use of the other two words is also expressly disclosed. As used herein, the term “diagnosed” means having been subjected to a physical examination by a person of skill, for example, a physician, and found to have a condition that can be diagnosed or treated by the compounds, compositions, or methods disclosed herein. As used herein, the terms “administering” and “administration” refer to any method of providing a pharmaceutical preparation to a subject. Such methods are well known to those skilled in the art and include, but are not limited to, oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, intravaginal administration, ophthalmic administration, intraaural administration, intracerebral administration, rectal administration, sublingual administration, buccal administration, and parenteral administration, including injectable such as intravenous administration, intra-arterial administration, intramuscular administration, and subcutaneous administration. Administration can be continuous or intermittent. In various aspects, a preparation can be administered therapeutically; that is, administered to treat an existing disease or condition. In further various aspects, a preparation can be administered prophylactically; that is, administered for prevention of a disease or condition. As used herein, the terms “effective amount” and “amount effective” refer to an amount that is sufficient to achieve the desired result or to have an effect on an undesired condition. For example, a “therapeutically effective amount” refers to an amount that is sufficient to achieve the desired therapeutic result or to have an effect on undesired symptoms, but is generally insufficient to cause adverse side effects. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration; the route of administration; the rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed and like factors well known in the medical arts. For example, it is well within the skill of the art to start doses of a compound at levels lower than those required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. If desired, the effective daily dose can be divided into multiple doses for purposes of administration. Consequently, single dose compositions can contain such amounts or submultiples thereof to make up the daily dose. The dosage can be adjusted by the individual physician in the event of any contraindications. Dosage can vary, and can be administered in one or more dose administrations daily, for one or several days. Guidance can be found in the literature for appropriate dosages for given classes of pharmaceutical products. In further various aspects, a preparation can be administered in a “prophylactically effective amount”; that is, an amount effective for prevention of a disease or condition. As used herein, “dosage form” means a pharmacologically active material in a medium, carrier, vehicle, or device suitable for administration to a subject. A dosage form can comprise a disclosed compound, a product of a disclosed method of making, or a salt, solvate, or polymorph thereof, in combination with a pharmaceutically acceptable excipient, such as a preservative, buffer, saline, or phosphate buffered saline. Dosage forms can be made using conventional pharmaceutical manufacturing and compounding techniques. Dosage forms can comprise inorganic or organic buffers (e.g., sodium or potassium salts of phosphate, carbonate, acetate, or citrate) and pH adjustment agents (e.g., hydrochloric acid, sodium or potassium hydroxide, salts of citrate or acetate, amino acids and their salts) antioxidants (e.g., ascorbic acid, alpha-tocopherol), surfactants (e.g., polysorbate 20, polysorbate 80, polyoxyethylene9-10 nonyl phenol, sodium desoxycholate), solution and/or cryo/lyo stabilizers (e.g., sucrose, lactose, mannitol, trehalose), osmotic adjustment agents (e.g., salts or sugars), antibacterial agents (e.g., benzoic acid, phenol, gentamicin), antifoaming agents (e.g., polydimethylsilozone), preservatives (e.g., thimerosal, 2- phenoxyethanol, EDTA), polymeric stabilizers and viscosity-adjustment agents (e.g., polyvinylpyrrolidone, poloxamer 488, carboxymethylcellulose) and co-solvents (e.g., glycerol, polyethylene glycol, ethanol). A dosage form formulated for injectable use can have a disclosed compound, a product of a disclosed method of making, or a salt, solvate, or polymorph thereof, suspended in sterile saline solution for injection together with a preservative. As used herein, “kit” means a collection of at least two components constituting the kit. Together, the components constitute a functional unit for a given purpose. Individual member components may be physically packaged together or separately. For example, a kit comprising an instruction for using the kit may or may not physically include the instruction with other individual member components. Instead, the instruction can be supplied as a separate member component, either in a paper form or an electronic form which may be supplied on computer readable memory device or downloaded from an internet website, or as recorded presentation. As used herein, “instruction(s)” means documents describing relevant materials or methodologies pertaining to a kit. These materials may include any combination of the following: background information, list of components and their availability information (purchase information, etc.), brief or detailed protocols for using the kit, trouble-shooting, references, technical support, and any other related documents. Instructions can be supplied with the kit or as a separate member component, either as a paper form or an electronic form which may be supplied on computer readable memory device or downloaded from an internet website, or as recorded presentation. Instructions can comprise one or multiple documents, and are meant to include future updates. As used herein, the terms “therapeutic agent” include any synthetic or naturally occurring biologically active compound or composition of matter which, when administered to an organism (human or nonhuman animal), induces a desired pharmacologic, immunogenic, and/or physiologic effect by local and/or systemic action. The term therefore encompasses those compounds or chemicals traditionally regarded as drugs, vaccines, and biopharmaceuticals including molecules such as proteins, peptides, hormones, nucleic acids, gene constructs and the like. Examples of therapeutic agents are described in well-known literature references such as the Merck Index (14^th edition), the Physicians' Desk Reference (64^th edition), and The Pharmacological Basis of Therapeutics (12^th edition) , and they include, without limitation, medicaments; vitamins; mineral supplements; substances used for the treatment, prevention, diagnosis, cure or mitigation of a disease or illness; substances that affect the structure or function of the body, or pro-drugs, which become biologically active or more active after they have been placed in a physiological environment. For example, the term “therapeutic agent” includes compounds or compositions for use in all of the major therapeutic areas including, but not limited to, adjuvants; anti-infectives such as antibiotics and antiviral agents; analgesics and analgesic combinations, anorexics, anti-inflammatory agents, anti-epileptics, local and general anesthetics, hypnotics, sedatives, antipsychotic agents, neuroleptic agents, antidepressants, anxiolytics, antagonists, neuron blocking agents, anticholinergic and cholinomimetic agents, antimuscarinic and muscarinic agents, antiadrenergics, antiarrhythmics, antihypertensive agents, hormones, and nutrients, antiarthritics, antiasthmatic agents, anticonvulsants, antihistamines, antinauseants, antineoplastics, antipruritics, antipyretics; antispasmodics, cardiovascular preparations (including calcium channel blockers, beta-blockers, beta-agonists and antiarrythmics), antihypertensives, diuretics, vasodilators; central nervous system stimulants; cough and cold preparations; decongestants; diagnostics; hormones; bone growth stimulants and bone resorption inhibitors; immunosuppressives; muscle relaxants; psychostimulants; sedatives; tranquilizers; proteins, peptides, and fragments thereof (whether naturally occurring, chemically synthesized or recombinantly produced); and nucleic acid molecules (polymeric forms of two or more nucleotides, either ribonucleotides (RNA) or deoxyribonucleotides (DNA) including both double- and single-stranded molecules, gene constructs, expression vectors, antisense molecules and the like), small molecules (e.g., doxorubicin) and other biologically active macromolecules such as, for example, proteins and enzymes. The agent may be a biologically active agent used in medical, including veterinary, applications and in agriculture, such as with plants, as well as other areas. The term "therapeutic agent" also includes without limitation, medicaments; vitamins; mineral supplements; substances used for the treatment, prevention, diagnosis, cure or mitigation of disease or illness; or substances which affect the structure or function of the body; or pro- drugs, which become biologically active or more active after they have been placed in a predetermined physiological environment. The term “pharmaceutically acceptable” describes a material that is not biologically or otherwise undesirable, i.e., without causing an unacceptable level of undesirable biological effects or interacting in a deleterious manner. As used herein, the term “derivative” refers to a compound having a structure derived from the structure of a parent compound (e.g., a compound disclosed herein) and whose structure is sufficiently similar to those disclosed herein and based upon that similarity, would be expected by one skilled in the art to exhibit the same or similar activities and utilities as the claimed compounds, or to induce, as a precursor, the same or similar activities and utilities as the claimed compounds. Exemplary derivatives include salts, esters, amides, salts of esters or amides, and N-oxides of a parent compound. As used herein, the term “pharmaceutically acceptable carrier” refers to sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like), carboxymethylcellulose and suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants. These compositions can also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents such as paraben, chlorobutanol, phenol, sorbic acid and the like. It can also be desirable to include isotonic agents such as sugars, sodium chloride and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by the inclusion of agents, such as aluminum monostearate and gelatin, which delay absorption. Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide, poly(orthoesters) and poly(anhydrides). Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissues. The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable media just prior to use. Suitable inert carriers can include sugars such as lactose. Desirably, at least 95% by weight of the particles of the active ingredient have an effective particle size in the range of 0.01 to 10 micrometers. A residue of a chemical species, as used in the specification and concluding claims, refers to the moiety that is the resulting product of the chemical species in a particular reaction scheme or subsequent formulation or chemical product, regardless of whether the moiety is actually obtained from the chemical species. Thus, an ethylene glycol residue in a polyester refers to one or more -OCH2CH2O- units in the polyester, regardless of whether ethylene glycol was used to prepare the polyester. Similarly, a sebacic acid residue in a polyester refers to one or more -CO(CH2)8CO- moieties in the polyester, regardless of whether the residue is obtained by reacting sebacic acid or an ester thereof to obtain the polyester. As used herein, the term “substituted” is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, and aromatic and nonaromatic substituents of organic compounds. Illustrative substituents include, for example, those described below. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this disclosure, the heteroatoms, such as nitrogen, can have hydrogen substituents and/or any permissible substituents of organic compounds described herein, which satisfy the valences of the heteroatoms. This disclosure is not intended to be limited in any manner by the permissible substituents of organic compounds. Also, the terms “substitution” or “substituted with” include the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, e.g., a compound that does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. It is also contemplated that, in certain aspects, unless expressly indicated to the contrary, individual substituents can be further optionally substituted (i.e., further substituted or unsubstituted). In defining various terms, “A¹,” “A²,” “A³,” and “A⁴” are used herein as generic symbols to represent various specific substituents. These symbols can be any substituent, not limited to those disclosed herein, and when they are defined to be certain substituents in one instance, they can, in another instance, be defined as some other substituents. The term “aliphatic” or “aliphatic group,” as used herein, denotes a hydrocarbon moiety that may be straight-chain (i.e., unbranched), branched, or cyclic (including fused, bridging, and spirofused polycyclic) and may be completely saturated or may contain one or more units of unsaturation, but which is not aromatic. Unless otherwise specified, aliphatic groups contain 1-20 carbon atoms. Aliphatic groups include, but are not limited to, linear or branched, alkyl, alkenyl, and alkynyl groups, and hybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl. The term “alkyl” as used herein is a branched or unbranched saturated hydrocarbon group of 1 to 24 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, isopentyl, s-pentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl, tetradecyl, hexadecyl, eicosyl, tetracosyl, and the like. The alkyl group can be branched or unbranched. The alkyl group can also be substituted or unsubstituted. For example, the alkyl group can be substituted with one or more groups including, but not limited to, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol, as described herein. A “lower alkyl” group is an alkyl group containing from one to six (e.g., from one to four) carbon atoms. The term alkyl group can also be a C1 alkyl, C1-C2 alkyl, C1-C3 alkyl, C1- C4 alkyl, C1-C5 alkyl, C1-C6 alkyl, C1-C7 alkyl, C1-C8 alkyl, C1-C9 alkyl, C1-C10 alkyl, and the like up to and including a C1-C24 alkyl. For example, the term “C1-C4 alkyl” includes methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, and t-butyl. Throughout the specification “alkyl” is generally used to refer to both unsubstituted alkyl groups and substituted alkyl groups; however, substituted alkyl groups are also specifically referred to herein by identifying the specific substituent(s) on the alkyl group. For example, the term “halogenated alkyl” or “haloalkyl” specifically refers to an alkyl group that is substituted with one or more halide, e.g., fluorine, chlorine, bromine, or iodine. Alternatively, the term “monohaloalkyl” specifically refers to an alkyl group that is substituted with a single halide, e.g. fluorine, chlorine, bromine, or iodine. The term “polyhaloalkyl” specifically refers to an alkyl group that is independently substituted with two or more halides, i.e. each halide substituent need not be the same halide as another halide substituent, nor do the multiple instances of a halide substituent need to be on the same carbon. The term “alkoxyalkyl” specifically refers to an alkyl group that is substituted with one or more alkoxy groups, as described below. The term “aminoalkyl” specifically refers to an alkyl group that is substituted with one or more amino groups. The term “hydroxyalkyl” specifically refers to an alkyl group that is substituted with one or more hydroxy groups. When “alkyl” is used in one instance and a specific term such as “hydroxyalkyl” is used in another, it is not meant to imply that the term “alkyl” does not also refer to specific terms such as “hydroxyalkyl” and the like. This practice is also used for other groups described herein. That is, while a term such as “cycloalkyl” refers to both unsubstituted and substituted cycloalkyl moieties, the substituted moieties can, in addition, be specifically identified herein; for example, a particular substituted cycloalkyl can be referred to as, e.g., an “alkylcycloalkyl.” Similarly, a substituted alkoxy can be specifically referred to as, e.g., a “halogenated alkoxy,” a particular substituted alkenyl can be, e.g., an “alkenylalcohol,” and the like. Again, the practice of using a general term, such as “cycloalkyl,” and a specific term, such as “alkylcycloalkyl,” is not meant to imply that the general term does not also include the specific term. The term “cycloalkyl” as used herein is a non-aromatic carbon-based ring composed of at least three carbon atoms. The term “cycloalkyl” includes monocyclic rings as well as ring systems including more than one cyclic ring, e.g. bicyclic rings. In ring systems including more than one cyclic ring, the rings of the “cycloalkyl” may be fused rings, bridged rings, or spirocyclic rings. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl, and the like. The term “heterocycloalkyl” is a type of cycloalkyl group as defined above, and is included within the meaning of the term “cycloalkyl,” where at least one of the carbon atoms of the ring is replaced with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. The cycloalkyl group and heterocycloalkyl group can be substituted or unsubstituted. For example, the cycloalkyl group and heterocycloalkyl group can be substituted with 0, 1, 2, 3, or 4 groups independently selected from C1-C4 alkyl, C3-C7 cycloalkyl, C1-C4 alkoxy, −NH2, (C1-C4) alkylamino, (C1-C4)(C1-C4) dialkylamino, ether, halogen, −OH, C1-C4 hydroxyalkyl, −NO2, silyl, sulfo-oxo, −SH, and C1-C4 thioalkyl, as described herein. The term “polyalkylene group” as used herein is a group having two or more CH₂ groups linked to one another. The polyalkylene group can be represented by the formula —(CH2)a— , where “a” is an integer of from 2 to 500. The terms “alkoxy” and “alkoxyl” as used herein to refer to an alkyl or cycloalkyl group bonded through an ether linkage; that is, an “alkoxy” group can be defined as —OA¹ where A¹ is alkyl or cycloalkyl as defined above. “Alkoxy” also includes polymers of alkoxy groups as just described; that is, an alkoxy can be a polyether such as —OA¹—OA² or — OA¹—(OA²)a—OA³, where “a” is an integer of from 1 to 200 and A¹, A², and A³ are alkyl and/or cycloalkyl groups. The term “alkenyl” as used herein is a hydrocarbon group of from 2 to 24 carbon atoms with a structural formula containing at least one carbon-carbon double bond. Asymmetric structures such as (A¹A²)C=C(A³A⁴) are intended to include both the E and Z isomers. This can be presumed in structural formulae herein wherein an asymmetric alkene is present, or it can be explicitly indicated by the bond symbol C=C. The alkenyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol, as described herein. The term “cycloalkenyl” as used herein is a non-aromatic carbon-based ring composed of at least three carbon atoms and containing at least one carbon-carbon double bound, i.e., C=C. Examples of cycloalkenyl groups include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, cyclohexadienyl, norbornenyl, and the like. The term “heterocycloalkenyl” is a type of cycloalkenyl group as defined above, and is included within the meaning of the term “cycloalkenyl,” where at least one of the carbon atoms of the ring is replaced with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. The cycloalkenyl group and heterocycloalkenyl group can be substituted or unsubstituted. For example, the cycloalkenyl group and heterocycloalkenyl group can be substituted with 0, 1, 2, 3, or 4 groups independently selected from C1-C4 alkyl, C3-C7 cycloalkyl, C1-C4 alkoxy, C2-C4 alkenyl, C3-C6 cycloalkenyl, C2-C4 alkynyl, aryl, heteroaryl, aldeyhyde, −NH2, (C1-C4) alkylamino, (C1- C4)(C1-C4) dialkylamino, carboxylic acid, ester, ether, halogen, −OH, C1-C4 hydroxyalkyl, ketone, azide, −NO₂, silyl, sulfo-oxo, −SH, and C1-C4 thioalkyl, as described herein. The term “alkynyl” as used herein is a hydrocarbon group of 2 to 24 carbon atoms with a structural formula containing at least one carbon-carbon triple bond. The alkynyl group can be unsubstituted or substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol, as described herein. The term “cycloalkynyl” as used herein is a non-aromatic carbon-based ring composed of at least seven carbon atoms and containing at least one carbon-carbon triple bound. Examples of cycloalkynyl groups include, but are not limited to, cycloheptynyl, cyclooctynyl, cyclononynyl, and the like. The term “heterocycloalkynyl” is a type of cycloalkenyl group as defined above, and is included within the meaning of the term “cycloalkynyl,” where at least one of the carbon atoms of the ring is replaced with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. The cycloalkynyl group and heterocycloalkynyl group can be substituted or unsubstituted. The cycloalkynyl group and heterocycloalkynyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, amino, carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol as described herein. The term “aromatic group” as used herein refers to a ring structure having cyclic clouds