Cross-Reference to Related Applications

[0001] This application claims priority to U.S. Provisional Application No. 63/303,368, filed on January 26, 2022, and U.S. Provisional Application No. 63/435,212, filed on December 23, 2022, which are incorporated by reference herein in their entireties and for all purposes.

Field

[0002] Provided herein are compounds, and compositions and methods thereof. In some embodiments, provided are compounds for inhibiting protein arginine methyltransferase 5 (PRMT5). In some embodiments, provided are methods for treatment of diseases or disorders, such as cancer.

Background

[0003] Protein arginine methyltransferase 5 (PRMT5) is a type II arginine methyltransferase that regulates essential cellular functions, including the regulation of cell cycle progression, apoptosis and the DNA-damage response (Koh, C. et al., CurrMol Bio Rep 2015; Wu et al., Nat Rev Drug Discovery 2021). MTAP is a critical enzyme in the methionine salvage pathway, a six-step process that recycles methionine from the product of polyamine synthesis, methylthioadenosine (MTA). Loss of MTAP causes the accumulation of its substrate, MTA, which has been described to function as a SAM-competitive PRMT5 inhibitor (Kruykov et al., 2016; Marjon et al., 2016 and Markarov et al., 2016). Data from genome-wide genetic perturbation screens using shRNA suggests a selective requirement for PRMT5 activity particularly in MTAP-deleted cancer cell lines (Kruykov et al., 2016; Marjon et al., 2016 and Markarov et al., 2016). It is proposed that the accumulation of MTA caused by MTAP-deletion in these cell lines partially inhibits PRMT5, rendering those cells selectively sensitive to additional PRMT5 inhibition.

[0004] A PRMT5 inhibitor that leverages the accumulation of MTA by binding in an MTA- uncompetitive, non-competitive or mixed mode manner or in a MTA-cooperative binding manner may demonstrate selectivity for MTAP -deleted tumor cells. Some PRMT5 inhibitors are currently being explored for therapeutic uses (e.g., for treating cancer), however there are currently no such PRMT5 therapies approved by the United States Food and Drug Administration that demonstrate selectivity for MTAP-deleted cancer cell lines. [0005] Accordingly, there is a need for PRMT5 inhibitors for treating diseases, such as cancers. Summary [0006] In one embodiment, provided is a compound of Formula (I) or Formula (A): or a pharmaceutically acceptable salt thereof, wherein: Ring A is an optionally substituted fused bicyclic 8-10 membered heteroaryl ring system containing at least one nitrogen atom, wherein the 8-10 membered refers to the total number of atoms in the fused system; R ^B is an optionally substituted C ₁ -C ₆ alkyl; Ring B is selected from the group consisting of –C ₃ –C ₁₀ carbocyclyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, wherein each carbocyclyl, heterocyclyl, aryl and heteroaryl is optionally substituted at any available position; each R ¹ is independently absent or selected from the group consisting of H, –D, halo, –CN, – C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, 5-6-membered monocyclic heteroaryl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a1 , –N(R ^a1 ) ₂ , –C(=O)R ^a1 , –C(=O)OR ^a1 , –NR ^a1 C(=O)R ^a1 , – NR ^a1 C(=O)OR ^a1 , –C(=O)N(R ^a1 ) ₂ , –OC(=O)N(R ^a1 ) ₂ , –S(=O)R ^a1 , –S(=O) ₂ R ^a1 , –SR ^a1 , – S(=O)(=NR ^a1 )R ^a1 , –NR ^a1 S(=O) ₂ R ^a1 and –S(=O) ₂ N(R ^a1 ) ₂ ; each R ² is independently selected from the group consisting of –D, =O, halo, –CN, – C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a2 , –N(R ^a2 ) ₂ , –C(=O)R ^a2 , –C(=O)OR ^a2 , –NR ^a2 C(=O)R ^a2 , –NR ^a2 C(=O)OR ^a2 , –CH ₂ C(=O)N(R ^a2 ) ₂ – C(=O)N(R ^a2 ) ₂ , –OC(=O)N(R ^a2 ) ₂ , –CH ₂ C(=O)N(R ^a2 ) ₂ , –S(=O)R ^a2 , –S(=O) ₂ R ^a2 , –SR ^a2 , – S(=O)(=NR ^a2 )R ^a2 , –NR ^a2 S(=O) ₂ R ^a2 and –S(=O) ₂ N(R ^a2 ) ₂ or two instances of R ² together with the atom or atoms to which they are attached can be taken together to form a 3-10 membered cycloalkyl or heterocyclyl ring (e.g., a ring that together with the piperidine ring of Formula (I) or Formula (A) can form a bridged, fused or spiro bicyclic heterocyclic ring); each R ^a1 and R ^a2 is independently selected from the group consisting of H, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, C6-C ₁₀ aryl, 5-10 membered heteroaryl, arylalkyl and heteroarylalkyl wherein each alkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is independently selected from the group consisting of =O, halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, – OR ^b , –N(R ^b ) ₂ , –C(=O)R ^b , –C(=O)OR ^b , –NR ^b C(=O)R ^b , –NR ^b C(=O)OR ^b , –C(=O)N(R ^b ) ₂ , – OC(=O)N(R ^b ) ₂ , –S(=O)R ^b , –S(=O) ₂ R ^b , –SR ^b , –S(=O)(=NR ^b )R ^b , –NR ^b S(=O) ₂ R ^b and – S(=O) ₂ N(R ^b ) ₂ , wherein each R ^b is independently selected from the group consisting of H, – C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu)), and C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl); and n is 0, 1, 2 or 3; provided that: (i) when the compound is of Formula (A), Ring A is a 3-pyridine fused with a 5-membered heteroaryl via 2 carbon atoms; and (ii) the compound is not one of compounds a. to d. or a pharmaceutically acceptable salt thereof: a. N-(8-fluoroquinolin-3-yl)-2-oxo-2-(2-phenylpiperidin-l-yl)ac etamide b. 2-(2-(lH-pyrazol-4-yl)piperidin-l-yl)-N-(lH-indol-4-yl)-2-ox oacetamide c. 2-(2-(4-bromophenyl)piperidin- 1 -yl)-2-oxo-N-(pyrazolo [ 1 ,5 -a]pyrimidin-3 - yl)acetamide d. 2-(2-(lH-pyrazol-4-yl)piperidin-l-yl)-N-(lH-indazol-5-yl)-2- oxoacetamide

[0007] In one embodiment, provided is a pharmaceutical composition comprising a compound of Formula (A) or Formula (I) to (III7a), or a pharmaceutically acceptable salt thereof, as defined in any of the embodiments described herein and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition further comprises a second therapeutic agent.

[0008] In one embodiment, provided is a method of treating an MTAP -deficient and/or an MTA-accumulating disease in a subject in need thereof by administering to the subject an effective amount (e.g., a therapeutically effective amount) of compound of Formula (A) and Formula (I) to (III7a), or a pharmaceutically acceptable salt thereof, as defined in any of the embodiments described herein or a pharmaceutically acceptable composition thereof. In some embodiments, the compound or composition is administered in combination with a second therapeutic agent. [0009] In one embodiment, provided is a method of treating a cancer in a subject in need thereof comprising the steps of: a) assessing the level of MTAP and/or MTA in a test sample obtained from said subject, wherein the MTA level can be assessed directly (e.g., by ELISA or LC-MS/MS) or indirectly (e.g., by SDMA-modified protein ELISA or IHC, or by RNA splicing); b) comparing the test sample with a reference, wherein MTAP deficiency and/or MTA accumulation in said test sample compared to the reference indicates the cancer in said subject will respond to therapeutic treatment with a PRMT5 inhibitor; and c) administering an effective amount (e.g., a therapeutically effective amount) of a compound of Formula (A) or Formula (I) to (III7a) as defined herein or a pharmaceutical composition thereof to the subject identified in step b). [0010] In an embodiment, provided is a use of a compound of Formula (A) or Formula (I) to (III7a), or a pharmaceutically acceptable salt thereof, as defined in any of the embodiments described herein, or of a pharmaceutically acceptable composition as described herein for treating an MTAP-deficient and/or an MTA-accumulating disease in a subject in need thereof. In an embodiment, the compound or composition is configured to be administered in combination with a second therapeutic agent. [0011] In an embodiment, provided is a compound of Formula (A) or Formula (I) to (III7a), or a pharmaceutically acceptable salt thereof, as defined in any of the embodiments described herein, or a pharmaceutically acceptable composition as described herein for treating an MTAP-deficient and/or an MTA-accumulating disease in a subject in need thereof. In an embodiment, the compound or composition is configured to be administered in combination with a second therapeutic agent. [0012] In an embodiment, provided is a use of a compound of compound of Formula (A) or Formula (I) to (III7a), or a pharmaceutically acceptable salt thereof, as defined in any of the embodiments described herein, or of a pharmaceutically acceptable composition as described herein in the manufacturing of a medicament for treating an MTAP-deficient and/or an MTA- accumulating disease in a subject in need thereof. In an embodiment, the medicament is configured to be administered in combination with a second therapeutic agent. Detailed Description [0013] The disclosure herein sets forth exemplary methods, parameters and the like. It should be recognized, however, that such description is not intended as a limitation on the scope of the present disclosure but is instead provided as a description of exemplary embodiments. [0014] As generally described herein, provided are compounds (e.g., compounds of Formula (A) and Formula (I) to (III7a) or compounds of Table 1, or pharmaceutically acceptable salts thereof) that are MTA-uncompetitive PRMT5 inhibitors useful for treating proliferating disorders (e.g., cancers) associated with MTAP deficiencies and/or MTA accumulation. [0015] In some embodiments, provided are compounds (e.g., compounds of Formula (A) and Formula (I) to (III7a) or compounds of Table 1, or pharmaceutically acceptable salts thereof) that are MTA-uncompetitive, non-competitive or mixed mode PRMT5 inhibitor or an MTA cooperative binding agent useful for treating proliferating disorders (e.g., cancers) associated with MTAP deficiencies and/or MTA accumulation. Definitions [0016] As used in the present