of delocalized π electrons above and below the plane of the molecule, where the π clouds contain (4n+2) π electrons. A further discussion of aromaticity is found in Morrison and Boyd, Organic Chemistry, (5th Ed., 1987), Chapter 13, entitled “Aromaticity,” pages 477- 497, incorporated herein by reference. The term “aromatic group” is inclusive of both aryl and heteroaryl groups. The term “aryl” as used herein is a group that contains any carbon-based aromatic group including, but not limited to, benzene, naphthalene, phenyl, biphenyl, anthracene, and the like. The aryl group can be substituted or unsubstituted. The aryl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, ─NH₂, carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol as described herein. The term “biaryl” is a specific type of aryl group and is included in the definition of “aryl.” In addition, the aryl group can be a single ring structure or comprise multiple ring structures that are either fused ring structures or attached via one or more bridging groups such as a carbon- carbon bond. For example, biaryl can be two aryl groups that are bound together via a fused ring structure, as in naphthalene, or are attached via one or more carbon-carbon bonds, as in biphenyl. Accordingly, the term “C6-C10 aryl” for example includes phenyl and naphthyl. The term “aldehyde” as used herein is represented by the formula —C(O)H. Throughout this specification “C(O)” or “CO” is a short hand notation for a carbonyl group, i.e., C=O. The terms “amine” or “amino” as used herein are represented by the formula —NA¹A², where A¹ and A² can be, independently, hydrogen or alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. A specific example of amino is ─NH₂. The term “alkylamino” as used herein is represented by the formula —NH(-alkyl) where alkyl is a described herein. Representative examples include, but are not limited to, methylamino group, ethylamino group, propylamino group, isopropylamino group, butylamino group, isobutylamino group, (sec-butyl)amino group, (tert-butyl)amino group, pentylamino group, isopentylamino group, (tert-pentyl)amino group, hexylamino group, and the like. The term “dialkylamino” as used herein is represented by the formula —N(-alkyl)2 where alkyl is a described herein. Representative examples include, but are not limited to, dimethylamino group, diethylamino group, dipropylamino group, diisopropylamino group, dibutylamino group, diisobutylamino group, di(sec-butyl)amino group, di(tert-butyl)amino group, dipentylamino group, diisopentylamino group, di(tert-pentyl)amino group, dihexylamino group, N-ethyl-N-methylamino group, N-methyl-N-propylamino group, N- ethyl-N-propylamino group and the like. The term “carboxylic acid” as used herein is represented by the formula —C(O)OH. The term “ester” as used herein is represented by the formula —OC(O)A¹ or —C(O)OA¹, where A¹ can be alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. The term “polyester” as used herein is represented by the formula —(A¹O(O)C-A²-C(O)O)a— or —(A¹O(O)C-A²-OC(O))a—, where A¹ and A² can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group described herein and “a” is an integer from 1 to 500. “Polyester” is as the term used to describe a group that is produced by the reaction between a compound having at least two carboxylic acid groups with a compound having at least two hydroxyl groups. The term “ether” as used herein is represented by the formula A¹OA², where A¹ and A² can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group described herein. The term “polyether” as used herein is represented by the formula —(A¹O-A²O)a—, where A¹ and A² can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group described herein and “a” is an integer of from 1 to 500. Examples of polyether groups include polyethylene oxide, polypropylene oxide, and polybutylene oxide. The terms “halo,” “halogen,” or “halide,” as used herein can be used interchangeably and refer to F, Cl, Br, or I. The terms “pseudohalide,” “pseudohalogen,” or “pseudohalo,” as used herein can be used interchangeably and refer to functional groups that behave substantially similar to halides. Such functional groups include, by way of example, cyano, thiocyanato, azido, trifluoromethyl, trifluoromethoxy, perfluoroalkyl, and perfluoroalkoxy groups. The term “heteroalkyl,” as used herein refers to an alkyl group containing at least one heteroatom. Suitable heteroatoms include, but are not limited to, O, N, Si, P and S, wherein the nitrogen, phosphorous and sulfur atoms are optionally oxidized, and the nitrogen heteroatom is optionally quaternized. Heteroalkyls can be substituted as defined above for alkyl groups. The term “heteroaryl,” as used herein refers to an aromatic group that has at least one heteroatom incorporated within the ring of the aromatic group. Examples of heteroatoms include, but are not limited to, nitrogen, oxygen, sulfur, and phosphorus, where N-oxides, sulfur oxides, and dioxides are permissible heteroatom substitutions. The heteroaryl group can be substituted or unsubstituted. The heteroaryl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol as described herein. Heteroaryl groups can be monocyclic, or alternatively fused ring systems. Heteroaryl groups include, but are not limited to, furyl, imidazolyl, pyrimidinyl, tetrazolyl, thienyl, pyridinyl, pyrrolyl, N-methylpyrrolyl, quinolinyl, isoquinolinyl, pyrazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridazinyl, pyrazinyl, benzofuranyl, benzodioxolyl, benzothiophenyl, indolyl, indazolyl, benzimidazolyl, imidazopyridinyl, pyrazolopyridinyl, and pyrazolopyrimidinyl. Further not limiting examples of heteroaryl groups include, but are not limited to, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiophenyl, pyrazolyl, imidazolyl, benzo[d]oxazolyl, benzo[d]thiazolyl, quinolinyl, quinazolinyl, indazolyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrazinyl, benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]oxadiazolyl, and pyrido[2,3-b]pyrazinyl. The terms “heterocycle” or “heterocyclyl,” as used herein can be used interchangeably and refer to single and multi-cyclic aromatic or non-aromatic ring systems in which at least one of the ring members is other than carbon. Thus, the term is inclusive of, but not limited to, “heterocycloalkyl”, “heteroaryl”, “bicyclic heterocycle” and “polycyclic heterocycle.” Heterocycle includes pyridine, pyrimidine, furan, thiophene, pyrrole, isoxazole, isothiazole, pyrazole, oxazole, thiazole, imidazole, oxazole, including, 1,2,3-oxadiazole, 1,2,5-oxadiazole and 1,3,4-oxadiazole, thiadiazole, including, 1,2,3-thiadiazole, 1,2,5-thiadiazole, and 1,3,4- thiadiazole, triazole, including, 1,2,3-triazole, 1,3,4-triazole, tetrazole, including 1,2,3,4- tetrazole and 1,2,4,5-tetrazole, pyridazine, pyrazine, triazine, including 1,2,4-triazine and 1,3,5-triazine, tetrazine, including 1,2,4,5-tetrazine, pyrrolidine, piperidine, piperazine, morpholine, azetidine, tetrahydropyran, tetrahydrofuran, dioxane, and the like. The term heterocyclyl group can also be a C2 heterocyclyl, C2-C3 heterocyclyl, C2-C4 heterocyclyl, C2-C5 heterocyclyl, C2-C6 heterocyclyl, C2-C7 heterocyclyl, C2-C8 heterocyclyl, C2-C9 heterocyclyl, C2-C10 heterocyclyl, C2-C11 heterocyclyl, and the like up to and including a C2-C18 heterocyclyl. For example, a C2 heterocyclyl comprises a group which has two carbon atoms and at least one heteroatom, including, but not limited to, aziridinyl, diazetidinyl, dihydrodiazetyl, oxiranyl, thiiranyl, and the like. Alternatively, for example, a C5 heterocyclyl comprises a group which has five carbon atoms and at least one heteroatom, including, but not limited to, piperidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, diazepanyl, pyridinyl, and the like. It is understood that a heterocyclyl group may be bound either through a heteroatom in the ring, where chemically possible, or one of carbons comprising the heterocyclyl ring. The term “bicyclic heterocycle” or “bicyclic heterocyclyl,” as used herein refers to a ring system in which at least one of the ring members is other than carbon. Bicyclic heterocyclyl encompasses ring systems wherein an aromatic ring is fused with another aromatic ring, or wherein an aromatic ring is fused with a non-aromatic ring. Bicyclic heterocyclyl encompasses ring systems wherein a benzene ring is fused to a 5- or a 6-membered ring containing 1, 2 or 3 ring heteroatoms or wherein a pyridine ring is fused to a 5- or a 6- membered ring containing 1, 2 or 3 ring heteroatoms. Bicyclic heterocyclic groups include, but are not limited to, indolyl, indazolyl, pyrazolo[1,5-a]pyridinyl, benzofuranyl, quinolinyl, quinoxalinyl, 1,3-benzodioxolyl, 2,3-dihydro-1,4-benzodioxinyl, 3,4-dihydro-2H-chromenyl, 1H-pyrazolo[4,3-c]pyridin-3-yl; 1H-pyrrolo[3,2-b]pyridin-3-yl; and 1H-pyrazolo[3,2- b]pyridin-3-yl. The term “heterocycloalkyl” as used herein refers to an aliphatic, partially unsaturated or fully saturated, 3- to 14-membered ring system, including single rings of 3 to 8 atoms and bi- and tricyclic ring systems. The heterocycloalkyl ring-systems include one to four heteroatoms independently selected from oxygen, nitrogen, and sulfur, wherein a nitrogen and sulfur heteroatom optionally can be oxidized and a nitrogen heteroatom optionally can be substituted. Representative heterocycloalkyl groups include, but are not limited to, pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, and tetrahydrofuryl. The term “hydroxy” or “hydroxyl” as used herein is represented by the formula —OH. The term “ketone” as used herein is represented by the formula A¹C(O)A², where A¹ and A² can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. The term “azide” or “azido” as used herein is represented by the formula —N3. The term “nitro” as used herein is represented by the formula —NO₂. The term “nitrile” or “cyano” as used herein is represented by the formula —CN or — C≡N. The term “silyl” as used herein is represented by the formula —SiA¹A²A³, where A¹, A², and A³ can be, independently, hydrogen or an alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. The term “sulfo-oxo” as used herein is represented by the formulas —S(O)A¹, — S(O)₂A¹, —OS(O)₂A¹, or —OS(O)₂OA¹, where A¹ can be hydrogen or an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. Throughout this specification “S(O)” is a short hand notation for S=O. The term “sulfonyl” is used herein to refer to the sulfo-oxo group represented by the formula —S(O)2A¹, where A¹ can be hydrogen or an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. The term “sulfone” as used herein is represented by the formula A¹S(O)₂A², where A¹ and A² can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. The term “sulfoxide” as used herein is represented by the formula A¹S(O)A², where A¹ and A² can be, independently, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, or heteroaryl group as described herein. The term “thiol” as used herein is represented by the formula —SH. “R¹,” “R²,” “R³,” “Rⁿ,” where n is an integer, as used herein can, independently, possess one or more of the groups listed above. For example, if R¹ is a straight chain alkyl group, one of the hydrogen atoms of the alkyl group can optionally be substituted with a hydroxyl group, an alkoxy group, an alkyl group, a halide, and the like. Depending upon the groups that are selected, a first group can be incorporated within second group or, alternatively, the first group can be pendant (i.e., attached) to the second group. For example, with the phrase “an alkyl group comprising an amino group,” the amino group can be incorporated within the backbone of the alkyl group. Alternatively, the amino group can be attached to the backbone of the alkyl group. The nature of the group(s) that is (are) selected will determine if the first group is embedded or attached to the second group. As described herein, compounds of the invention may contain “optionally substituted” moieties. In general, the term “substituted,” whether preceded by the term “optionally” or not, means that one or more hydrogen of the designated moiety are replaced with a suitable substituent. Unless otherwise indicated, an “optionally substituted” group may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position. Combinations of substituents envisioned by this invention are those that result in the formation of stable or chemically feasible compounds. In is also contemplated that, in certain aspects, unless expressly indicated to the contrary, individual substituents can be further optionally substituted (i.e., further substituted or unsubstituted). The term “stable,” as used herein, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and, in certain aspects, their recovery, purification, and use for one or more of the purposes disclosed herein. Suitable monovalent substituents on a substitutable carbon atom of an “optionally substituted” group are independently halogen; –(CH2)0–4R°; –(CH2)0–4OR°; -O(CH2)0-4R°, – O–(CH₂)_0–4C(O)OR°; –(CH₂)_0–4CH(OR°)₂; –(CH₂)_0–4SR°; –(CH₂)_0–4Ph, which may be substituted with R°; –(CH₂)_0–4O(CH₂)_0–1Ph which may be substituted with R°; –CH=CHPh, which may be substituted with R°; –(CH2)0–4O(CH2)0–1-pyridyl which may be substituted with R°; –NO2; –CN; –N3; -(CH2)0–4N(R°)2; –(CH2)0–4N(R°)C(O)R°; –N(R°)C(S)R°; – (CH2)0–4N(R°)C(O)NR°2; -N(R°)C(S)NR°2; –(CH2)0–4N(R°)C(O)OR°; – N(R°)N(R°)C(O)R°; -N(R°)N(R°)C(O)NR°2; -N(R°)N(R°)C(O)OR°; –(CH2)0–4C(O)R°; – C(S)R°; –(CH₂)_0–4C(O)OR°; –(CH₂)_0–4C(O)SR°; -(CH₂)_0–4C(O)OSiR°₃; –(CH₂)_0–4OC(O)R°; –OC(O)(CH₂)_0–4SR–, SC(S)SR°; –(CH₂)_0–4SC(O)R°; –(CH₂)_0–4C(O)NR°₂; –C(S)NR°₂; – C(S)SR°; -(CH2)0–4OC(O)NR°2; -C(O)N(OR°)R°; –C(O)C(O)R°; –C(O)CH2C(O)R°; – C(NOR°)R°; -(CH2)0–4SSR°; –(CH2)0–4S(O)2R°; –(CH2)0–4S(O)2OR°; –(CH2)0–4OS(O)2R°; – S(O)₂NR°₂; -(CH₂)_0–4S(O)R°; -N(R°)S(O)₂NR°₂; –N(R°)S(O)₂R°; –N(OR°)R°; – C(NH)NR°2; –P(O)2R°; -P(O)R°2; -OP(O)R°2; –OP(O)(OR°)2; SiR°3; –(C1–4 straight or branched alkylene)O–N(R°)₂; or –(C_1–4 straight or branched alkylene)C(O)O–N(R°)₂, wherein each R° may be substituted as defined below and is independently hydrogen, C_{1– 6} aliphatic, –CH₂Ph, –O(CH₂)_0–1Ph, -CH₂-(5-6 membered heteroaryl ring), or a 5–6– membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R°, taken together with their intervening atom(s), form a 3–12– membered saturated, partially unsaturated, or aryl mono– or bicyclic ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted as defined below. Suitable monovalent substituents on R° (or the ring formed by taking two independent occurrences of R° together with their intervening atoms), are independently halogen, – (CH₂)_0–2R^●, –(haloR^●), –(CH₂)_0–2OH, –(CH₂)_0–2OR^●, –(CH₂)_0–2CH(OR^●)₂; -O(haloR^●), –CN, –N3, –(CH2)0–2C(O)R^●, –(CH2)0–2C(O)OH, –(CH2)0–2C(O)OR^●, –(CH2)0–2SR^●, –(CH2)0–2SH, –(CH₂)_0–2NH₂, –(CH₂)_0–2NHR^●, –(CH₂)_0–2NR^● ₂, –NO₂, –SiR^● ₃, –OSiR^● ₃, -C(O)SR^● _, –(C_1–4 straight or branched alkylene)C(O)OR^●, or –SSR^● wherein each R^● is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently selected from C1–4 aliphatic, –CH2Ph, –O(CH2)0–1Ph, or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents on a saturated carbon atom of R° include =O and =S. Suitable divalent substituents on a saturated carbon atom of an “optionally substituted” group include the following: =O, =S, =NNR^* ₂, =NNHC(O)R^*, =NNHC(O)OR^*, =NNHS(O)2R^*, =NR^*, =NOR^*, –O(C(R^*2))2–3O–, or –S(C(R^*2))2–3S–, wherein each independent occurrence of R^* is selected from hydrogen, C_1–6 aliphatic which may be substituted as defined below, or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents that are bound to vicinal substitutable carbons of an “optionally substituted” group include: –O(CR^* ₂)_2–3O–, wherein each independent occurrence of R^* is selected from hydrogen, C1–6 aliphatic which may be substituted as defined below, or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable substituents on the aliphatic group of R^* include halogen, –R^●, -(haloR^●), -OH, – OR^●, –O(haloR^●), –CN, –C(O)OH, –C(O)OR^●, –NH₂, –NHR^●, –NR^● 2, or –NO₂, wherein each R^● is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C_1–4 aliphat –CH₂Ph, –O(CH₂)_0–1Ph, or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable substituents on a substitutable nitrogen of an “optionally substituted” group include –R^†, –NR^† ₂, –C(O)R^†, –C(O)OR^†, –C(O)C(O)R^†, –C(O)CH₂C(O)R^†, – S(O)2R^†, -S(O)2NR^†2, –C(S)NR^†2, –C(NH)NR^†2, or –N(R^†)S(O)2R^†; wherein each R^† is independently hydrogen, C_1–6 aliphatic which may be substituted as defined below, unsubstituted –OPh, or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R^†, taken together with their intervening atom(s) form an unsubstituted 3–12–membered saturated, partially unsaturated, or aryl mono– or bicyclic ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable substituents on the aliphatic group of R^† are independently halogen, – R^●, -(haloR^●), –OH, –OR^●, –O(haloR^●), –CN, –C(O)OH, –C(O)OR^●, –NH2, –NHR^●, –NR^●2, or –NO₂, wherein each R^● is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C1–4 aliphatic, –CH2Ph, –O(CH2)0–1Ph, or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. The term “leaving group” refers to an atom (or a group of atoms) with electron withdrawing ability that can be displaced as a stable species, taking with it the bonding electrons. Examples of suitable leaving groups include halides and sulfonate esters, including, but not limited to, triflate, mesylate, tosylate, and brosylate. The terms “hydrolysable group” and “hydrolysable moiety” refer to a functional group capable of undergoing hydrolysis, e.g., under basic or acidic conditions. Examples of hydrolysable residues include, without limitation, acid halides, activated carboxylic acids, and various protecting groups known in the art (see, for example, “Protective Groups in Organic Synthesis,” T. W. Greene, P. G. M. Wuts, Wiley-Interscience, 1999). The term “organic residue” defines a carbon containing residue, i.e., a residue comprising at least one carbon atom, and includes but is not limited to the carbon-containing groups, residues, or radicals defined hereinabove. Organic residues can contain various heteroatoms, or be bonded to another molecule through a heteroatom, including oxygen, nitrogen, sulfur, phosphorus, or the like. Examples of organic residues include but are not limited alkyl or substituted alkyls, alkoxy or substituted alkoxy, mono or di-substituted amino, amide groups, etc. Organic residues can preferably comprise 1 to 18 carbon atoms, 1 to 15, carbon atoms, 1 to 12 carbon atoms, 1 to 8 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms. In a further aspect, an organic residue can comprise 2 to 18 carbon atoms, 2 to 15, carbon atoms, 2 to 12 carbon atoms, 2 to 8 carbon atoms, 2 to 4 carbon atoms, or 2 to 4 carbon atoms. A very close synonym of the term “residue” is the term “radical,” which as used in the specification and concluding claims, refers to a fragment, group, or substructure of a molecule described herein, regardless of how the molecule is prepared. For example, a 2,4- thiazolidinedione radical in a particular compound has the structure: regardless of whether thiazolidinedione is used to prepare the compound. In some embodiments the radical (for example an alkyl) can be further modified (i.e., substituted alkyl) by having bonded thereto one or more “substituent radicals.” The number of atoms in a given radical is not critical to the present invention unless it is indicated to the contrary elsewhere herein. “Organic radicals,” as the term is defined and used herein, contain one or more carbon atoms. An organic radical can have, for example, 1-26 carbon atoms, 1-18 carbon atoms, 1- 12 carbon atoms, 1-8 carbon atoms, 1-6 carbon atoms, or 1-4 carbon atoms. In a further aspect, an organic radical can have 2-26 carbon atoms, 2-18 carbon atoms, 2-12 carbon atoms, 2-8 carbon atoms, 2-6 carbon atoms, or 2-4 carbon atoms. Organic radicals often have hydrogen bound to at least some of the carbon atoms of the organic radical. One example, of an organic radical that comprises no inorganic atoms is a 5, 6, 7, 8-tetrahydro-2-naphthyl radical. In some embodiments, an organic radical can contain 1-10 inorganic heteroatoms bound thereto or therein, including halogens, oxygen, sulfur, nitrogen, phosphorus, and the like. Examples of organic radicals include but are not limited to an alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, mono-substituted amino, di-substituted amino, acyloxy, cyano, carboxy, carboalkoxy, alkylcarboxamide, substituted alkylcarboxamide, dialkylcarboxamide, substituted dialkylcarboxamide, alkylsulfonyl, alkylsulfinyl, thioalkyl, thiohaloalkyl, alkoxy, substituted alkoxy, haloalkyl, haloalkoxy, aryl, substituted aryl, heteroaryl, heterocyclic, or substituted heterocyclic radicals, wherein the terms are defined elsewhere herein. A few non-limiting examples of organic radicals that include heteroatoms include alkoxy radicals, trifluoromethoxy radicals, acetoxy radicals, dimethylamino radicals and the like. “Inorganic radicals,” as the term is defined and used herein, contain no carbon atoms and therefore comprise only atoms other than carbon. Inorganic radicals comprise bonded combinations of atoms selected from hydrogen, nitrogen, oxygen, silicon, phosphorus, sulfur, selenium, and halogens such as fluorine, chlorine, bromine, and iodine, which can be present individually or bonded together in their chemically stable combinations. Inorganic radicals have 10 or fewer, or preferably one to six or one to four inorganic atoms as listed above bonded together. Examples of inorganic radicals include, but not limited to, amino, hydroxy, halogens, nitro, thiol, sulfate, phosphate, and like commonly known inorganic radicals. The inorganic radicals do not have bonded therein the metallic elements of the periodic table (such as the alkali metals, alkaline earth metals, transition metals, lanthanide metals, or actinide metals), although such metal ions can sometimes serve as a pharmaceutically acceptable cation for anionic inorganic radicals such as a sulfate, phosphate, or like anionic inorganic radical. Inorganic radicals do not comprise metalloids elements such as boron, aluminum, gallium, germanium, arsenic, tin, lead, or tellurium, or the noble gas elements, unless otherwise specifically indicated elsewhere herein. Compounds described herein can contain one or more double bonds and, thus, potentially give rise to cis/trans (E/Z) isomers, as well as other conformational isomers. Unless stated to the contrary, the invention includes all such possible isomers, as well as mixtures of such isomers. Unless stated to the contrary, a formula with chemical bonds shown only as solid lines and not as wedges or dashed lines contemplates each possible isomer, e.g., each enantiomer and diastereomer, and a mixture of isomers, such as a racemic or scalemic mixture. Compounds described herein can contain one or more asymmetric centers and, thus, potentially give rise to diastereomers and optical isomers. Unless stated to the contrary, the present invention includes all such possible diastereomers as well as their racemic mixtures, their substantially pure resolved enantiomers, all possible geometric isomers, and pharmaceutically acceptable salts thereof. Mixtures of stereoisomers, as well as isolated specific stereoisomers, are also included. During the course of the synthetic procedures used to prepare such compounds, or in using racemization or epimerization procedures known to those skilled in the art, the products of such procedures can be a mixture of stereoisomers. Many organic compounds exist in optically active forms having the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes d and l or (+) and (-) are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are non- superimposable mirror images of one another. A specific stereoisomer can also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric mixture. A 50:50 mixture of enantiomers is referred to as a racemic mixture. Many of the compounds described herein can have one or more chiral centers and therefore can exist in different enantiomeric forms. If desired, a chiral carbon can be designated with an asterisk (*). When bonds to the chiral carbon are depicted as straight lines in the disclosed formulas, it is understood that both the (R) and (S) configurations of the chiral carbon, and hence both enantiomers and mixtures thereof, are embraced within the formula. As is used in the art, when it is desired to specify the absolute configuration about a chiral carbon, one of the bonds to the chiral carbon can be depicted as a wedge (bonds to atoms above the plane) and the other can be depicted as a series or wedge of short parallel lines is (bonds to atoms below the plane). The Cahn-Ingold-Prelog system can be used to assign the (R) or (S) configuration to a chiral carbon. Compounds described herein comprise atoms in both their natural isotopic abundance and in non-natural abundance. The disclosed compounds can be isotopically-labeled or isotopically-substituted compounds identical to those described, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number typically found in nature. Examples of isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine and chlorine, such as ² H, ³ H, ¹³ C, ¹⁴ C, ¹⁵ N, ¹⁸ O, ¹⁷ O, ³⁵ S, ¹⁸ F and ³⁶ Cl, respectively. Compounds further comprise prodrugs thereof, and pharmaceutically acceptable salts of said compounds or of said prodrugs which contain the aforementioned isotopes and/or other isotopes of other atoms are within the scope of this invention. Certain isotopically-labeled compounds of the present invention, for example those into which radioactive isotopes such as ³ H and ¹⁴ C are incorporated, are useful in drug and/or substrate tissue distribution assays. Tritiated, i.e., ³ H, and carbon-14, i.e., ¹⁴ C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium, i.e., ² H, can afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances. Isotopically labeled compounds of the present invention and prodrugs thereof can generally be prepared by carrying out the procedures below, by substituting a readily available isotopically labeled reagent for a non- isotopically labeled reagent. The compounds described in the invention can be present as a solvate. In some cases, the solvent used to prepare the solvate is an aqueous solution, and the solvate is then often referred to as a hydrate. The compounds can be present as a hydrate, which can be obtained, for example, by crystallization from a solvent or from aqueous solution. In this connection, one, two, three or any arbitrary number of solvent or water molecules can combine with the compounds according to the invention to form solvates and hydrates. Unless stated to the contrary, the invention includes all such possible solvates. The term “co-crystal” means a physical association of two or more molecules which owe their stability through non-covalent interaction. One or more components of this molecular complex provide a stable framework in the crystalline lattice. In certain instances, the guest molecules are incorporated in the crystalline lattice as anhydrates or solvates, see e.g. “Crystal Engineering of the Composition of Pharmaceutical Phases. Do Pharmaceutical Co- crystals Represent a New Path to Improved Medicines?” Almarasson, O., et. al., The Royal Society of Chemistry, 1889-1896, 2004. Examples of co-crystals include p-toluenesulfonic acid and benzenesulfonic acid. It is also appreciated that certain compounds described herein can be present as an equilibrium of tautomers. For example, ketones with an α-hydrogen can exist in an equilibrium of the keto form and the enol form. Likewise, amides with an N-hydrogen can exist in an equilibrium of the amide form and the imidic acid form. As another example, pyrazoles can exist in two tautomeric forms, N¹- unsubstituted, 3-A³ and N¹-unsubstituted, 5-A³ as shown below. Unless stated to the contrary, the invention includes all such possible tautomers. It is known that chemical substances form solids which are present in different states of order which are termed polymorphic forms or modifications. The different modifications of a polymorphic substance can differ greatly in their physical properties. The compounds according to the invention can be present in different polymorphic forms, with it being possible for particular modifications to be metastable. Unless stated to the contrary, the invention includes all such possible polymorphic forms. In some aspects, a structure of a compound can be represented by a formula: , which is understood to be equivalent to a formula: wherein n is typically an integer. That is, Rⁿ is understood to represent five independent substituents, R^n(a), R^n(b), R^n(c), R^n(d), R^n(e). By “independent substituents,” it is meant that each R substituent can be independently defined. For example, if in one instance R^n(a) is halogen, then R^n(b) is not necessarily halogen in that instance. Certain materials, compounds, compositions, and components disclosed herein can be obtained commercially or readily synthesized using techniques generally known to those of skill in the art. For example, the starting materials and reagents used in preparing the disclosed compounds and compositions are either available from commercial suppliers such as Aldrich Chemical Co., (Milwaukee, Wis.), Acros Organics (Morris Plains, N.J.), Fisher Scientific (Pittsburgh, Pa.), or Sigma (St. Louis, Mo.) or are prepared by methods known to those skilled in the art following procedures set forth in references such as Fieser and Fieser’s Reagents for Organic Synthesis, Volumes 1-17 (John Wiley and Sons, 1991); Rodd’s Chemistry of Carbon Compounds, Volumes 1-5 and supplemental volumes (Elsevier Science Publishers, 1989); Organic Reactions, Volumes 1-40 (John Wiley and Sons, 1991); March’s Advanced Organic Chemistry, (John Wiley and Sons, 4th Edition); and Larock’s Comprehensive Organic Transformations (VCH Publishers Inc., 1989). Unless otherwise expressly stated, it is in no way intended that any method set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not actually recite an order to be followed by its steps or it is not otherwise specifically stated in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including: matters of logic with respect to arrangement of steps or operational flow; plain meaning derived from grammatical organization or punctuation; and the number or type of embodiments described in the specification. Disclosed are the components to be used to prepare the compositions of the invention as well as the compositions themselves to be used within the methods disclosed herein. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds cannot be explicitly disclosed, each is specifically contemplated and described herein. For example, if a particular compound is disclosed and discussed and a number of modifications that can be made to a number of molecules including the compounds are discussed, specifically contemplated is each and every combination and permutation of the compound and the modifications that are possible unless specifically indicated to the contrary. Thus, if a class of molecules A, B, and C are disclosed as well as a class of molecules D, E, and F and an example of a combination molecule, A-D is disclosed, then even if each is not individually recited each is individually and collectively contemplated meaning combinations, A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are considered disclosed. Likewise, any subset or combination of these is also disclosed. Thus, for example, the sub-group of A-E, B-F, and C- E would be considered disclosed. This concept applies to all aspects of this application including, but not limited to, steps in methods of making and using the compositions of the invention. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific embodiment or combination of embodiments of the methods of the invention. It is understood that the compositions disclosed herein have certain functions. Disclosed herein are certain structural requirements for performing the disclosed functions, and it is understood that there are a variety of structures that can perform the same function that are related to the disclosed structures, and that these structures will typically achieve the same result. B. COMPOUNDS Generally, the invention relates to compounds having a structure represented by a formula: , wherein m is selected from 0 and 1; wherein A is selected from ‒SO2‒ and ‒C(O)‒; and wherein Cy¹ is selected from a C3-C10 cycloalkyl, a C2-C9 heterocycloalkyl, a C6-C10 aryl, and a C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1- C4 alkyl), and Cy²; wherein R¹⁰ is selected from hydrogen and C1-C4 alkyl; and wherein Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒ CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, or a pharmaceutically acceptable salt thereof. In one aspect, the invention relates to compounds capable of inducing the degradation of proteins (e.g., KDM4B, VCL) relevant to the treatment of various cancers (e.g., a sarcoma, a carcinoma, a hematological cancer, a solid tumor, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, non-small cell lung carcinoma, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, melanoma, glioma, leukemia, lymphoma, chronic myeloproliferative disorder, myelodysplastic syndrome, myeloproliferative neoplasm, plasma cell neoplasm (myeloma)). Without wishing to be bound by theory, it is believed that the compounds of the invention, by way of inducing an altered specificity of an E3 ubiquitin ligase (e.g., cereblon) towards target cancer-associated proteins, such as KDM4 and VCL, are able to induce proteasome-mediated degradation of these proteins in a directed fashion via their recruitment to the E3 ubiquitin ligase and subsequent ubiquitination. Accordingly, the reduction of target cancer-associated protein levels is believed to be mainly attributable to a direct proteasome- mediated degradation of these proteins and not due to secondary changes in gene expression caused by changes in the level and/or activity of regulatory protein substrates of the E3 ubiquitin ligase. It is contemplated that each disclosed derivative can be optionally further substituted. It is also contemplated that any one or more derivative can be optionally omitted from the invention. It is understood that a disclosed compound can be provided by the disclosed methods. It is also understood that the disclosed compounds can be employed in the disclosed methods of using. 1. STRUCTURE In one aspect, disclosed are compounds having a structure represented by a formula: wherein m is selected from 0 and 1; wherein A is selected from ‒SO2‒ and ‒C(O)‒; and wherein Cy¹ is selected from a C3-C10 cycloalkyl, a C2-C9 heterocycloalkyl, a C6-C10 aryl, and a C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1- C4 alkyl), and Cy²; wherein R¹⁰ is selected from hydrogen and C1-C4 alkyl; and wherein Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒ CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, or a pharmaceutically acceptable salt thereof. In various aspects, the compound has a structure represented by a formula: , wherein Cy¹ is selected from a C3-C10 cycloalkyl, a C2-C9 heterocycloalkyl, a C6-C10 aryl, and a C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO2(C1-C4 alkyl), and Cy²; wherein R¹⁰ is selected from hydrogen and C1-C4 alkyl; and wherein Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, or a pharmaceutically acceptable salt thereof. In various aspects, the compound has a structure represented by a formula: wherein each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², provided that at least two of R^20a, R^20b, R^20c, R^20d, and R^20e is hydrogen, or wherein any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle, a 5-membered heterocycle, a 6- membered aryl, or a 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², wherein R¹⁰ is selected from hydrogen and C1-C4 alkyl; and wherein Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, or a pharmaceutically acceptable salt thereof. In various aspects, the compound has a structure represented by a formula: wherein each of R^20a, R^20b, R^20c, and R^20e is independently selected from hydrogen, halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², provided that at least two of R^20a, R^20b, R^20c, and R^20e is hydrogen, wherein R¹⁰ is selected from hydrogen and C1-C4 alkyl; and wherein Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, or a pharmaceutically acceptable salt thereof. In various aspects, the compound has a structure represented by a formula: wherein Z¹ is selected from ‒O‒, ‒S‒, and ‒N(R³⁰)‒; wherein R³⁰ is selected from hydrogen and C1-C4 alkyl; wherein each of R^21a, R^21b, and R^21c is independently selected from hydrogen, halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO2(C1-C4 alkyl), and Cy², or wherein any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl or a 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1- C4 alkyl), and Cy², wherein R¹⁰ is selected from hydrogen and C1-C4 alkyl; and wherein Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒ CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, or a pharmaceutically acceptable salt thereof. In various aspects, the compound has a structure represented by a formula: wherein Z¹ is selected from ‒O‒, ‒S‒, and ‒N(R³⁰)‒; wherein R³⁰ is selected from hydrogen and C1-C4 alkyl; wherein R^21a is selected from hydrogen, halogen, ‒CN, ‒NH2, ‒ OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒ NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², wherein R¹⁰ is selected from hydrogen and C1-C4 alkyl; and wherein Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒ OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, or a pharmaceutically acceptable salt thereof. In various aspects, the compound has a structure represented by a formula: , wherein Z² is selected from ‒O‒, ‒S‒, and ‒N(R³²)‒; wherein R³² is selected from hydrogen and C1-C4 alkyl; wherein Z³ is selected from ‒N= and ‒C(R³³)‒; wherein R³³ is selected from hydrogen and C1-C4 alkyl; wherein each of R^22a and R^22b is independently selected from hydrogen, halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1- C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy², or wherein R^22b is selected from hydrogen, halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², and wherein R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl or a 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy², wherein R¹⁰ is selected from hydrogen and C1-C4 alkyl; and wherein Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒ OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, or a pharmaceutically acceptable salt thereof. In various aspects, the compound has a structure represented by a formula: wherein Z² is selected from ‒O‒, ‒S‒, and ‒N(R³²)‒; wherein R³² is selected from hydrogen and C1-C4 alkyl; and wherein R^22b is selected from hydrogen, halogen, ‒CN, ‒ NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², wherein R¹⁰ is selected from hydrogen and C1-C4 alkyl; and wherein Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒ OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, or a pharmaceutically acceptable salt thereof. In various aspects, the compound is selected from: or a pharmaceutically acceptable salt thereof. In various aspects, the compound is selected from: or a pharmaceutically acceptable salt thereof. In various aspects, the compound is selected from: or a pharmaceutically acceptable salt thereof. In various aspects, m is selected from 0 and 1. In a further aspect, m is 0. In a still further aspect, m is 1. a. A GROUP In one aspect, A is selected from ‒SO₂‒ and ‒C(O)‒. In a further aspect, A is ‒SO₂‒. In a yet further aspect, A is ‒C(O)‒. b. Z¹ GROUPS In one aspect, Z¹ is selected from ‒O‒, ‒S‒, and ‒N(R³⁰)‒. In a further aspect, Z¹ is selected from ‒O‒ and ‒S‒. In a still further aspect, Z¹ is selected from ‒O‒ and ‒N(R³⁰)‒. In a yet further aspect, Z¹ is selected from ‒S‒ and ‒N(R³⁰)‒. In an even further aspect, Z¹ is ‒O‒. In an even still further aspect, Z¹ is ‒S‒. In an even yet further aspect, Z¹ is ‒N(R³⁰)‒. c. Z² GROUPS In one aspect, Z² is selected from ‒O‒, ‒S‒, and ‒N(R³²)‒. In a further aspect, Z² is selected from ‒O‒ and ‒N(R³²)‒. In a still further aspect, Z² is selected from ‒O‒ and ‒S‒. In a yet further aspect, Z² is selected from ‒S‒ and ‒N(R³²)‒. In various aspects, Z² is ‒O‒. In further aspect, Z² is ‒S‒. In a still further aspect, Z² is N(R³²)‒. d. Z³ GROUPS In one aspect, Z³ is selected from ‒N= and ‒C(R³³)‒. In a further aspect, Z³ is ‒N=. In a still further aspect, Z³ is ‒C(R³³)‒. e. R¹⁰ GROUPS In one aspect, R¹⁰ is selected from hydrogen and C1-C4 alkyl. In a further aspect, R¹⁰ is selected from hydrogen, methyl, ethyl, propyl, and isopropyl. In a further aspect, R¹⁰ is selected from hydrogen, methyl, and ethyl. In a still further aspect, R¹⁰ is selected from hydrogen and ethyl. In yet a further aspect, R¹⁰ is selected from hydrogen and methyl. In various aspects, R¹⁰ is C1-C4 alkyl. In a further aspect, R¹⁰ is selected from methyl, ethyl, propyl, and isopropyl. In a further aspect, R¹⁰ is selected from methyl and ethyl. In a still further aspect, R¹⁰ is ethyl. In yet a further aspect, R¹⁰ is methyl. In various aspects, R¹⁰ is hydrogen. f. R^20A, R^20B, R^20C, R^20D, AND R^20E GROUPS In one aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO2(C1-C4 alkyl), and Cy², provided that at least two of R^20a, R^20b, R^20c, R^20d, and R^20e is hydrogen, or wherein any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle, a 5- membered heterocycle, a 6-membered aryl, or a 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In various aspects, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO2(C1-C4 alkyl), and Cy², provided that at least two of R^20a, R^20b, R^20c, R^20d, and R^20e is hydrogen. In a further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒F, ‒Cl, ‒Br, ‒CN, ‒NH2, ‒OH, ‒NO2, methyl, ethyl, n-propyl, i- propyl, ethenyl, n-propenyl, i-propenyl, –CH2F, –CH2Cl, –CH2CH2F, –CH2CH2Cl, – CH2CH2CH2F, –CH2CH2CH2Cl, –CH(CH3)CH2F, –CH(CH3)CH2Cl, –CH2CN,–CH2CH2CN, –CH2CH2CH2CN, –CH(CH3)CH2CN, –CH2OH,–CH2CH2OH, –CH2CH2CH2OH, – CH(CH₃)CH₂OH, –OCH₂F, –OCHF₂, –OCF₃, –OCH₂Cl, –OCHCl₂, –OCCl₃, –OCH₂CH₂F, – OCH2CH2Cl, –OCH2CH2CH2F, –OCH2CH2CH2Cl, –OCH(CH3)CH2F, –OCH(CH3)CH2Cl, – OCH₃, –OCH₂CH₃, –OCH₂CH₂CH₃, –OCH(CH₃)CH₃, –NHCH₃, –NHCH₂CH₃, – NHCH2CH2CH3, –NHCH(CH3)CH3, –N(CH3)2, –N(CH2CH3)2, –N(CH2CH2CH3)2, – N(CH(CH₃)CH₃)₂, –N(CH₃)(CH₂CH₃), –N(CH₃)₂, –N(CH₂CH₃)₂, –N(CH₂CH₂CH₃)₂, – N(CH(CH3)CH3)2, and –N(CH3)(CH2CH3), –NHCH3, –NHCH2CH3, –NHCH2CH2CH3, – NHCH(CH₃)CH₃, ‒NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰C(O)Pr, ‒NR¹⁰CO₂Me, ‒NR¹⁰CO₂Et, ‒NR¹⁰CO2Pr, and Cy². In a still further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒F, ‒Cl, ‒CN, ‒NH₂, ‒OH, ‒NO₂, methyl, ethyl, ethenyl, –CH2F, –CH2Cl, –CH2CH2F, –CH2CH2Cl, –CH2CN,–CH2CH2CN, –CH2OH,– CH₂CH₂OH, –OCH₂F, –OCHF₂, –OCF₃, –OCH₂Cl, –OCHCl₂, –OCCl₃, –OCH₂CH₂F, – OCH2CH2Cl, –OCH3, –OCH2CH3, –NHCH3, –NHCH2CH3, –N(CH3)2, –N(CH2CH3)2, – N(CH₃)(CH₂CH₃), –N(CH₃)₂, –N(CH₂CH₃)₂, –NHCH₃, –NHCH₂CH₃, ‒NR¹⁰C(O)Me, ‒ NR¹⁰C(O)Et, ‒NR¹⁰CO2Me, ‒NR¹⁰CO2Et, and Cy². In a yet further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒F, ‒CN, ‒NH₂, ‒OH, ‒ NO2, methyl, –CH2F, –CH2Cl, –CH2CN, –CH2OH, –OCH2F, –OCHF2, –OCF3, –OCH2Cl, – OCHCl2, –OCCl3, –OCH3, –NHCH3, –N(CH3)2, –N(CH3)2, –NHCH3, ‒NR¹⁰C(O)Me, ‒ NR¹⁰CO₂Me, and Cy². In various aspects, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1- C4 alkyl), and Cy², provided that at least two of R^20a, R^20b, R^20c, R^20d, and R^20e is hydrogen. In a further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒F, ‒Cl, ‒Br, methyl, ethyl, n-propyl, i-propyl, ethenyl, n-propenyl, i-propenyl, ‒ NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰C(O)Pr, ‒NR¹⁰CO₂Me, ‒NR¹⁰CO₂Et, ‒NR¹⁰CO₂Pr, and Cy². In a still further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒F, ‒Cl, methyl, ethyl, ethenyl, ‒NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰CO₂Me, ‒NR¹⁰CO2Et, and Cy². In a yet further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒F, methyl, ‒NR¹⁰C(O)Me, ‒NR¹⁰CO₂Me, and Cy². In various aspects, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, halogen, C1-C4 haloalkyl, C1-C4 haloalkoxy, and Cy², provided that at least two of R^20a, R^20b, R^20c, R^20d, and R^20e is hydrogen. In a further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒F, ‒Cl, ‒Br, –CH2F, –CH2Cl, – CH2CH2F, –CH2CH2Cl, –CH2CH2CH2F, –CH2CH2CH2Cl, –CH(CH3)CH2F, – CH(CH3)CH2Cl, –OCH2F, –OCHF2, –OCF3, –OCH2Cl, –OCHCl2, –OCCl3, –OCH2CH2F, – OCH₂CH₂Cl, –OCH₂CH₂CH₂F, –OCH₂CH₂CH₂Cl, –OCH(CH₃)CH₂F, –OCH(CH₃)CH₂Cl, and Cy². In a still further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒F, ‒Cl, –CH₂F, –CH₂Cl, –CH₂CH₂F, –CH₂CH₂Cl, –OCH₂F, – OCHF2, –OCF3, –OCH2Cl, –OCHCl2, –OCCl3, –OCH2CH2F, –OCH2CH2Cl, and Cy². In a yet further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒F, –CH2F, –CH2Cl, –OCH2F, –OCHF2, –OCF3, –OCH2Cl, –OCHCl2, –OCCl3, and Cy². In various aspects, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒CN, C1-C4 cyanoalkyl, and Cy², provided that at least two of R^20a, R^20b, R^20c, R^20d, and R^20e is hydrogen. In a further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒CN, –CH₂CN,–CH₂CH₂CN, –CH₂CH₂CH₂CN, – CH(CH3)CH2CN, and Cy². In a still further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒CN, –CH₂CN,–CH₂CH₂CN, and Cy². In a yet further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒CN, –CH₂CN, and Cy². In various aspects, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒OH, C1-C4 hydroxyalkyl, C1-C4 alkoxy, and Cy², provided that at least two of R^20a, R^20b, R^20c, R^20d, and R^20e is hydrogen. In a further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒OH, –CH2OH,–CH2CH2OH, – CH₂CH₂CH₂OH, –CH(CH₃)CH₂OH, –OCH₃, –OCH₂CH₃, –OCH₂CH₂CH₃, –OCH(CH₃)CH₃, and Cy². In a still further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒OH, –CH₂OH,–CH₂CH₂OH, –OCH₃, –OCH₂CH₃, and Cy². In a yet further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒OH, –CH₂OH, –OCH₃, and Cy². In various aspects, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒NH₂, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², provided that at least two of R^20a, R^20b, R^20c, R^20d, and R^20e is hydrogen. In a further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒NH2, –NHCH3, –NHCH2CH3, – NHCH₂CH₂CH₃, –NHCH(CH₃)CH₃, –N(CH₃)₂, –N(CH₂CH₃)₂, –N(CH₂CH₂CH₃)₂, – N(CH(CH3)CH3)2, –N(CH3)(CH2CH3), –N(CH3)2, –N(CH2CH3)2, –N(CH2CH2CH3)2, – N(CH(CH3)CH3)2, and –N(CH3)(CH2CH3), –NHCH3, –NHCH2CH3, –NHCH2CH2CH3, – NHCH(CH3)CH3, ‒NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰C(O)Pr, ‒NR¹⁰CO2Me, ‒NR¹⁰CO2Et, ‒NR¹⁰CO2Pr, and Cy². In a still further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒NH₂, –NHCH₃, –NHCH₂CH₃, –N(CH₃)₂, – N(CH2CH3)2, –N(CH3)(CH2CH3), –N(CH3)2, –N(CH2CH3)2, –NHCH3, –NHCH2CH3, ‒ NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰CO₂Me, ‒NR¹⁰CO₂Et, and Cy². In a yet further aspect, each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, ‒NH2, – NHCH₃, –N(CH₃)₂, –N(CH₃)₂, –NHCH₃, ‒NR¹⁰C(O)Me, ‒NR¹⁰CO₂Me, and Cy². In various aspects, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle, a 5- membered heterocycle, a 6-membered aryl, or a 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle, a 5-membered heterocycle, a 6-membered aryl, or a 6-membered heteroaryl, and is substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO2(C1-C4 alkyl), and Cy². In a still further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5- membered cycle, a 5-membered heterocycle, a 6-membered aryl, or a 6-membered heteroaryl, and is substituted with 0 or 1 groups independently selected from halogen, ‒CN, ‒ NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a yet further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle, a 5- membered heterocycle, a 6-membered aryl, or a 6-membered heteroaryl, and is substituted with 1 group selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In an even further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle, a 5-membered heterocycle, a 6-membered aryl, or a 6- membered heteroaryl, and is unsubstituted. In various aspects, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a still further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle substituted with 0 or 1 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a yet further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle substituted with 1 group selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2- C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In an even further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle and is unsubstituted. In various aspects, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered heterocycle substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered heterocycle substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒ NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a still further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered heterocycle substituted with 0 or 1 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a yet further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered heterocycle substituted with 1 group selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1- C4 alkyl), and Cy². In an even further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered unsubstituted heterocycle. In various aspects, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a still further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl substituted with 0 or 1 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a yet further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl substituted with 1 group selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2- C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In an even further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 6-membered aryl. In various aspects, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 6-membered heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 6-membered heteroaryl substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒ NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a still further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 6-membered heteroaryl substituted with 0 or 1 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a yet further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 6-membered heteroaryl substituted with 1 group selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1- C4 alkyl), and Cy². In an even further aspect, any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 6-membered unsubstituted heteroaryl. g. R^21A, R^21B, AND R^21C GROUPS In one aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy², or wherein any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl or a 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒ CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In various aspects, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒F, ‒Cl, ‒Br, ‒CN, ‒NH2, ‒OH, ‒NO2, methyl, ethyl, n-propyl, i-propyl, ethenyl, n-propenyl, i-propenyl, –CH₂F, –CH₂Cl, –CH₂CH₂F, –CH₂CH₂Cl, –CH₂CH₂CH₂F, – CH2CH2CH2Cl, –CH(CH3)CH2F, –CH(CH3)CH2Cl, –CH2CN,–CH2CH2CN, – CH₂CH₂CH₂CN, –CH(CH₃)CH₂CN, –CH₂OH,–CH₂CH₂OH, –CH₂CH₂CH₂OH, – CH(CH3)CH2OH, –OCH2F, –OCHF2, –OCF3, –OCH2Cl, –OCHCl2, –OCCl3, –OCH2CH2F, – OCH₂CH₂Cl, –OCH₂CH₂CH₂F, –OCH₂CH₂CH₂Cl, –OCH(CH₃)CH₂F, –OCH(CH₃)CH₂Cl, – OCH3, –OCH2CH3, –OCH2CH2CH3, –OCH(CH3)CH3, –NHCH3, –NHCH2CH3, – NHCH₂CH₂CH₃, –NHCH(CH₃)CH₃, –N(CH₃)₂, –N(CH₂CH₃)₂, –N(CH₂CH₂CH₃)₂, – N(CH(CH3)CH3)2, –N(CH3)(CH2CH3), –N(CH3)2, –N(CH2CH3)2, –N(CH2CH2CH3)2, – N(CH(CH₃)CH₃)₂, and –N(CH₃)(CH₂CH₃), –NHCH₃, –NHCH₂CH₃, –NHCH₂CH₂CH₃, – NHCH(CH3)CH3, ‒NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰C(O)Pr, ‒NR¹⁰CO2Me, ‒NR¹⁰CO2Et, ‒NR¹⁰CO2Pr, and Cy². In a still further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒F, ‒Cl, ‒CN, ‒NH2, ‒OH, ‒NO2, methyl, ethyl, ethenyl, –CH2F, – CH2Cl, –CH2CH2F, –CH2CH2Cl, –CH2CN,–CH2CH2CN, –CH2OH,–CH2CH2OH, –OCH2F, – OCHF₂, –OCF₃, –OCH₂Cl, –OCHCl₂, –OCCl₃, –OCH₂CH₂F, –OCH₂CH₂Cl, –OCH₃, – OCH2CH3, –NHCH3, –NHCH2CH3, –N(CH3)2, –N(CH2CH3)2, –N(CH3)(CH2CH3), – N(CH₃)₂, –N(CH₂CH₃)₂, –NHCH₃, –NHCH₂CH₃, ‒NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒ NR¹⁰CO2Me, ‒NR¹⁰CO2Et, and Cy². In a yet further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒F, ‒CN, ‒NH₂, ‒OH, ‒NO₂, methyl, –CH₂F, – CH2Cl, –CH2CN, –CH2OH, –OCH2F, –OCHF2, –OCF3, –OCH2Cl, –OCHCl2, –OCCl3, – OCH₃, –NHCH₃, –N(CH₃)₂, –N(CH₃)₂, –NHCH₃, ‒NR¹⁰C(O)Me, ‒NR¹⁰CO₂Me, and Cy². In various aspects, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒F, ‒Cl, ‒Br, methyl, ethyl, n-propyl, i-propyl, ethenyl, n-propenyl, i-propenyl, , ‒ NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰C(O)Pr, ‒NR¹⁰CO2Me, ‒NR¹⁰CO2Et, ‒NR¹⁰CO2Pr, and Cy². In a still further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒F, ‒Cl, methyl, ethyl, ethenyl, ‒NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰CO2Me, ‒ NR¹⁰CO₂Et, and Cy². In a yet further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒F, methyl, ‒NR¹⁰C(O)Me, ‒NR¹⁰CO2Me, and Cy². In various aspects, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, halogen, C1-C4 haloalkyl, C1-C4 haloalkoxy. In a further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒F, ‒Cl, ‒Br, –CH2F, –CH2Cl, –CH2CH2F, – CH₂CH₂Cl, –CH₂CH₂CH₂F, –CH₂CH₂CH₂Cl, –CH(CH₃)CH₂F, –CH(CH₃)CH₂Cl, –OCH₂F, –OCHF2, –OCF3, –OCH2Cl, –OCHCl2, –OCCl3, –OCH2CH2F, –OCH2CH2Cl, – OCH₂CH₂CH₂F, –OCH₂CH₂CH₂Cl, –OCH(CH₃)CH₂F, –OCH(CH₃)CH₂Cl, and Cy². In a still further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒F, ‒ Cl, –CH₂F, –CH₂Cl, –CH₂CH₂F, –CH₂CH₂Cl, –OCH₂F, –OCHF₂, –OCF₃, –OCH₂Cl, – OCHCl2, –OCCl3, –OCH2CH2F, –OCH2CH2Cl, and Cy². In a yet further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒F, –CH₂F, –CH₂Cl, –OCH₂F, – OCHF2, –OCF3, –OCH2Cl, –OCHCl2, –OCCl3, and Cy². In various aspects, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒ CN, C1-C4 cyanoalkyl, and Cy². In a further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒CN, –CH₂CN,–CH₂CH₂CN, –CH₂CH₂CH₂CN, – CH(CH3)CH2CN, and Cy². In a still further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒CN, –CH2CN,–CH2CH2CN, and Cy². In a yet further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒CN, – CH2CN, and Cy². In various aspects, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒ OH, C1-C4 hydroxyalkyl, C1-C4 alkoxy, and Cy². In a further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒OH, –CH₂OH,–CH₂CH₂OH, – CH2CH2CH2OH, –CH(CH3)CH2OH, –OCH3, –OCH2CH3, –OCH2CH2CH3, –OCH(CH3)CH3, and Cy². In a still further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒OH, –CH2OH,–CH2CH2OH, –OCH3, –OCH2CH3, and Cy². In a yet further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒OH, –CH₂OH, –OCH3, and Cy². In various aspects, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒ NH2, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1- C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒NH2, –NHCH3, –NHCH2CH3, –NHCH2CH2CH3, –NHCH(CH₃)CH₃, –N(CH₃)₂, –N(CH₂CH₃)₂, –N(CH₂CH₂CH₃)₂, –N(CH(CH₃)CH₃)₂, – N(CH3)(CH2CH3), –N(CH3)2, –N(CH2CH3)2, –N(CH2CH2CH3)2, –N(CH(CH3)CH3)2, and – N(CH₃)(CH₂CH₃), –NHCH₃, –NHCH₂CH₃, –NHCH₂CH₂CH₃, –NHCH(CH₃)CH₃, ‒ NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰C(O)Pr, ‒NR¹⁰CO2Me, ‒NR¹⁰CO2Et, ‒NR¹⁰CO2Pr, and Cy². In a still further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒NH₂, –NHCH₃, –NHCH₂CH₃, –N(CH₃)₂, –N(CH₂CH₃)₂, –N(CH₃)(CH₂CH₃), – N(CH3)2, –N(CH2CH3)2, –NHCH3, –NHCH2CH3, ‒NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒ NR¹⁰CO₂Me, ‒NR¹⁰CO₂Et, and Cy². In a yet further aspect, each of R^21a, R^21b, and R^21c is independently selected from hydrogen, ‒NH2, –NHCH3, –N(CH3)2, –N(CH3)2, –NHCH3, ‒ NR¹⁰C(O)Me, ‒NR¹⁰CO₂Me, and Cy². In various aspects, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle, a 5-membered heterocycle, a 6-membered aryl, or a 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2- C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle, a 5-membered heterocycle, a 6-membered aryl, or a 6- membered heteroaryl, and is substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a still further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle, a 5- membered heterocycle, a 6-membered aryl, or a 6-membered heteroaryl, and is substituted with 0 or 1 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a yet further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle, a 5-membered heterocycle, a 6-membered aryl, or a 6-membered heteroaryl, and is substituted with 1 group selected from halogen, ‒ CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In an even further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle, a 5-membered heterocycle, a 6-membered aryl, or a 6-membered heteroaryl, and is unsubstituted. In various aspects, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2- C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a still further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle substituted with 0 or 1 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a yet further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle substituted with 1 group selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In an even further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 5- membered cycle. In various aspects, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 5-membered heterocycle substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 5-membered heterocycle substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a still further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 5- membered heterocycle substituted with 0 or 1 groups independently selected from halogen, ‒ CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a yet further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 5-membered heterocycle substituted with 1 group selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In an even further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 5-membered heterocycle. In various aspects, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a still further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl substituted with 0 or 1 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a yet further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl substituted with 1 group selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In an even further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 6- membered aryl. In various aspects, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 6-membered heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 6-membered heteroaryl substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a still further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 6- membered heteroaryl substituted with 0 or 1 groups independently selected from halogen, ‒ CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a yet further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 6-membered heteroaryl substituted with 1 group selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In an even further aspect, any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 6-membered heteroaryl. h. R^22A, R^22B, AND R³³ GROUPS In one aspect, each of R^22a and R^22b is independently selected from hydrogen, halogen, ‒ CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy², and R³³ is selected from hydrogen and C1-C4 alkyl; or R^22b is selected from halogen, ‒ CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy², and R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl or a 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In various aspects, each of R^22a and R^22b is independently selected from hydrogen, halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², and R³³ is selected from hydrogen and C1-C4 alkyl. In various aspects, each of R^22a and R^22b is independently selected from hydrogen, halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒F, ‒Cl, ‒Br, ‒CN, ‒NH₂, ‒OH, ‒NO₂, methyl, ethyl, n-propyl, i-propyl, ethenyl, n-propenyl, i-propenyl, –CH2F, –CH2Cl, –CH2CH2F, –CH2CH2Cl, –CH2CH2CH2F, – CH₂CH₂CH₂Cl, –CH(CH₃)CH₂F, –CH(CH₃)CH₂Cl, –CH₂CN,–CH₂CH₂CN, – CH2CH2CH2CN, –CH(CH3)CH2CN, –CH2OH,–CH2CH2OH, –CH2CH2CH2OH, – CH(CH₃)CH₂OH, –OCH₂F, –OCHF₂, –OCF₃, –OCH₂Cl, –OCHCl₂, –OCCl₃, –OCH₂CH₂F, – OCH2CH2Cl, –OCH2CH2CH2F, –OCH2CH2CH2Cl, –OCH(CH3)CH2F, –OCH(CH3)CH2Cl, – OCH₃, –OCH₂CH₃, –OCH₂CH₂CH₃, –OCH(CH₃)CH₃, –NHCH₃, –NHCH₂CH₃, – NHCH2CH2CH3, –NHCH(CH3)CH3, –N(CH3)2, –N(CH2CH3)2, –N(CH2CH2CH3)2, – N(CH(CH3)CH3)2, –N(CH3)(CH2CH3), –N(CH3)2, –N(CH2CH3)2, –N(CH2CH2CH3)2, – N(CH(CH₃)CH₃)₂, and –N(CH₃)(CH₂CH₃), –NHCH₃, –NHCH₂CH₃, –NHCH₂CH₂CH₃, – NHCH(CH3)CH3, ‒NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰C(O)Pr, ‒NR¹⁰CO2Me, ‒NR¹⁰CO2Et, ‒NR¹⁰CO₂Pr, and Cy². In a still further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒F, ‒Cl, ‒CN, ‒NH2, ‒OH, ‒NO2, methyl, ethyl, ethenyl, –CH2F, – CH₂Cl, –CH₂CH₂F, –CH₂CH₂Cl, –CH₂CN,–CH₂CH₂CN, –CH₂OH,–CH₂CH₂OH, –OCH₂F, – OCHF2, –OCF3, –OCH2Cl, –OCHCl2, –OCCl3, –OCH2CH2F, –OCH2CH2Cl, –OCH3, – OCH₂CH₃, –NHCH₃, –NHCH₂CH₃, –N(CH₃)₂, –N(CH₂CH₃)₂, –N(CH₃)(CH₂CH₃), – N(CH3)2, –N(CH2CH3)2, –NHCH3, –NHCH2CH3, ‒NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒ NR¹⁰CO₂Me, ‒NR¹⁰CO₂Et, and Cy². In a yet further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒F, ‒CN, ‒NH2, ‒OH, ‒NO2, methyl, –CH2F, – CH₂Cl, –CH₂CN, –CH₂OH, –OCH₂F, –OCHF₂, –OCF₃, –OCH₂Cl, –OCHCl₂, –OCCl₃, – OCH3, –NHCH3, –N(CH3)2, –N(CH3)2, –NHCH3, ‒NR¹⁰C(O)Me, ‒NR¹⁰CO2Me, and Cy². In various aspects, each of R^22a and R^22b is independently selected from hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒F, ‒Cl, ‒Br, methyl, ethyl, n-propyl, i-propyl, ethenyl, n-propenyl, i-propenyl, , ‒ NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰C(O)Pr, ‒NR¹⁰CO2Me, ‒NR¹⁰CO2Et, ‒NR¹⁰CO2Pr, and Cy². In a still further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒F, ‒Cl, methyl, ethyl, ethenyl, ‒NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰CO2Me, ‒NR¹⁰CO2Et, and Cy². In a yet further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒F, methyl, ‒NR¹⁰C(O)Me, ‒NR¹⁰CO2Me, and Cy². In various aspects, each of R^22a and R^22b is independently selected from hydrogen, halogen, C1-C4 haloalkyl, C1-C4 haloalkoxy. In a further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒F, ‒Cl, ‒Br, –CH₂F, –CH₂Cl, –CH₂CH₂F, – CH2CH2Cl, –CH2CH2CH2F, –CH2CH2CH2Cl, –CH(CH3)CH2F, –CH(CH3)CH2Cl, –OCH2F, –OCHF₂, –OCF₃, –OCH₂Cl, –OCHCl₂, –OCCl₃, –OCH₂CH₂F, –OCH₂CH₂Cl, – OCH2CH2CH2F, –OCH2CH2CH2Cl, –OCH(CH3)CH2F, –OCH(CH3)CH2Cl, and Cy². In a still further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒F, ‒Cl, – CH2F, –CH2Cl, –CH2CH2F, –CH2CH2Cl, –OCH2F, –OCHF2, –OCF3, –OCH2Cl, –OCHCl2, – OCCl₃, –OCH₂CH₂F, –OCH₂CH₂Cl, and Cy². In a yet further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒F, –CH2F, –CH2Cl, –OCH2F, –OCHF2, –OCF3, – OCH₂Cl, –OCHCl₂, –OCCl₃, and Cy². In various aspects, each of R^22a and R^22b is independently selected from hydrogen, ‒CN, C1-C4 cyanoalkyl, and Cy². In a further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒CN, –CH₂CN,–CH₂CH₂CN, –CH₂CH₂CH₂CN, –CH(CH₃)CH₂CN, and Cy². In a still further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒CN, –CH₂CN,–CH₂CH₂CN, and Cy². In a yet further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒CN, –CH2CN, and Cy². In various aspects, each of R^22a and R^22b is independently selected from hydrogen, ‒OH, C1-C4 hydroxyalkyl, C1-C4 alkoxy, and Cy². In a further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒OH, –CH₂OH,–CH₂CH₂OH, –CH₂CH₂CH₂OH, – CH(CH3)CH2OH, –OCH3, –OCH2CH3, –OCH2CH2CH3, –OCH(CH3)CH3, and Cy². In a still further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒OH, – CH2OH,–CH2CH2OH, –OCH3, –OCH2CH3, and Cy². In a yet further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒OH, –CH₂OH, –OCH₃, and Cy². In various aspects, each of R^22a and R^22b is independently selected from hydrogen, ‒NH2, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒NH2, –NHCH3, –NHCH2CH3, –NHCH2CH2CH3, – NHCH(CH3)CH3, –N(CH3)2, –N(CH2CH3)2, –N(CH2CH2CH3)2, –N(CH(CH3)CH3)2, – N(CH3)(CH2CH3), –N(CH3)2, –N(CH2CH3)2, –N(CH2CH2CH3)2, –N(CH(CH3)CH3)2, and – N(CH₃)(CH₂CH₃), –NHCH₃, –NHCH₂CH₃, –NHCH₂CH₂CH₃, –NHCH(CH₃)CH₃, ‒ NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰C(O)Pr, ‒NR¹⁰CO2Me, ‒NR¹⁰CO2Et, ‒NR¹⁰CO2Pr, and Cy². In a still