disclosure, the following words and phrases are generally intended to have the meanings as set forth below unless expressly indicated otherwise or the context in which they are used indicates otherwise. MTAP [0017] “MTAP” as used herein refers to methylthioadenosine phosphorylase, an enzyme in the methionine salvage pathway, also known as S-methyl-5'-thioadenosine phosphorylase; also known as BDMF; DMSFH; DMSMFH; LGMBF; MSAP; and c86fus. External IDs: OMIM: 156540 MGI: 1914152 HomoloGene:1838 chEMBL: 4941 GeneCards: MTAP Gene; Entrez 4507; RefSeq (mRNA): NM_002451; location: Chr 9: 21.8–21.93 Mb. By “wild-type” MTAP is meant that encoded by NM_002451 or having the same amino acid sequence (NP_002442). (Schmid et al. Oncogene 2000, 19, pp 5747-54). As used herein, the term “MTAP-deficient”,“MTAP-deficiency”,“MTAP-null” and the like refer to cells (including, but not limited to, cancer cells, cell lines, tissues, tissue types, tumors, etc.) that have a significant reduction in post-translational modification, production, expression, level, stability and/or activity of MTAP relative to that in a control, e.g., reference or normal or non-cancerous cells. The reduction can be at least about 20%, 30%, 40%, 50%, 60%, 70%, 80% or 90%. In some embodiments, the reduction is at least 20%. In some embodiments, the reduction is at least 50%. The terms “MTAP-deficient and/or MTA accumulating”, “MTAP-deficient and/or MTA-accumulating”, MTAP deficient and/or MTA upregulated” and the like, regarding a cell or cells, etc., indicate that the cell or cells, etc., either are deficient in MTAP and/or overproduce or accumulate MTA. MTAP-deficient cells include those wherein the MTAP gene has been mutated, deleted, or transcriptionally silenced. As a non-limiting example, MTAP-deficient cells can have a homozygous deletion. MTAP knockdown is not lethal. In some embodiments, the MTAP-deficient cells are also CDKN2A-deficient. The MTAP deficiency can be detected using any reagent or technique known in the art, for example: immunohistochemistry utilizing an antibody to MTAP, and/or genomic sequencing, and/or nucleic acid hybridization and/or amplification utilizing at least one probe or primer comprising a sequence of at least 12 contiguous nucleotides (nt) of the sequence of MTAP, wherein the primer is no longer than about 30 nt. [0018] An “MTAP-deficiency-related” or “MTAP-deficiency” or “MTAP deficient” disease (for example, a proliferating disease, e.g., a cancer) or a disease (for example, a proliferating disease, e.g., a cancer)“associated with MTAP deficiency” or a disease (for example, a proliferating disease, e.g., a cancer) “characterized by MTAP deficiency” and the like refer to an ailment (for example, a proliferating disease, e.g., a cancer) wherein a significant number of cells are MTAP-deficient. For example, in a MTAP-deficiency-related disease, one or more disease cells can have a significantly reduced post-translational modification, production, expression, level, stability and/or activity of MTAP. Examples of MTAP-deficiency-related diseases include, but are not limited to, cancers, including but not limited to: glioblastoma, malignant peripheral nerve sheath tumors (MPNST), esophageal cancer (e.g., esophageal squamous cell carcinoma or esophageal adenocarcinoma), bladder cancer (e.g., bladder urothelial carcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma), mesothelioma, melanoma, non-small cell lung cancer (NSCLC; e.g., lung squamous or lung adenocarcinoma), astrocytoma, undifferentiated pleiomorphic sarcoma, diffuse large B-cell lymphoma (DLBCL), leukemia, head and neck cancer, stomach adenocarcinoma, myxofibrosarcoma, cholangiosarcoma, cancer of the brain, stomach, kidney, breast, endometrium, urinary tract, liver, soft tissue, pleura and large intestine or sarcoma (See FIG.1). In a patient afflicted with a MTAP-deficiency-related disease, it is possible that some disease cells (e.g., cancer cells) can be MTAP-deficient while others are not. Similarly, some disease cells may be MTA-accumulating while others are not. Thus, the present disclosure encompasses methods of treatment involving diseases of these tissues, or any other tissues, wherein the proliferation of MTAP-deficient and/or MTA- accumulating cells can be inhibited by administration of a PRMT5 