further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒NH2, –NHCH3, –NHCH2CH3, –N(CH3)2, –N(CH2CH3)2, –N(CH3)(CH2CH3), –N(CH3)2, – N(CH₂CH₃)₂, –NHCH₃, –NHCH₂CH₃, ‒NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰CO₂Me, ‒ NR¹⁰CO2Et, and Cy². In a yet further aspect, each of R^22a and R^22b is independently selected from hydrogen, ‒NH₂, –NHCH₃, –N(CH₃)₂, –N(CH₃)₂, –NHCH₃, ‒NR¹⁰C(O)Me, ‒ NR¹⁰CO2Me, and Cy². In various aspects, R³³ is selected from hydrogen and C1-C4 alkyl. In a further aspect, R³² is selected from hydrogen, methyl, ethyl, propyl, and isopropyl. In a further aspect, R³³ is selected from hydrogen, methyl, and ethyl. In a still further aspect, R³³ is selected from hydrogen and ethyl. In yet a further aspect, R³³ is selected from hydrogen and methyl. In various aspects, R³³ is C1-C4 alkyl. In a further aspect, R³³ is selected from methyl, ethyl, propyl, and isopropyl. In a further aspect, R³³ is selected from methyl and ethyl. In a still further aspect, R³³ is ethyl. In yet a further aspect, R³³ is methyl. In various aspects, R³³ is hydrogen. In various aspects, R^22b is selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy², and R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl or a 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO₂(C1-C4 alkyl), and Cy². In various aspects, R^22b is selected from hydrogen, halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, R^22b is selected from hydrogen, ‒F, ‒Cl, ‒Br, ‒CN, ‒NH2, ‒OH, ‒NO2, methyl, ethyl, n- propyl, i-propyl, ethenyl, n-propenyl, i-propenyl, –CH2F, –CH2Cl, –CH2CH2F, –CH2CH2Cl, –CH2CH2CH2F, –CH2CH2CH2Cl, –CH(CH3)CH2F, –CH(CH3)CH2Cl, –CH2CN,– CH2CH2CN, –CH2CH2CH2CN, –CH(CH3)CH2CN, –CH2OH,–CH2CH2OH, – CH₂CH₂CH₂OH, –CH(CH₃)CH₂OH, –OCH₂F, –OCHF₂, –OCF₃, –OCH₂Cl, –OCHCl₂, – OCCl3, –OCH2CH2F, –OCH2CH2Cl, –OCH2CH2CH2F, –OCH2CH2CH2Cl, – OCH(CH₃)CH₂F, –OCH(CH₃)CH₂Cl, –OCH₃, –OCH₂CH₃, –OCH₂CH₂CH₃, – OCH(CH3)CH3, –NHCH3, –NHCH2CH3, –NHCH2CH2CH3, –NHCH(CH3)CH3, –N(CH3)2, – N(CH₂CH₃)₂, –N(CH₂CH₂CH₃)₂, –N(CH(CH₃)CH₃)₂, –N(CH₃)(CH₂CH₃), –N(CH₃)₂, – N(CH2CH3)2, –N(CH2CH2CH3)2, –N(CH(CH3)CH3)2, and –N(CH3)(CH2CH3), –NHCH3, – NHCH₂CH₃, –NHCH₂CH₂CH₃, –NHCH(CH₃)CH₃, ‒NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒ NR¹⁰C(O)Pr, ‒NR¹⁰CO2Me, ‒NR¹⁰CO2Et, ‒NR¹⁰CO2Pr, and Cy². In a still further aspect, R^22b is selected from hydrogen, ‒F, ‒Cl, ‒CN, ‒NH₂, ‒OH, ‒NO₂, methyl, ethyl, ethenyl, – CH2F, –CH2Cl, –CH2CH2F, –CH2CH2Cl, –CH2CN,–CH2CH2CN, –CH2OH,–CH2CH2OH, – OCH₂F, –OCHF₂, –OCF₃, –OCH₂Cl, –OCHCl₂, –OCCl₃, –OCH₂CH₂F, –OCH₂CH₂Cl, – OCH3, –OCH2CH3, –NHCH3, –NHCH2CH3, –N(CH3)2, –N(CH2CH3)2, –N(CH3)(CH2CH3), – N(CH₃)₂, –N(CH₂CH₃)₂, –NHCH₃, –NHCH₂CH₃, ‒NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒ NR¹⁰CO2Me, ‒NR¹⁰CO2Et, and Cy². In a yet further aspect, R^22b is selected from hydrogen, ‒F, ‒CN, ‒NH₂, ‒OH, ‒NO₂, methyl, –CH₂F, –CH₂Cl, –CH₂CN, –CH₂OH, –OCH₂F, – OCHF2, –OCF3, –OCH2Cl, –OCHCl2, –OCCl3, –OCH3, –NHCH3, –N(CH3)2, –N(CH3)2, – NHCH3, ‒NR¹⁰C(O)Me, ‒NR¹⁰CO2Me, and Cy². In various aspects, R^22b is selected from hydrogen, halogen, C1-C4 alkyl, C2-C4 alkenyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, R^22b is selected from hydrogen, ‒F, ‒Cl, ‒Br, methyl, ethyl, n-propyl, i-propyl, ethenyl, n-propenyl, i-propenyl, , ‒NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰C(O)Pr, ‒NR¹⁰CO₂Me, ‒NR¹⁰CO₂Et, ‒ NR¹⁰CO2Pr, and Cy². In a still further aspect, R^22b is selected from hydrogen, ‒F, ‒Cl, methyl, ethyl, ethenyl, ‒NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰CO₂Me, ‒NR¹⁰CO₂Et, and Cy². In a yet further aspect, R^22b is selected from hydrogen, ‒F, methyl, ‒NR¹⁰C(O)Me, ‒ NR¹⁰CO₂Me, and Cy². In various aspects, R^22b is selected from hydrogen, halogen, C1-C4 haloalkyl, C1-C4 haloalkoxy. In a further aspect, R^22b is selected from hydrogen, ‒F, ‒Cl, ‒Br, –CH₂F, – CH2Cl, –CH2CH2F, –CH2CH2Cl, –CH2CH2CH2F, –CH2CH2CH2Cl, –CH(CH3)CH2F, – CH(CH₃)CH₂Cl, –OCH₂F, –OCHF₂, –OCF₃, –OCH₂Cl, –OCHCl₂, –OCCl₃, –OCH₂CH₂F, – OCH2CH2Cl, –OCH2CH2CH2F, –OCH2CH2CH2Cl, –OCH(CH3)CH2F, –OCH(CH3)CH2Cl, and Cy². In a still further aspect, R^22b is selected from hydrogen, ‒F, ‒Cl, –CH2F, –CH2Cl, – CH2CH2F, –CH2CH2Cl, –OCH2F, –OCHF2, –OCF3, –OCH2Cl, –OCHCl2, –OCCl3, – OCH2CH2F, –OCH2CH2Cl, and Cy². In a yet further aspect, R^22b is selected from hydrogen, ‒F, –CH₂F, –CH₂Cl, –OCH₂F, –OCHF₂, –OCF₃, –OCH₂Cl, –OCHCl₂, –OCCl₃, and Cy². In various aspects, R^22b is selected selected from hydrogen, ‒CN, C1-C4 cyanoalkyl, and Cy². In a further aspect, R^22b is selected from hydrogen, ‒CN, –CH₂CN,–CH₂CH₂CN, – CH2CH2CH2CN, –CH(CH3)CH2CN, and Cy². In a still further aspect, R^22b is selected from hydrogen, ‒CN, –CH₂CN,–CH₂CH₂CN, and Cy². In a yet further aspect, R^22b is selected from hydrogen, ‒CN, –CH2CN, and Cy². In various aspects, R^22b is selected from hydrogen, ‒OH, C1-C4 hydroxyalkyl, C1-C4 alkoxy, and Cy². In a further aspect, R^22b is selected from hydrogen, ‒OH, –CH2OH,– CH₂CH₂OH, –CH₂CH₂CH₂OH, –CH(CH₃)CH₂OH, –OCH₃, –OCH₂CH₃, –OCH₂CH₂CH₃, – OCH(CH3)CH3, and Cy². In a still further aspect, R^22b is selected from hydrogen, ‒OH, – CH₂OH,–CH₂CH₂OH, –OCH₃, –OCH₂CH₃, and Cy². In a yet further aspect, R^22b is selected from hydrogen, ‒OH, –CH2OH, –OCH3, and Cy². In various aspects, R^22b is selected from hydrogen, ‒NH₂, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a further aspect, R^22b is selected selected from hydrogen, ‒NH₂, –NHCH₃, –NHCH2CH3, –NHCH2CH2CH3, –NHCH(CH3)CH3, –N(CH3)2, –N(CH2CH3)2, – N(CH2CH2CH3)2, –N(CH(CH3)CH3)2, –N(CH3)(CH2CH3), –N(CH3)2, –N(CH2CH3)2, – N(CH₂CH₂CH₃)₂, –N(CH(CH₃)CH₃)₂, and –N(CH₃)(CH₂CH₃), –NHCH₃, –NHCH₂CH₃, – NHCH2CH2CH3, –NHCH(CH3)CH3, ‒NR¹⁰C(O)Me, ‒NR¹⁰C(O)Et, ‒NR¹⁰C(O)Pr, ‒ NR¹⁰CO₂Me, ‒NR¹⁰CO₂Et, ‒NR¹⁰CO₂Pr, and Cy². In a still further aspect, R^22b is selected from hydrogen, ‒NH2, –NHCH3, –NHCH2CH3, –N(CH3)2, –N(CH2CH3)2, – N(CH₃)(CH₂CH₃), –N(CH₃)₂, –N(CH₂CH₃)₂, –NHCH₃, –NHCH₂CH₃, ‒NR¹⁰C(O)Me, ‒ NR¹⁰C(O)Et, ‒NR¹⁰CO2Me, ‒NR¹⁰CO2Et, and Cy². In a yet further aspect, R^22b is selected selected from hydrogen, ‒NH₂, –NHCH₃, –N(CH₃)₂, –N(CH₃)₂, –NHCH₃, ‒NR¹⁰C(O)Me, ‒ NR¹⁰CO2Me, and Cy². In various aspects, R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl or a 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a further aspect, R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6- membered aryl or a 6-membered heteroaryl, and is substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a still further aspect, R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl or a 6- membered heteroaryl, and is substituted with 0 or 1 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a yet further aspect, R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl or a 6-membered heteroaryl, and is substituted with 1 group selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2- C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In an even further aspect, R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6- membered aryl or a 6-membered heteroaryl, and is unsubstituted. In various aspects, R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a still further aspect, R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl substituted with 0 or 1 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒ NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a yet further aspect, R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl substituted with 1 group selected from halogen, ‒CN, ‒NH2, ‒ OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In an even further aspect, R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 6-membered aryl. In various aspects, R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6-membered heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6-membered heteroaryl substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a still further aspect, R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6-membered heteroaryl substituted with 0 or 1 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1- C4 alkyl), and Cy². In a yet further aspect, R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6-membered heteroaryl substituted with 1 group selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO2(C1-C4 alkyl), and Cy². In an even further aspect, R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise an unsubstituted 6-membered heteroaryl. i. R³⁰ GROUPS In one aspect, R³⁰ is selected from hydrogen and C1-C4 alkyl. In a further aspect, R³⁰ is selected from hydrogen, methyl, ethyl, propyl, and isopropyl. In a further aspect, R³⁰ is selected from hydrogen, methyl, and ethyl. In a still further aspect, R³⁰ is selected from hydrogen and ethyl. In yet a further aspect, R³⁰ is selected from hydrogen and methyl. In various aspects, R³⁰ is C1-C4 alkyl. In a further aspect, R³⁰ is selected from methyl, ethyl, propyl, and isopropyl. In a further aspect, R³⁰ is selected from methyl and ethyl. In a still further aspect, R³⁰ is ethyl. In yet a further aspect, R³⁰ is methyl. In various aspects, R³⁰ is hydrogen. j. R³² GROUPS In one aspect, R³² is selected from hydrogen and C1-C4 alkyl. In a further aspect, R³² is selected from hydrogen, methyl, ethyl, propyl, and isopropyl. In a further aspect, R³² is selected from hydrogen, methyl, and ethyl. In a still further aspect, R³² is selected from hydrogen and ethyl. In yet a further aspect, R³² is selected from hydrogen and methyl. In various aspects, R³² is C1-C4 alkyl. In a further aspect, R³² is selected from methyl, ethyl, propyl, and isopropyl. In a further aspect, R³² is selected from methyl and ethyl. In a still further aspect, R³² is ethyl. In yet a further aspect, R³² is methyl. In various aspects, R³² is hydrogen. k. CY¹ GROUPS In one aspect, Cy¹ is selected from a C3-C10 cycloalkyl, C2-C9 heterocycloalkyl, C6- C10 aryl, and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, Cy¹ is selected from a C3-C10 cycloalkyl, C2-C9 heterocycloalkyl, C6-C10 aryl, and C2-C10 heteroaryl, and is substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a yet further aspect, Cy¹ is selected from a C3-C10 cycloalkyl, C2-C9 heterocycloalkyl, C6-C10 aryl, and C2-C10 heteroaryl, and is substituted with 0 or 1 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a still further aspect, Cy¹ is selected from a C3-C10 cycloalkyl, C2-C9 heterocycloalkyl, C6-C10 aryl, and C2-C10 heteroaryl, and is monosubstituted with a group selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO2(C1-C4 alkyl), and Cy². In an even further aspect, Cy¹ is selected from a C3-C10 cycloalkyl, C2-C9 heterocycloalkyl, C6-C10 aryl, and C2-C10 heteroaryl, and is unsubstituted. In various aspects, Cy¹ is selected from a C3-C10 cycloalkyl and a C2-C9 heterocycloalkyl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, Cy¹ is selected from a C3-C10 cycloalkyl and a C2-C9 heterocycloalkyl, and is substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a yet further aspect, Cy¹ is selected from a C3-C10 cycloalkyl and aC2- C9 heterocycloalkyl, and is substituted with 0 or 1 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a still further aspect, Cy¹ is selected from a C3-C10 cycloalkyl and a C2- C9 heterocycloalkyl, and is monosubstituted with a group selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In an even further aspect, Cy¹ is selected from a C3-C10 cycloalkyl and a C2-C9 heterocycloalkyl, and is unsubstituted. In various aspects, Cy¹ is a C3-C10 cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, Cy¹ is a C3-C10 cycloalkyl substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒ NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a yet further aspect, Cy¹ is a C3-C10 cycloalkyl substituted with 0 or 1 group selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a still further aspect, Cy¹ is a C3-C10 cycloalkyl monosubstituted with a group selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO2(C1-C4 alkyl), and Cy². In an even further aspect, Cy¹ is an unsubstituted C3-C10 cycloalkyl. In various aspects, Cy¹ is a C2-C9 heterocycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, Cy¹ is a C2-C9 heterocycloalkyl substituted with 0, 1, or 2 groups independently selected from halogen, ‒ CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a yet further aspect, Cy¹ is a C2-C9 heterocycloalkyl substituted with 0 or 1 group selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO2(C1-C4 alkyl), and Cy². In a still further aspect, Cy¹ is a C2-C9 heterocycloalkyl monosubstituted with a group selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In an even further aspect, Cy¹ is an unsubstituted C2-C9 heterocycloalkyl. In various aspects, Cy¹ is a 2,3-dihydrobenzo[b][1,4]dioxinyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, Cy¹ is a 2,3- dihydrobenzo[b][1,4]dioxinyl substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a yet further aspect, Cy¹ is a 2,3-dihydrobenzo[b][1,4]dioxinyl substituted with 0 or 1 group selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a still further aspect, Cy¹ is a 2,3-dihydrobenzo[b][1,4]dioxinyl monosubstituted with a group selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In an even further aspect, Cy¹ is an unsubstituted 2,3-dihydrobenzo[b][1,4]dioxinyl. In various aspects, Cy¹ is selected from C6-C10 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a further aspect, Cy¹ is selected from C6-C10 aryl and C2-C10 heteroaryl, and is substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒ NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a yet further aspect, Cy¹ is selected from C6-C10 aryl and C2-C10 heteroaryl, and is substituted with 0 or 1 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a still further aspect, Cy¹ is selected from C6-C10 aryl and C2-C10 heteroaryl, and is monosubstituted with a group selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO2(C1-C4 alkyl), and Cy². In an even further aspect, Cy¹ is selected from C6-C10 aryl and C2-C10 heteroaryl, and is unsubstituted. In various aspects, Cy¹ is a C6-C10 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a further aspect, Cy¹ is a C6-C10 aryl substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒ NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a yet further aspect, Cy¹ is a C6-C10 aryl substituted with 0 or 1 group selected from halogen, ‒CN, ‒ NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a still further aspect, Cy¹ is a C6-C10 aryl, and is monosubstituted with a group selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO2(C1-C4 alkyl), and Cy². In an even further aspect, Cy¹ is an unsubstituted C6-C10 aryl. In various aspects, Cy¹ is a phenyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO2(C1-C4 alkyl), and Cy². In a further aspect, Cy¹ is a phenyl substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a yet further aspect, Cy¹ is a phenyl substituted with 0 or 1 group selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a still further aspect, Cy¹ is phenyl, and is monosubstituted with a group selected from halogen, ‒CN, ‒ NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In an even further aspect, Cy¹ is an unsubstituted C6-C10 aryl. In various aspects, Cy¹ is a C2-C10 heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In a further aspect, Cy¹ is a C2-C10 heteroaryl substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒ NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a yet further aspect, Cy¹ is a C2-C10 heteroaryl substituted with 0 or 1 group selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In a still further aspect, Cy¹ is a C2-C10 heteroaryl monosubstituted with a group selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO₂(C1-C4 alkyl), and Cy². In an even further aspect, Cy¹ is an unsubstituted C2-C10 heteroaryl. l. CY² GROUPS In one aspect, Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, or 2 groups independently selected from halogen, ‒ CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a still further aspect, Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0 or 1 group selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a yet further aspect, Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is monosubstituted with a group independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In an even further aspect, Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is unsubstituted. In various aspects, Cy² is selected from a C3-C6 cycloalkyl and a C2-C5 heterocycloalkyl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, Cy² is selected from a C3-C6 cycloalkyl and a C2-C5 heterocycloalkyl, and is substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a still further aspect, Cy² is selected from a C3-C6 cycloalkyl and a C2-C5 heterocycloalkyl, and is substituted with 0 or 1 group selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a yet further aspect, Cy² is selected from a C3-C6 cycloalkyl and a C2-C5 heterocycloalkyl, and is monosubstituted with a group independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In an even further aspect, Cy² is selected from a C3- C6 cycloalkyl and a C2-C5 heterocycloalkyl, and is unsubstituted. In various aspects, Cy² is a C3-C6 cycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, Cy² is a C3-C6 cycloalkyl substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a still further aspect, Cy² is a C3- C6 cycloalkyl substituted with 0 or 1 group selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1- C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a yet further aspect, Cy² is a C3-C6 cycloalkyl monosubstituted with a group independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In an even further aspect, Cy² is an unsubstituted C3-C6 cycloalkyl. In various aspects, Cy² is a C2-C5 heterocycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. Examples of C2- C5 heterocycloalkyls include, but are not limited to, thiirane, oxirane, aziridine, thietane, azetidine, oxetane, pyrrolidine, imidazolidine, tetrahydrothiophene, tetrahydrofuran, piperidine, piperazine, thiane, and morpholine. In a further aspect, Cy² is a C2-C5 heterocycloalkyl, and is substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a still further aspect, Cy² is a C2-C5 heterocycloalkyl substituted with 0 or 1 group selected from halogen, ‒CN, ‒NH2, ‒OH, ‒ NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a yet further aspect, Cy² is a C2-C5 heterocycloalkyl monosubstituted with a group independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In an even further aspect, Cy² is an unsubstituted C2-C5 heterocycloalkyl. In various aspects, Cy² is selected from a C6 aryl and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, Cy² is selected from a C6 aryl and a C2-C5 heteroaryl, and is substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a still further aspect, Cy² is selected from a C6 aryl and a C2-C5 heteroaryl, and is substituted with 0 or 1 group selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a yet further aspect, Cy² is selected from a C6 aryl and a C2-C5 heteroaryl, and is monosubstituted with a group independently selected from halogen, ‒CN‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In an even further aspect, Cy² is selected from a C6 aryl and a C2-C5 heteroaryl, and is unsubstituted. In various aspects, Cy² is a C6 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a further aspect, Cy² is a C6 aryl substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒ NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a still further aspect, Cy² is a C6 aryl substituted with 0 or 1 group selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a yet further aspect, Cy² is a C6 aryl monosubstituted with a group independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In an even further aspect, Cy² is an unsubstituted C6 aryl. In various aspects, Cy² is a C2-C5 heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. Examples of C2- C5 heteroaryls include, but are not limited to, thiophene, furan, pyrrole, oxazole, isoxazole, isothiazole, pyridine, pyrimidine, pyridazine. In a further aspect, Cy² is a C2-C5 heteroaryl substituted with 0, 1, or 2 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒ NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a still further aspect, Cy² is a C2-C5 heteroaryl substituted with 0 or 1 group selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In a yet further aspect, Cy² is a C2-C5 heteroaryl monosubstituted with a group independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl. In an even further aspect, Cy² is an unsubstituted C2-C5 heteroaryl. m. FURTHER EMBODIMENTS In one aspect, m is 0 and A is ‒SO2‒. In one aspect, m is 0, A is ‒SO₂‒, and Cy¹ is selected from a C3-C10 cycloalkyl and a C2-C9 heterocycloalkyl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1- C4 alkyl), and Cy². In one aspect, m is 0, A is ‒SO2‒, and Cy¹ is a C2-C9 heterocycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In one aspect, m is 0, A is ‒SO₂‒, and Cy¹ is a 2,3-dihydrobenzo[b][1,4]dioxinyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In one aspect, m is 0, A is ‒SO₂‒, and Cy¹ is selected from a C6-C10 aryl and a C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒ CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In one aspect, m is 0, A is ‒SO2‒, and Cy¹ is a C6-C10 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1- C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². In one aspect, m is 0, A is ‒SO₂‒, and Cy¹ is phenyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². In one aspect, the compound has a structure represented by a formula: or a pharmaceutically acceptable salt thereof, wherein R^20a, R^20b, R^20c, R^20d, R^20e, Z¹, R^21a, R^21b, R^21c, Z², Z², R^21a, and R^21b are as defined herein. 2. EXEMPLARY COMPOUNDS In one aspect, a compound can be present as one or more of the following structures: or a pharmaceutically acceptable salt thereof. In one aspect, a compound can be present as one or more of the following structures: or a pharmaceutically acceptable salt thereof. 3. PROPHETIC EXAMPLE COMPOUNDS The following compound examples are prophetic, and can be prepared using the synthesis methods described herein below and other general methods as needed as would be known to one skilled in the art. It is anticipated that the prophetic compounds would be capable of inducing the degradation of proteins (e.g., KDM4B, VCL) relevant to the treatment of various cancers as further detailed herein, and such activity can be determined using the assay methods described herein below. Thus in one aspect, a compound is: or a pharmaceutically acceptable salt thereof. It is contemplated that one or more compounds can optionally be omitted from the disclosed invention. It is understood that the disclosed compounds can be used in connection with the disclosed methods, compositions, kits, and uses. It is understood that pharmaceutical acceptable derivatives of the disclosed compounds can be used also in connection with the disclosed methods, compositions, kits, and uses. The pharmaceutical acceptable derivatives of the compounds can include any suitable derivative, such as pharmaceutically acceptable salts as discussed below, isomers, radiolabeled analogs, tautomers, and the like. C. METHODS OF MAKING A COMPOUND The compounds of this invention can be prepared by employing reactions as shown in the following schemes, in addition to other standard manipulations that are known in the literature, exemplified in the experimental sections or clear to one skilled in the art. For clarity, examples having a single substituent are shown where multiple substituents are allowed under the definitions disclosed herein. Reactions used to generate the compounds of this invention are prepared by employing reactions as shown in the following Reaction Schemes, as described and exemplified below. In certain specific examples, the disclosed compounds can be prepared by Routes I-IV, as described and exemplified below. The following examples are provided so that the invention might be more fully understood, are illustrative only, and should not be construed as limiting. 1. ROUTE I In one aspect, the compounds disclosed herein can be prepared as shown below. SCHEME 1A. Compounds are represented in generic form, wherein X is halogen, each of PG¹ and PG² is individually an oxygen protecting group, PG³ is an amine protecting group, and each of R and R’ is independently selected from hydrogen, C1-C4 alkyl, or together comprise a 5- membered heterocycle, and with other substituents as noted in compound descriptions elsewhere herein. A more specific example is set forth below. SCHEME 1B. In one aspect, compounds of type 1.10, and similar compounds, can be prepared according to reaction Scheme 1B above. Thus, compounds of type 1.8 can be prepared by a coupling reaction between an aryl halide, e.g., 1.6 as shown above, and an appropriate boronic acid or ester, e.g., 1.7 as shown above. Appropriate aryl halides and appropriate boronic acids or esters are commercially available or prepared by methods known to one skilled in the art. The coupling reaction is carried out in the presence of an appropriate catalyst, e.g., bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane, and an appropriate base, e.g., potassium phosphate tribasic, in an appropriate solvent, e.g., dioxane/water, at an appropriate temperature, e.g., 110 °C, for an appropriate period of time, e.g., 12 hours. Compounds of type 1.9 can be prepared by deprotection and subsequent reduction of an appropriate substituted bisprotected pyridine- 2,6-diol, e.g., 1.8 as shown above. The deprotection and reduction is carried out under hydrogen gas at an appropriate pressure, e.g., 0.5 Mpa, in the presences on an appropriate catalyst, e.g., palladium on carbon, in an appropriate solvent, e.g., tetrahydrofuran (THF) and isopropyl alcohol (IPA) (3:1), at an appropriate temperature, e.g., 50 °C, for an appropriate period of time, e.g., 12h. Compounds of type 1.10 can be prepared by deprotection of an appropriate protected amine, e.g.1.9 as shown above. The deprotection is carried out in the presence of an appropriate cleavage agent, e.g., hydrogen chloride, in an appropriate solvent, e.g., ethyl acetate, at an appropriate temperature, e.g., 25 °C, for an appropriate period of time, e.g., 2 hours. As can be appreciated by one skilled in the art, the above reactions provide an example of a generalized approach wherein compounds similar in structure to the specific reactants above (compounds similar to compounds of type 1.1, 1.2, 1.3, and 1.4), can be substituted in the reaction to provide compounds similar to Formula 1.5. 2. ROUTE 2 In one aspect, the compounds disclosed herein can be prepared as shown below. SCHEME 2A. Compounds are represented in generic form with substituents as noted in compound descriptions elsewhere herein. A more specific example is set forth below. SCHEME 2B. In one aspect, compounds of type 2.6, and similar compounds, can be prepared according to reaction Scheme 2B above. Thus, compounds of type 2.6 can be prepared by coupling an appropriate amine, e.g., 2.4 as shown above, and an appropriate sulfonic chloride or acyl chloride, e.g., 2.5 as shown above. Appropriate sulfonic chlorides or acyl chlorides are commercially available or prepared by methods known to one skilled in the art. The coupling reaction is carried out in the presence of an appropriate base, e.g., triethyl amine, in an appropriate solvent, e.g., dimethylformamide (DMF), at an appropriate temperature, e.g., room temperature, for an appropriate period of time, e.g., 18 hours. As can be appreciated by one skilled in the art, the above reactions provide an example of a generalized approach wherein compounds similar in structure to the specific reactants above (compounds similar to compounds of type 2.1 and 2.2), can be substituted in the reaction to provide compounds similar to Formula 2.3. 3. ROUTE 3 In one aspect, the compounds disclosed herein can be prepared as shown below. SCHEME 3A. Compounds are represented in generic form, wherein X is a halogen and each of R and R’ is independently selected from hydrogen, C1-C4 alkyl, or together comprise a 5-membered heterocycle, and with other substituents as noted in compound descriptions elsewhere herein. A more specific example is set forth below. SCHEME 3B. Br In one aspect, compounds of type 3.6, and similar compounds, can be prepared according to reaction Scheme 3B above. Thus, compounds of type 3.6 can be prepared by coupling an appropriate aryl halide, e.g., 3.4 as shown above, and an appropriate boronic acid, e.g., 3.5 as shown above. Appropriate boronic acids are commercially available or prepared by methods known to one skilled in the art. The coupling reaction is carried out in the presence of an appropriate catalyst, e.g., added methanesulfonato(2-dicyclohexylphosphino-3,6-dimethoxy- 2',4',6'-tri-i-propyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (BrettPhos Pd Gen 3), in the presence of an appropriate base, e.g., cesium carbonate, in an appropriate solvent, e.g., 1,4 dioxane, at an appropriate temperature, e.g., 105 °C, for an appropriate period of time, e.g., 18 hours. As can be appreciated by one skilled in the art, the above reactions provide an example of a generalized approach wherein compounds similar in structure to the specific reactants above (compounds similar to compounds of type 3.1 and 3.2), can be substituted in the reaction to provide compounds similar to Formula 3.3. 4. ROUTE 4 In one aspect, the compounds disclosed herein can be prepared as shown below. SCHEME 4A. Compounds are represented in generic form, wherein X is a halogen, and with other substituents as noted in compound descriptions elsewhere herein. A more specific example is set forth below. SCHEME 4B. In one aspect, compounds of type 4.6, and similar compounds, can be prepared according to reaction Scheme 4B above. Thus, compounds of type 4.6 can be prepared by coupling an appropriate aryl halide, e.g., 4.4 as shown above, and an appropriate amine, e.g., 4.5 as shown above. Appropriate amines are commercially available or prepared by methods known to one skilled in the art. The coupling reaction is carried out in the presence of an appropriate catalyst, e.g., (2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2′-amino-1,1′- biphenyl)]palladium(II) methanesulfonate (RuPhos Pd Gen 3), in the presence of an appropriate base, e.g., cesium carbonate, in an appropriate solvent, e.g., 1,4-dioxane, at an appropriate temperature, e.g., 105 °C, for an appropriate period of time, e.g., 18 hours. As can be appreciated by one skilled in the art, the above reactions provide an example of a generalized approach wherein compounds similar in structure to the specific reactants above (compounds similar to compounds of type 4.1 and 4.2), can be substituted in the reaction to provide compounds similar to Formula 4.3. D. PHARMACEUTICAL COMPOSITIONS In one aspect, disclosed are pharmaceutical compositions comprising an effective amount of a disclosed compound, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. Thus, in one aspect, disclosed are pharmaceutical compositions comprising an effective amount of a compound having a structure represented by a formula: wherein m is selected from 0 and 1; wherein A is selected from ‒SO₂‒ and ‒C(O)‒; and wherein Cy¹ is selected from a C3-C10 cycloalkyl, a C2-C9 heterocycloalkyl, a C6-C10 aryl, and a C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1- C4 alkyl), and Cy²; wherein R¹⁰ is selected from hydrogen and C1-C4 alkyl; and wherein Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒ CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. In various aspects, the compounds and compositions of the invention can be administered in pharmaceutical compositions, which are formulated according to the intended method of administration. The compounds and compositions described herein can be formulated in a conventional manner using one or more physiologically acceptable carriers or excipients. For example, a pharmaceutical composition can be formulated for local or systemic administration, e.g., administration by drops or injection into the ear, insufflation (such as into the ear), intravenous, topical, or oral administration. The nature of the pharmaceutical compositions for administration is dependent on the mode of administration and can readily be determined by one of ordinary skill in the art. In various aspects, the pharmaceutical composition is sterile or sterilizable. The therapeutic compositions featured in the invention can contain carriers or excipients, many of which are known to skilled artisans. Excipients that can be used include buffers (for example, citrate buffer, phosphate buffer, acetate buffer, and bicarbonate buffer), amino acids, urea, alcohols, ascorbic acid, phospholipids, polypeptides (for example, serum albumin), EDTA, sodium chloride, liposomes, mannitol, sorbitol, water, and glycerol. The nucleic acids, polypeptides, small molecules, and other modulatory compounds featured in the invention can be administered by any standard route of administration. For example, administration can be parenteral, intravenous, subcutaneous, or oral. A modulatory compound can be formulated in various ways, according to the corresponding route of administration. For example, liquid solutions can be made for administration by drops into the ear, for injection, or for ingestion; gels or powders can be made for ingestion or topical application. Methods for making such formulations are well known and can be found in, for example, Remington's Pharmaceutical Sciences, 18th Ed., Gennaro, ed., Mack Publishing Co., Easton, PA 1990. In various aspects, the disclosed pharmaceutical compositions comprise the disclosed compounds (including pharmaceutically acceptable salt(s) thereof) as an active ingredient, a pharmaceutically acceptable carrier, and, optionally, other therapeutic ingredients or adjuvants. The instant compositions include those suitable for oral, rectal, topical, and parenteral (including subcutaneous, intramuscular, and intravenous) administration, although the most suitable route in any given case will depend on the particular host, and nature and severity of the conditions for which the active ingredient is being administered. The pharmaceutical compositions can be conveniently presented in unit dosage form and prepared by any of the methods well known in the art of pharmacy. In various aspects, the pharmaceutical compositions of this invention can include a pharmaceutically acceptable carrier and a compound or a pharmaceutically acceptable salt of the compounds of the invention. The compounds of the invention, or pharmaceutically acceptable salts thereof, can also be included in pharmaceutical compositions in combination with one or more other therapeutically active compounds. The pharmaceutical carrier employed can be, for example, a solid, liquid, or gas. Examples of solid carriers include lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, and stearic acid. Examples of liquid carriers are sugar syrup, peanut oil, olive oil, and water. Examples of gaseous carriers include carbon dioxide and nitrogen. In preparing the compositions for oral dosage form, any convenient pharmaceutical media can be employed. For example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like can be used to form oral liquid preparations such as suspensions, elixirs and solutions; while carriers such as starches, sugars, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrating agents, and the like can be used to form oral solid preparations such as powders, capsules and tablets. Because of their ease of administration, tablets and capsules are the preferred oral dosage units whereby solid pharmaceutical carriers are employed. Optionally, tablets can be coated by standard aqueous or nonaqueous techniques A tablet containing the composition of this invention can be prepared by compression or molding, optionally with one or more accessory ingredients or adjuvants. Compressed tablets can be prepared by compressing, in a suitable machine, the active ingredient in a free-flowing form such as powder or granules, optionally mixed with a binder, lubricant, inert diluent, surface active or dispersing agent. Molded tablets can be made by molding in a suitable machine, a mixture of the powdered compound moistened with an inert liquid diluent. The pharmaceutical compositions of the present invention comprise a compound of the invention (or pharmaceutically acceptable salts thereof) as an active ingredient, a pharmaceutically acceptable carrier, and optionally one or more additional therapeutic agents or adjuvants. The instant compositions include compositions suitable for oral, rectal, topical, and parenteral (including subcutaneous, intramuscular, and intravenous) administration, although the most suitable route in any given case will depend on the particular host, and nature and severity of the conditions for which the active ingredient is being administered. The pharmaceutical compositions can be conveniently presented in unit dosage form and prepared by any of the methods well known in the art of pharmacy. Pharmaceutical compositions of the present invention suitable for parenteral administration can be prepared as solutions or suspensions of the active compounds in water. A suitable surfactant can be included such as, for example, hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof in oils. Further, a preservative can be included to prevent the detrimental growth of microorganisms. Pharmaceutical compositions of the present invention suitable for injectable use include sterile aqueous solutions or dispersions. Furthermore, the compositions can be in the form of sterile powders for the extemporaneous preparation of such sterile injectable solutions or dispersions. In all cases, the final injectable form must be sterile and must be effectively fluid for easy syringability. The pharmaceutical compositions must be stable under the conditions of manufacture and storage; thus, preferably should be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol and liquid polyethylene glycol), vegetable oils, and suitable mixtures thereof. Pharmaceutical compositions of the present invention can be in a form suitable for topical use such as, for example, an aerosol, cream, ointment, lotion, dusting powder, mouth washes, gargles, and the like. Further, the compositions can be in a form suitable for use in transdermal devices. These formulations can be prepared, utilizing a compound of the invention, or pharmaceutically acceptable salts thereof, via conventional processing methods. As an example, a cream or ointment is prepared by mixing hydrophilic material and water, together with about 5 wt% to about 10 wt% of the compound, to produce a cream or ointment having a desired consistency. In addition to the aforementioned carrier ingredients, the pharmaceutical formulations described above can include, as appropriate, one or more additional carrier ingredients such as diluents, buffers, flavoring agents, binders, surface-active agents, thickeners, lubricants, preservatives (including anti-oxidants) and the like. Furthermore, other adjuvants can be included to render the formulation isotonic with the blood of the intended recipient. Compositions containing a compound of the invention, and/or pharmaceutically acceptable salts thereof, can also be prepared in powder or liquid concentrate form. In a further aspect, an effective amount is a therapeutically effective amount. In a still further aspect, an effective amount is a prophylactically effective amount. In a further aspect, the pharmaceutical composition is administered to a mammal. In a still further aspect, the mammal is a human. In an even further aspect, the human is a patient. In a further aspect, the pharmaceutical composition is used for inducing the degradation of proteins (e.g., KDM4B, VCL) that are relevant to cancer. The disclosed compounds and compositions can be useful in the treatment of a variety of different cancers including, but not limited to, a sarcoma, a carcinoma, a hematological cancer, a solid tumor, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, non-small cell lung carcinoma, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, melanoma, glioma, leukemia, lymphoma, chronic myeloproliferative disorder, myelodysplastic syndrome, myeloproliferative neoplasm, and plasma cell neoplasm (myeloma).. It is understood that the disclosed compositions can be prepared from the disclosed compounds. It is also understood that the disclosed compositions can be employed in the disclosed methods of using. E. METHODS OF DEGRADING A TARGET PROTEIN IN A CELL In one aspect, disclosed are methods of degrading a target protein (e.g., KDM4B, VCL) in a cell, the method comprising contacting the cell with an effective amount of a disclosed compound or a pharmaceutically acceptable salt thereof. Thus, in one aspect, disclosed are methods of degrading a target protein in a cell, the method comprising contacting the cell with an effective amount of a compound having a structure represented by a formula: wherein m is selected from 0 and 1; wherein A is selected from ‒SO₂‒ and ‒C(O)‒; and wherein Cy¹ is selected from a C3-C10 cycloalkyl, a C2-C9 heterocycloalkyl, a C6-C10 aryl, and a C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1- C4 alkyl), and Cy²; wherein R¹⁰ is selected from hydrogen and C1-C4 alkyl; and wherein Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒ CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, or a pharmaceutically acceptable salt thereof. In various aspects, the target protein is KDM4B or VCL. In various aspects, the cell is mammalian. In a further aspect, the cell is human. In various aspects, the cell has been isolated from a mammal prior to the contacting step. In various aspects, the contacting is ex vivo. In various aspects, the contacting is in vitro. In various aspects, contacting is via administration to a mammal. In a further aspect, the mammal has been diagnosed with a need for degrading the target protein prior to the administering step. In a still further aspect, the mammal has been diagnosed with a need for treatment of a cancer related to activity of the target protein prior to the administering step. F. METHODS OF DEGRADING A TARGET PROTEIN IN A SUBJECT In one aspect, disclosed are methods of degrading a target protein (e.g., KDM4B, VCL) in a subject, the method comprising administering to the subject an effective amount of a disclosed compound or a pharmaceutically acceptable salt thereof. Thus, in one aspect, disclosed are methods of degrading a target protein in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound having a structure represented by a formula: wherein m is selected from 0 and 1; wherein A is selected from ‒SO₂‒ and ‒C(O)‒; and wherein Cy¹ is selected from a C3-C10 cycloalkyl, a C2-C9 heterocycloalkyl, a C6-C10 aryl, and a C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1- C4 alkyl), and Cy²; wherein R¹⁰ is selected from hydrogen and C1-C4 alkyl; and wherein Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒ CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, or a pharmaceutically acceptable salt thereof. In various aspects, the subject is a mammal. In a further aspect, the subject is a human. In various aspects, the subject has been diagnosed with a need for degrading the target protein prior to the administering step. In various aspects, the method further comprising identifying a subject in need of degradation of the target protein. G. METHODS OF TREATING A CANCER IN A SUBJECT In one aspect, disclosed are methods of treating a cancer in a subject, the method comprising administering to the subject an effective amount of a disclosed compound or a pharmaceutically acceptable salt thereof. Thus, in one aspect, disclosed are methods of treating a cancer in a subject, the method comprising administering to the subject an effective amount of a compound having a structure represented by a formula: wherein m is selected from 0 and 1; wherein A is selected from ‒SO2‒ and ‒C(O)‒; and wherein Cy¹ is selected from a C3-C10 cycloalkyl, a C2-C9 heterocycloalkyl, a C6-C10 aryl, and a C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1- C4 alkyl), and Cy²; wherein R¹⁰ is selected from hydrogen and C1-C4 alkyl; and wherein Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒ CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl,or a pharmaceutically acceptable salt thereof. In various aspects, the subject is a mammal. In a further aspect, the subject is a human. In various aspects, the subject has been diagnosed with a need for treatment of the cancer prior to the administering step. In various aspects, the method further comprising the step of identifying a subject in need of treatment of the cancer. In a further aspect, the effective amount is a therapeutically effective amount. In a further aspect, the effective amount is a prophylactically effective amount. In a further aspect, the cancer is associated with activity of a protein selected from KDM4B and VCL. In a further aspect, the cancer is selected from a sarcoma, a carcinoma, a hematological cancer, a solid tumor, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, non-small cell lung carcinoma, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, melanoma, glioma, leukemia, lymphoma, chronic myeloproliferative disorder, myelodysplastic syndrome, myeloproliferative neoplasm, and plasma cell neoplasm (myeloma). In a further aspect, the cancer is leukemia. H. ADDITIONAL METHODS OF USING THE COMPOUNDS The compounds and pharmaceutical compositions of the invention are useful in inducing the degradation of proteins (e.g., KDM4B, VCL) relevant to cancer. Examples of cancer include, but are not limited to, a sarcoma, a carcinoma, a hematological cancer, a solid tumor, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, non-small cell lung carcinoma, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, melanoma, glioma, leukemia, lymphoma, chronic myeloproliferative disorder, myelodysplastic syndrome, myeloproliferative neoplasm, and plasma cell neoplasm (myeloma). To treat or control the condition, the compounds and pharmaceutical compositions comprising the compounds are administered to a subject in need thereof, such as a vertebrate, e.g., a mammal, a fish, a bird, a reptile, or an amphibian. The subject can be a human, non- human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig, or rodent. The term does not denote a particular age or sex. Thus, adult and newborn subjects, as well as fetuses, whether male or female, are intended to be covered. The subject is preferably a mammal, such as a human. Prior to administering the compounds or compositions, the subject can be diagnosed with a need for treatment of cancer (e.g., a sarcoma, a carcinoma, a hematological cancer, a solid tumor, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, non-small cell lung carcinoma, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, melanoma, glioma, leukemia, lymphoma, chronic myeloproliferative disorder, myelodysplastic syndrome, myeloproliferative neoplasm, and plasma cell neoplasm (myeloma)). The compounds or compositions can be administered to the subject according to any method. Such methods are well known to those skilled in the art and include, but are not limited to, oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, intravaginal administration, ophthalmic administration, intraaural administration, intracerebral administration, rectal administration, sublingual administration, buccal administration and parenteral administration, including injectable such as intravenous administration, intra-arterial administration, intramuscular administration, and subcutaneous administration. Administration can be continuous or intermittent. A preparation can be administered therapeutically; that is, administered to treat an existing disease or condition. A preparation can also be administered prophylactically; that is, administered for prevention of cancer. The therapeutically effective amount or dosage of the compound can vary within wide limits. Such a dosage is adjusted to the individual requirements in each particular case including the specific compound(s) being administered, the route of administration, the condition being treated, as well as the patient being treated. In general, in the case of oral or parenteral administration to adult humans weighing approximately 70 Kg or more, a daily dosage of about 10 mg to about 10,000 mg, preferably from about 200 mg to about 1,000 mg, should be appropriate, although the upper limit may be exceeded. The daily dosage can be administered as a single dose or in divided doses, or for parenteral administration, as a continuous infusion. Single dose compositions can contain such amounts or submultiples thereof of the compound or composition to make up the daily dose. The dosage can be adjusted by the individual physician in the event of any contraindications. Dosage can vary, and can be administered in one or more dose administrations daily, for one or several days. 1. MANUFACTURE OF A MEDICAMENT In one aspect, the invention relates to a method for the manufacture of a medicament for inducing the degradation of proteins (e.g., KDM4B, VCL) relevant to cancer in a subject in need thereof, the method comprising combining a therapeutically effective amount of a disclosed compound or product of a disclosed method with a pharmaceutically acceptable carrier or diluent. Also disclosed herein is the use of the disclosed compounds or a pharmaceutically acceptable salt thereof, together with a compound or agent known for inducing the degradation of proteins (e.g., KDM4B, VCL) relevant to cancer, in the manufacture of a medicament. In one aspect, for example, when the subject has a cancer, disclosed is the use of the disclosed compounds or a pharmaceutically acceptable salt thereof along with a compound known for treating cancer. In one aspect, the manufacture of the medicament can comprise co-formulating or co- packaging the disclosed compounds, or a pharmaceutically acceptable salt thereof, together with a chemotherapeutic agent. Non-limiting of chemotherapeutic agents include, but are not limited to, alkylating agents, antimetabolite agents, antineoplastic antibiotic agents, mitotic inhibitor agents, and mTor inhibitor agents. In various aspects, the method for the manufacture of a medicament comprises combining a therapeutically effective amount of the disclosed compounds, or a pharmaceutically acceptable salt thereof, with a pharmaceutically acceptable carrier or diluent and/or with a compound known for treating cancer. In a further aspect, disclosed is a method for the manufacture of a medicament for treating cancer, the method comprising combining a therapeutically effective amount of a disclosed compounds or a pharmaceutically acceptable salt thereof with a therapeutically effective amount of a compound known for treating cancer, together with a pharmaceutically acceptable carrier or diluent. 2. USE OF COMPOUNDS AND COMPOSITIONS In one aspect, the invention relates to the use of a disclosed compound, a disclosed composition, or a product of a disclosed method. In a further aspect, a use relates to the manufacture of a medicament for inducing the degradation of proteins (e.g., KDM4B, VCL) relevant to cancer. In a still further aspect, a use relates to the manufacture of a medicament for treating cancer (e.g., a sarcoma, a carcinoma, a hematological cancer, a solid tumor, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, non-small cell lung carcinoma, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, melanoma, glioma, leukemia, lymphoma, chronic myeloproliferative disorder, myelodysplastic syndrome, myeloproliferative neoplasm, plasma cell neoplasm (myeloma)). The compounds and pharmaceutical compositions of the invention are useful in treating or controlling disorders associated with overexpression of KDM4B. Also provided are the uses of the disclosed compounds and products. In one aspect, the invention relates to use of at least one disclosed compound, or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof. In a further aspect, the compound used is a product of a disclosed method of making. In a further aspect, the use relates to a process for preparing a pharmaceutical composition comprising a therapeutically effective amount of a disclosed compound or a product of a disclosed method of making, or a pharmaceutically acceptable salt, solvate, or polymorph thereof, for use as a medicament. In a further aspect, the use relates to a process for preparing a pharmaceutical composition comprising a therapeutically effective amount of a disclosed compound or a product of a disclosed method of making, or a pharmaceutically acceptable salt, solvate, or polymorph thereof, wherein a pharmaceutically acceptable carrier is intimately mixed with a therapeutically effective amount of the compound or the product of a disclosed method of making. It is understood that the disclosed uses can be employed in connection with the disclosed compounds, products of disclosed methods of making, methods, compositions, and kits. In a further aspect, the invention relates to the use of a disclosed compound or a disclosed product in the manufacture of a medicament for the treatment of a disorder associated with overexpression of KDM4B. 3. KITS In one aspect, disclosed are kits comprising a disclosed compound, or a pharmaceutically acceptable salt thereof, and one or more selected from: (a) an agent known to treat a cancer; (b) instructions for administering the compound in connection with treating a cancer; and (c) instructions for treating a cancer. Thus, in one aspect, disclosed are kits comprising a compound having a structure represented by a formula: , wherein m is selected from 0 and 1; wherein A is selected from ‒SO2‒ and ‒C(O)‒; and wherein Cy¹ is selected from a C3-C10 cycloalkyl, a C2-C9 heterocycloalkyl, a C6-C10 aryl, and a C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1- C4 alkyl), and Cy²; wherein R¹⁰ is selected from hydrogen and C1-C4 alkyl; and wherein Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒ CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, or a pharmaceutically acceptable salt thereof, and one or more selected from: (a) an agent known to treat a cancer; (b) instructions for administering the compound in connection with treating a cancer; and (c) instructions for treating a cancer. In various aspects, the agent known to treat a cancer is a chemotherapeutic agent. In a further aspect, the chemotherapeutic agent is selected from an alkylating agent, an antimetabolite agent, an antineoplastic antibiotic agent, a mitotic inhibitor agent, and a mTor inhibitor agent. In a still further aspect, the antineoplastic antibiotic agent is selected from doxorubicin, mitoxantrone, bleomycin, daunorubicin, dactinomycin, epirubicin, idarubicin, plicamycin, mitomycin, pentostatin, and valrubicin, or a pharmaceutically acceptable salt thereof. In a yet further aspect, the antimetabolite agent is selected from gemcitabine, 5- fluorouracil, capecitabine, hydroxyurea, mercaptopurine, pemetrexed, fludarabine, nelarabine, cladribine, clofarabine, cytarabine, decitabine, pralatrexate, floxuridine, methotrexate, and thioguanine, or a pharmaceutically acceptable salt thereof. In an even further aspect, the alkylating agent is selected from carboplatin, cisplatin, cyclophosphamide, chlorambucil, melphalan, carmustine, busulfan, lomustine, dacarbazine, oxaliplatin, ifosfamide, mechlorethamine, temozolomide, thiotepa, bendamustine, and streptozocin, or a pharmaceutically acceptable salt thereof. In an even still further aspect, the mitotic inhibitor agent is selected from irinotecan, topotecan, rubitecan, cabazitaxel, docetaxel, paclitaxel, etopside, vincristine, ixabepilone, vinorelbine, vinblastine, and teniposide, or a pharmaceutically acceptable salt thereof. In an even yet further aspect, mTor inhibitor agent is selected from everolimus, siroliumus, and temsirolimus, or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof. In various aspects, the compound and the agent known to treat cancer are co-packaged. In various further aspects, a disclosed compound or a pharmaceutically-acceptable salt thereof, the instructions for the use thereof (when present) and/or a combination therapy including a compound known for treating the target condition can be co-packaged and/or co- formulated. In a still further aspect, the compound or pharmaceutically-acceptable salt thereof, the instructions (when present), and/or the compound known for treating the target condition are not co-packaged. The kits can also comprise compounds and/or products co-packaged, co-formulated, and/or co-delivered with other components. For example, a drug manufacturer, a drug reseller, a physician, a compounding shop, or a pharmacist can provide a kit comprising a disclosed compound and/or product and another component for delivery to a patient. It is understood that the disclosed kits can be prepared from the disclosed compounds and pharmaceutical formulations. It is also understood that the disclosed kits can be employed in connection with the disclosed methods of using the compounds and pharmaceutical formulations. In a further aspect, the kit further comprises a plurality of dosage forms, the plurality comprising one or more doses; wherein each dose comprises an effective amount of the compound and the agent. In an even further aspect, each dose of the compound and the agent are co-packaged. In a still further aspect, each dose of the compound and the agent are co- formulated. 4. SUBJECTS In various aspects, the subject of the herein disclosed methods is a vertebrate, e.g., a mammal. Thus, the subject of the herein disclosed methods can be a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig or rodent. The term does not denote a particular age or sex. Thus, adult and newborn subjects, as well as fetuses, whether male or female, are intended to be covered. A patient refers to a subject afflicted with a disease or disorder. The term “patient” includes human and veterinary subjects. In some aspects of the disclosed methods, the subject has been diagnosed with a need for treatment prior to the administering step. In some aspects of the disclosed method, the subject has been diagnosed with a disorder of uncontrolled cellular proliferation prior to the administering step. In some aspects of the disclosed methods, the subject has been identified with a need for treatment prior to the administering step. In one aspect, a subject can be treated prophylactically with a compound or composition disclosed herein, as discussed herein elsewhere. a. DOSAGE Toxicity and therapeutic efficacy of the agents and pharmaceutical compositions described herein can be determined by standard pharmaceutical procedures, using either cells in culture or experimental animals to determine the LD₅₀ (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and can be expressed as the ratio LD50/ED50. Data obtained from cell culture assays and further animal studies can be used in formulating a range of dosage for use in humans. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED50 with little or no toxicity, and with little or no adverse effect on a human's ability to hear. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. For any agents used in the methods described herein, the therapeutically effective dose can be estimated initially from cell culture assays. A dose can be formulated in animal models to achieve a circulating plasma concentration range that includes the IC50 (that is, the concentration of the test compound which achieves a half- maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Exemplary dosage amounts of a differentiation agent are at least from about 0.01 to 3000 mg per day, e.g., at least about 0.00001, 0.0001, 0.001, 0.01, 0.1, 1, 2, 5, 10, 25, 50, 100, 200, 500, 1000, 2000, or 3000 mg per kg per day, or more. The formulations and routes of administration can be tailored to the disease or disorder being treated, and for the specific human being treated. For example, a subject can receive a dose of the agent once or twice or more daily for one week, one month, six months, one year, or more. The treatment can continue indefinitely, such as throughout the lifetime of the human. Treatment can be administered at regular or irregular intervals (once every other day or twice per week), and the dosage and timing of the administration can be adjusted throughout the course of the treatment. The dosage can remain constant over the course of the treatment regimen, or it can be decreased or increased over the course of the treatment. In various aspects, the dosage facilitates an intended purpose for both prophylaxis and treatment without undesirable side effects, such as toxicity, irritation or allergic response. Although individual needs may vary, the determination of optimal ranges for effective amounts of formulations is within the skill of the art. Human doses can readily be extrapolated from animal studies (Katocs et al., (1990) Chapter 27 in Remington's Pharmaceutical Sciences, 18th Ed., Gennaro, ed., Mack Publishing Co., Easton, PA). In general, the dosage required to provide an effective amount of a formulation, which can be adjusted by one skilled in the art, will vary depending on several factors, including the age, health, physical condition, weight, type and extent of the disease or disorder of the recipient, frequency of treatment, the nature of concurrent therapy, if required, and the nature and scope of the desired effect(s) (Nies et al., (1996) Chapter 3, In: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 9th Ed., Hardman et al., eds., McGraw-Hill, New York, NY). b. ROUTES OF ADMINISTRATION Also provided are routes of administering the disclosed compounds and compositions. The compounds and compositions of the present invention can be administered by direct therapy using systemic administration and/or local administration. In various aspects, the route of administration can be determined by a patient's health care provider or clinician, for example following an evaluation of the patient. In various aspects, an individual patient's therapy may be customized, e.g., the type of agent used, the routes of administration, and the frequency of administration can be personalized. Alternatively, therapy may be performed using a standard course of treatment, e.g., using pre-selected agents and pre-selected routes of administration and frequency of administration. Systemic routes of administration can include, but are not limited to, parenteral routes of administration, e.g., intravenous injection, intramuscular injection, and intraperitoneal injection; enteral routes of administration e.g., administration by the oral route, lozenges, compressed tablets, pills, tablets, capsules, drops (e.g., ear drops), syrups, suspensions and emulsions; rectal administration, e.g., a rectal suppository or enema; a vaginal suppository; a urethral suppository; transdermal routes of administration; and inhalation (e.g., nasal sprays). In various aspects, the modes of administration described above may be combined in any order. The foregoing description illustrates and describes the disclosure. Additionally, the disclosure shows and describes only the preferred embodiments but, as mentioned above, it is to be understood that it is capable to use in various other combinations, modifications, and environments and is capable of changes or modifications within the scope of the invention concepts as expressed herein, commensurate with the above teachings and/or the skill or knowledge of the relevant art. The embodiments described herein above are further intended to explain best modes known by applicant and to enable others skilled in the art to utilize the disclosure in such, or other, embodiments and with the various modifications required by the particular applications or uses thereof. Accordingly, the description is not intended to limit the invention to the form disclosed herein. Also, it is intended to the appended claims be construed to include alternative embodiments. All publications and patent applications cited in this specification are herein incorporated by reference, and for any and all purposes, as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. In the event of an inconsistency between the present disclosure and any publications or patent application incorporated herein by reference, the present disclosure controls. I. EXAMPLES The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how the methods and products claimed herein are made and evaluated, and are intended to be purely exemplary and are not intended to limit the scope of what the inventors regard as their invention. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.), but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in °C or is at ambient temperature, and pressure is at or near atmospheric. The Examples are provided herein to illustrate the invention, and should not be construed as limiting the invention in any way. 1. CHEMISTRY METHODS a. REPRESENTATIVE PROCEDURE FOR THE PREPARATION OF SMALL MOLECULES THAT RECOGNIZE KDM4 AND/OR VCL (COMPOUND 4) To a solution of Compound 1 (12 g, 40.24 mmol, 1 eq) in dioxane (120 mL) and H₂O (12 mL) was added 2,6-dibenzyloxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (18.47 g, 44.27 mmol, 1.1 eq), K₃PO₄ (25.63 g, 120.73 mmol, 3 eq) and cyclopentyl(diphenyl)phosphane;dichloromethane;dichloropalladium;iron (1.64 g, 2.01 mmol, 0.05 eq) under N₂, then the mixture was stirred at 110 °C for 12 hr under N₂. LC-MS showed the reaction was complete and the desired MS was detected. The reaction mixture was filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography on silica gel (Petroleum ether/Ethyl acetate=1/0 to 30/1). Compound 2 (20 g, crude) was obtained as yellow oil. ii. STEP 2 To a solution of Compound 2 (10 g, 19.66 mmol, 1 eq) in THF (300 mL) and IPA (100 mL) was added Pd/C (10.46 g, 4.92 mmol, 5% purity, 0.25 eq), then the mixture was stirred at 50 °C for 12 h under H2 (39.72 mg, 19.66 mmol, 1 eq) (0.5 Mpa). LC-MS showed that Compound 2 was consumed and the desired product MS was detected. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography on silica gel (Petroleum ether/Ethyl acetate=1/0 to 2/1). Compound 3 (2.6 g, crude) was obtained as white solid. iii. STEP 3 A solution of Compound 3 (2.6 g, 7.87 mmol, 1 eq) in HCl/EtOAc (4 M, 26.00 mL, 13.22 eq) was stirred at 25 °C for 2 h. LC-MS showed that Compound 3 was consumed and the desired product MS was detected. The reaction mixturewas concentrated under reduced pressure to give a residue. The residue was added to EtOAc (30 ml) and stirred at 25 °C for 1 h, then the mixture was filtered and the filter cake concentrated under reduced pressure to give the product, Compound 4 (2.01 g, 7.51 mmol, 95.42% yield, 99.647% purity, HCl) as a gray solid.¹H NMR (400 MHz, METHANOL-d₄) δ = 7.42 (d, J = 7.7 Hz, 1H), 7.36 - 7.29 (m, 2H), 4.62 (s, 4H), 3.94 (dd, J = 5.2, 11.4 Hz, 1H), 2.83 - 2.61 (m, 2H), 2.37 - 2.13 (m, 2H) LCMS (ESI+): m/z 231.1 (M+H). a. REPRESENTATIVE PROCEDURE A FOR THE PREPARATION OF PROTEIN DEGRADERS (COMPOUND NO.5)

3-(Isoindolin-5-yl)piperidine-2,6-dione (0.109 mmol, 1 equiv) was dissolved in DMF (1.09 mL, 0.1 M) then triethylamine (0.434 mmoL, 4 equiv) was added followed by 4- cyclohexylbenzenesulfonyl chloride (0.13 mmol, 1.2 equiv). The reaction mixture was allowed to stir at room temperature for 18hrs. UPLC showed the complete consumption of the starting material. The crude reaction mixture was filtered through Celite, rinsed with DMSO (0.5 mL), and purified by the Waters purification/analytical LC/UV/ELSD system and the gradient program started at 95% (0.1% formic acid in MilliQ H2O), changed to 90% (0.1% formic acid in Acetonitrile) over 14 min. Desired fractions were concentrated using a TurboVap® LV evaporator to afford 3-(2-((4-cyclohexylphenyl)sulfonyl)isoindolin-5- yl)piperidine-2,6-dione (30 mgs, 61.1%, purity >98%). b. REPRESENTATIVE PROCEDURE B FOR THE PREPARATION OF PROTEIN DEGRADERS (COMPOUND NO.70) 3-(2-((4-Bromophenyl)sulfonyl)isoindolin-5-yl)piperidine-2,6-dione (0.045 mmol, 1 eq) was dissolved in 1,4-dioxane (0.1M) then methanesulfonato(2-dicyclohexylphosphino-3,6- dimethoxy-2',4',6'-tri-i-propyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II) (BrettPhos Pd Gen 3) (0.0045 mmol, 0.1 eq), Cs₂CO₃ (0.134 mmol, 3 eq) and o-tolylboronic acid (0.067 mmol, 1.5 eq) were added. The reaction mixture was heated to 105 °C and stirred overnight. Crude reaction mixture was filtered through a plug of Celite and washed with EtOAc (5 mL). Filtrate was concentrated then taken up in DMSO and purified by the Waters purification/analytical LC/UV/ELSD system and the gradient program started at 95% (0.1% formic acid in MilliQ H₂O), changed to 90% (0.1% formic acid in Acetonitrile) over 14 min. Desired fractions were concentrated using a TurboVap^® LV evaporator to afford 3-2-((4- morpholinophenyl)sulfonyl)isoindolin-5-yl)piperidine-2,6-dione (12.4 mg, 60.5% yield, 98% purity, (M+1) = 461.4) c. REPRESENTATIVE PROCEDURE C FOR THE PREPARATION OF PROTEIN DEGRADERS (COMPOUND NO.83) 3-(2-((4-Bromophenyl)sulfonyl)isoindolin-5-yl)piperidine-2,6-dione (0.045 mmol, 1 eq) was dissolved in 1,4-dioxane (0.1M) then (2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′- biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate (RuPhos Pd Gen 3) (0.0045 mmol, 0.1 eq), Cs₂CO₃ (0.134 mmol, 3 eq) and morpholine (0.067 mmol, 1.5 eq) were added. The reaction mixture was heated to 105 °C and stirred overnight. Crude reaction mixture was filtered through a plug of Celite and washed with EtOAc (5 mL). Filtrate was concentrated then taken up in DMSO and purified by the Waters purification/analytical LC/UV/ELSD system and the gradient program started at 95% (0.1% formic acid in MilliQ H2O), changed to 90% (0.1% formic acid in Acetonitrile) over 14 min. Desired fractions were concentrated using a TurboVap^® LV evaporator to afford 3-2-((4- morpholinophenyl)sulfonyl)isoindolin-5-yl)piperidine-2,6-dione (1.7 mg, 8.4% yield, 100% purity, (M+1) = 456.4). 2. BIOLOGY METHODS a. CELL CULTURE Rhabdomyosarcoma (RH30, RH4), neuroblastoma (BE2C, SIMA, SKNAS, SKNSH), Ewing sarcoma (EW-8) and 786-O cell lines are maintained in RPMI1640 medium, supplemented with 10% FBS, 100 U/mL penicillin–streptomycin. KASUMI-1 cell line is maintained in RPMI1640 medium, supplemented with 20% FBS, 100 U/mL penicillin– streptomycin. SKNO-1 cell line is maintained in RPMI1640 medium, supplemented with 10% FBS, 100 U/mL penicillin–streptomycin, 10 ng/ml GM-CSF. CAKI-1 cell line is maintained in McCoy’s 5A medium supplemented with 10% FBS, 100 U/mL penicillin– streptomycin, 10 ng/ml GM-CSF. b. WESTERN BLOT Cells were lysed on ice using a lysis buffer (0.1 M Tris-HCl, pH 6.8, 200 mM dithiothreitol, 0.01% bromophenol blue, 4% sodium dodecyl sulfate and 20% glycerol). Samples were sonicated at 4 °C for 10 s, and then boiled at 95 °C for 10 min. Cell lysates were separated on 4–15% precast polyacrylamide gel and transferred to PVDF membranes pre-activated with methanol. Membranes were blocked in a solution of 5% milk in PBST buffer and incubated for 1 hour at room temperature and incubated overnight with primary antibodies at 4 °C under gentle horizontal shaking. The next day, membranes were washed with PBST buffer and incubated with anti-mouse or anti-rabbit HRP-conjugated secondary antibodies (1:5,000). Membranes were washed with PBST buffer, incubated with SuperSignal West Pico PLUS Chemiluminescent Substrate and developed using an Odyssey Fc Imaging System (LI-COR Corp.). KDM4A (Abclonal, A7953), KDM4B (Bethyl, A301- 478A), KDM4C (Abclonal, A8485), KDM4D (ProteinTech, 22591-1-AP), GAPDH (Cell Signaling, 3683S), α-Tubulin (Santa cruz, sc-69969), CRBN (CST, 71810S), VCL (Cell Signaling, 13901S), Flag M2 (SIGMA, 080M6035). 3. EVALUATION OF THE ABILITY OF EXEMPLARY COMPOUNDS TO INDUCE PROTEIN DEGRADATION A list of exemplary compounds is shown in Table 1 below. Compounds were prepared using the synthetic methods described herein. Table 1. The ability of the exemplary compounds to degrade KDM4B or vinculin was evaluated as detailed herein and the results are shown in Table 2 below. See also FIG.1, in which immunoblots for KDM4B protein after the treatment BE2C cells with molecular glue compounds (100 nM for 24 hours) are shown. Table 2. Co N Co N N/A = Not Tested  Immunoblots demonstrating how compound 6 degrades KDM4B in a time-, concentration-, and CRBN- dependent manner are shown in FIG.2A-C. Specifically, FIG. 2A shows immunoblots for KDM4B protein after the treatment of BE2C cells with increasing concentrations of compound 6 for 24 h. FIG.2B shows immunoblots for KDM4B protein after the treatment of BE2C cells with 100 nM of compound 6 over 48 h, and proteins were harvested at 0, 1, 2, 4, 8, 24, and 48 hours after treatment. FIG.2C shows immunoblots for KDM4B protein after the treatment of BE2C wild-type and CRBN knockout cells with compounds 6 for 24 h. Referring to FIG.3A and FIG.3B, compound 6 selectively targets KDM4B and degrades KDM4B in multiple cell lines. FIG.3A shows immunoblots for KDM4A-D proteins after the treatment of BE2C cells with 1 and 10 µM of compounds 6 for 24 h. FIG. 3B shows immunoblots for KDM4B protein after the treatment of neuroblastoma (BE2C, SIMA), rhabdomyosarcoma (RH30, RH4), leukemia (KASUMI-1, SKNO-1), Ewing sarcoma (EW-8) cells with 1 µM and 10 µM of compounds 6 for 24 h. Immunoblots demonstrating how compound 5 degrades vinculin in a time-, concentration-, and lenalidomide dependent manner are shown in FIG.4A-C. Specifically, FIG.4A shows imunoblots for vinculin protein after the treatment of CAKI-1 cells with increasing concentrations of compound 5 for 24 h. FIG.4B shows immunoblots for vinculin protein after the treatment of CAKI-1 cells with 1 µM compound 5 over 48 h, and proteins were harvested at 0, 1, 2, 4, 8, 24, and 48 hours after treatment. FIG.4C shows immunoblots for vinculin protein after the treatment of CAKI-1 cells with compound 5 for 24 h in the presence and absence of lenalidomide. Referring to FIG.5, immunoblots for vinculin protein after the treatment of kidney tumor cell lines (786-O, WiT49) and neuroblastoma cell lines (SKNAS, BE2C, SKNSH) cells with 1 and 10 µM of compounds 5 for 24 h are shown. It will be apparent to those skilled in the art that various modifications and variations can be made without departing from the scope or spirit of this disclosure. Other embodiments will be apparent to those skilled in the art from consideration of the specification and practice disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit being indicated by the following claims.  

Claims

CLAIMS What is claimed is: 1. A compound having a structure represented by a formula: , wherein m is selected from 0 and 1; wherein A is selected from ‒SO₂‒ and ‒C(O)‒; and wherein Cy¹ is selected from a C3-C10 cycloalkyl, a C2-C9 heterocycloalkyl, a C6-C10 aryl, and a C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO₂(C1-C4 alkyl), and Cy²; wherein R¹⁰ is selected from hydrogen and C1-C4 alkyl; and wherein Cy² is selected from a C3-C6 cycloalkyl, a C2-C5 heterocycloalkyl, a C6 aryl, and a C2-C5 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1, wherein m is 0. 3. The compound of claim 1 or claim 2, wherein A is ‒SO2‒. 4. The compound of any one of claims 1 to 3, wherein Cy¹ is selected from a C3-C10 cycloalkyl and a C2-C9 heterocycloalkyl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². 5. The compound of any one of claims 1 to 3, wherein Cy¹ is a C2-C9 heterocycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². 6. The compound of any one of claims 1 to 3, wherein Cy¹ is a 2,3- dihydrobenzo[b][1,4]dioxinyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1- C4 alkyl), and Cy². 7. The compound of any one of claims 1 to 3, wherein Cy¹ is selected from a C6-C10 aryl and a C2-C10 heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO₂(C1-C4 alkyl), and Cy². 8. The compound of any one of claims 1 to 3, wherein Cy¹ is a C6-C10 aryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1- C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². 9. The compound of any one of claims 1 to 3, wherein Cy¹ is a phenyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². 10. The compound of claim 1, wherein the compound has a structure represented by a formula: , or a pharmaceutically acceptable salt thereof. 11. The compound of claim 1, wherein the compound has a structure represented by a formula: wherein each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1- C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², provided that at least two of R^20a, R^20b, R^20c, R^20d, and R^20e is hydrogen, or wherein any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle, a 5-membered heterocycle, a 6-membered aryl, or a 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2- C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², or a pharmaceutically acceptable salt thereof. 12. The compound of claim 11, wherein each of R^20a, R^20b, R^20c, R^20d, and R^20e is independently selected from hydrogen, halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2- C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒ NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², provided that at least two of R^20a, R^20b, R^20c, R^20d, and R^20e is hydrogen. 13. The compound of claim 11, wherein any adjacent two of R^20a, R^20b, R^20c, R^20d, and R^20e is covalently bonded and, together with the intermediate atoms, comprise a 5-membered cycle, a 5-membered heterocycle, a 6-membered aryl, or a 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy². 14. The compound of claim 11, wherein the compound has a structure represented by a formula: or a pharmaceutically acceptable salt thereof. 15. The compound of claim 1, wherein the compound has a structure represented by a formula: R^21b R^21c Z¹ wherein Z¹ is selected from ‒O‒, ‒S‒, and ‒N(R³⁰)‒; wherein R³⁰ is selected from hydrogen and C1-C4 alkyl; wherein each of R^21a, R^21b, and R^21c is independently selected from hydrogen, halogen, ‒ CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², or wherein any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl or a 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy², or a pharmaceutically acceptable salt thereof. 16. The compound of claim 15, wherein each of R^21a, R^21b, and R^21c is independently selected from hydrogen, halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1- C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². 17. The compound of claim 15, wherein any adjacent two of R^21a, R^21b, and R^21c is covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl or a 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1- C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1- C4 alkyl), and Cy². 18. The compound of claim 15, wherein the compound has a structure represented by a formula: or a pharmaceutically acceptable salt thereof. 19. The compound of claim 1, wherein the compound has a structure represented by a formula: , wherein Z² is selected from ‒O‒, ‒S‒, and ‒N(R³²)‒; wherein R³² is selected from hydrogen and C1-C4 alkyl; wherein Z³ is selected from ‒N= and ‒C(R³³)‒; wherein R³³ is selected from hydrogen and C1-C4 alkyl; wherein each of R^22a and R^22b is independently selected from hydrogen, halogen, ‒CN, ‒ NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², or wherein R^22b is selected from hydrogen, halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², and wherein R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6- membered aryl or a 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH₂, ‒OH, ‒NO₂, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², or a pharmaceutically acceptable salt thereof. 20. The compound of claim 19, wherein each of R^22a and R^22b is independently selected from hydrogen, halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒ NR¹⁰CO₂(C1-C4 alkyl), and Cy². 21. The compound of claim 19, wherein R^22b is selected from hydrogen, halogen, ‒CN, ‒ NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO2(C1-C4 alkyl), and Cy², and wherein R^22a and R³³ are covalently bonded and, together with the intermediate atoms, comprise a 6-membered aryl or a 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, ‒CN, ‒NH2, ‒OH, ‒NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, ‒NR¹⁰C(O)(C1-C4 alkyl), ‒NR¹⁰CO₂(C1-C4 alkyl), and Cy². 22. The compound of claim 19, wherein the compound has a structure represented by a formula: or a pharmaceutically acceptable salt thereof. 23. The compound of claim 1, wherein the compound is selected from:

or a pharmaceutically acceptable salt thereof. 24. The compound of claim 1, wherein the compound is selected from: or a pharmaceutically acceptable salt thereof. 25. The compound of claim 1, wherein the compound is selected from: and or a pharmaceutically acceptable salt thereof. 26. A pharmaceutical composition comprising an effective amount of the compound of any one of claims 1 to 25 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. 27. A method of degrading a target protein in a cell, the method comprising contacting the cell with an effective amount of the compound of any one of claims 1 to 25 or a pharmaceutically acceptable salt thereof. 28. The method of claim 27, wherein the target protein is KDM4B or VCL. 29. The method of claim 27, wherein the cell is mammalian. 30. The method of claim 27, wherein the cell is human. 31. The method of claim 27, wherein the cell has been isolated from a mammal prior to the contacting step. 32. The method of claim 27, wherein the contacting is ex vivo. 33. The method of claim 27, wherein the contacting is in vitro. 34. The method of claim 27, wherein contacting is via administration to a mammal. 35. The method of claim 34, wherein the mammal has been diagnosed with a need for degrading the target protein prior to the administering step. 36. The method of claim 34, wherein the mammal has been diagnosed with a need for treatment of a cancer related to activity of the target protein prior to the administering step. 37. A method of degrading a target protein in a subject in need thereof, the method comprising administering to the subject an effective amount of the compound of any one of claims 1 to 25 or a pharmaceutically acceptable salt thereof. 38. The method of claim 37, wherein the subject is a mammal. 39. The method of claim 37, wherein the subject is a human. 40. The method of claim 37, wherein the subject has been diagnosed with a need for degrading the target protein prior to the administering step. 41. The method of claim 37, further comprising identifying a subject in need of degradation of the target protein. 42. A method of treating a cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of the compound of any one of claims 1 to 25 or a pharmaceutically acceptable salt thereof. 43. The method of claim 42, wherein the subject is a mammal. 44. The method of claim 42, wherein the subject is a human. 45. The method of claim 42, wherein the subject has been diagnosed with a need for treatment of the cancer prior to the administering step. 46. The method of claim 42, further comprising the step of identifying a subject in need of treatment of the cancer. 47. The method of claim 42, wherein the effective amount is a therapeutically effective amount. 48. The method of claim 42, wherein the effective amount is a prophylactically effective amount. 49. The method of claim 42, wherein the cancer is associated with activity of a protein selected from KDM4B and VCL. 50. The method of claim 42, wherein the cancer is selected from a sarcoma, a carcinoma, a hematological cancer, a solid tumor, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, non-small cell lung carcinoma, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, melanoma, glioma, leukemia, lymphoma, chronic myeloproliferative disorder, myelodysplastic syndrome, myeloproliferative neoplasm, and plasma cell neoplasm (myeloma). 51. The method of claim 42, wherein the cancer is leukemia. 52. A kit comprising the compound of any one of claims 1 to 25 or a pharmaceutically acceptable salt thereof, and one or more of: (a) an agent known to treat a cancer; (b) instructions for administering the compound in connection with treating a cancer; and (c) instructions for treating a cancer. 53. The kit of claim 52, wherein the agent is a chemotherapeutic agent. 54. The kit of claim 53, wherein the chemotherapeutic agent is selected from an alkylating agent, an antimetabolite agent, an antineoplastic antibiotic agent, a mitotic inhibitor agent, and an mTor inhibitor agent. 55. The kit of claim 54, wherein the antineoplastic antibiotic agent is selected from doxorubicin, mitoxantrone, bleomycin, daunorubicin, dactinomycin, epirubicin, idarubicin, plicamycin, mitomycin, pentostatin, and valrubicin, or a pharmaceutically acceptable salt thereof. 56. The kit of claim 54, wherein the antimetabolite agent is selected from gemcitabine, 5- fluorouracil, capecitabine, hydroxyurea, mercaptopurine, pemetrexed, fludarabine, nelarabine, cladribine, clofarabine, cytarabine, decitabine, pralatrexate, floxuridine, methotrexate, and thioguanine, or a pharmaceutically acceptable salt thereof. 57. The kit of claim 54, wherein the alkylating agent is selected from carboplatin, cisplatin, cyclophosphamide, chlorambucil, melphalan, carmustine, busulfan, lomustine, dacarbazine, oxaliplatin, ifosfamide, mechlorethamine, temozolomide, thiotepa, bendamustine, and streptozocin, or a pharmaceutically acceptable salt thereof. 58. The kit of claim 54, wherein the mitotic inhibitor agent is selected from irinotecan, topotecan, rubitecan, cabazitaxel, docetaxel, paclitaxel, etopside, vincristine, ixabepilone, vinorelbine, vinblastine, and teniposide, or a pharmaceutically acceptable salt thereof. 59. The kit of claim 54, wherein the mTor inhibitor agent is selected from everolimus, siroliumus, and temsirolimus, or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof. 60. The kit of any one of claims 52 to 59, wherein the compound and the agent are co- packaged.