inhibitor. Some cancer cells which are MTAP-deficient are also deficient in CDKN2A; the post- translational modification, production, expression, level, stability and/or activity of the CDKN2A gene or its product are decreased in these cells. The genes for MTAP and CDKN2A are in close proximity on chromosome 9p21; MTAP is located approximately 100 kb telomeric to CDKN2A. Many cancer cell types harbor CDKN2A/MTAP loss (loss of both genes). Thus, in some embodiments, a MTAP-deficient cell is also deficient in CDKN2A. MTA and MTA accumulation [0019] By “MTA” is meant the PRMT5 inhibitor also known as methyl-thioadenosine, S- methyl-5’-thioadenosine, [5'deoxy-5'-(methylthio)-fl-D-ribofuranosyl] adenine, 5'-methyl- thioadenosine, 5'-deoxy, 5'-methyl thioadenosine, and the like. MTA selectively inhibits PRMT5 methyltransferase activity. MTA is the sole known catabolic substrate for MTAP. The terms “MTA accumulating”, “MTA overproducing”, “MTA upregulated” and the like refer to cells (including, but not limited to, cancer cells, cell lines, tissues, tissue types, tumors, etc.) that have a significantly increased production, level and/or stability of MTA. MTA-accumulating cells include those wherein the cells comprise at least about 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or greater than 100%, higher production, level and/or stability of MTA than that in normal or non-cancerous cells. In some embodiments, MTA-accumulating cells include those wherein the cells comprise at least 20% higher production, level and/or stability of MTA than that in normal or non-cancerous cells. In some embodiments, MTA-accumulating cells include those wherein the cells comprise at least 50% higher production, level and/or stability of MTA than that in normal or non- cancerous cells. Determination of MTA accumulation in test samples (e.g., cells such as cancer cells being tested for MTA accumulation) and reference samples, and other cells, tissues, samples, etc., can be performed using any method known in the art. Such methods for detecting MTA include, as a non-limiting example, liquid chromatography–electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS), as described in Stevens et al. J. Chromatogr. A. 2010, 1217, pp 3282-3288; and Kirovski et al. Am. J. Pathol. 2011, 178, pp 1145-1152; and references cited therein. Loss of MTAP is associated with accumulation of MTA (Williams-Ashman et al. Biochem. Pharm. 1982, 31, pp 277-288; and Limm et al. Eur. J. Cancer. 2013, 49, Issue 6. [0020] An “MTA-accumulation-related”, “MTA-accumulation”, “MTA-accumulating”, “MTA overproducing”, “MTA upregulated” disease (for example, a proliferating disease, e.g., a cancer) or a disease (for example, a proliferating disease, e.g., a cancer) “associated with MTA accumulation” or a disease (for example, a proliferating disease, e.g., a cancer) “characterized by MTA accumulation” and the like refer to an ailment (for example, a proliferating disease, e.g., a cancer) wherein a significant number of cells are MTA accumulating. Examples of MTA-accumulating diseases include, but are not limited to, cancers, including but not limited to: glioblastoma, malignant peripheral nerve sheath tumors (MPNST), esophageal cancer (e.g., esophageal squamous cell carcinoma or esophageal adenocarcinoma), bladder cancer (e.g., bladder urothelial carcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma), mesothelioma, melanoma, non-small cell lung cancer (NSCLC; e.g., lung squamous or lung adenocarcinoma), astrocytoma, undifferentiated pleiomorphic sarcoma, diffuse large B-cell lymphoma (DLBCL), leukemia, head and neck cancer, stomach adenocarcinoma, myxofibrosarcoma, cholangiosarcoma, cancer of the brain, stomach, kidney, breast, endometrium, urinary tract, liver, soft tissue, pleura and large intestine or sarcoma (See FIG.1). In a patient afflicted with a MTAP-deficiency-related disease, it is possible that some disease cells (e.g., cancer cells) can be MTAP-deficient while others are not. In a patient having or having been diagnosed with an MTA-accumulating disease, some cells may be MTA-accumulating while others are not. [0021] An increase in therapeutic window between normal cells and MTAP-deleted/MTA accumulating cells could be achieved by using an inhibitor that binds PRMT5 uncompetitively with MTA. As used herein, “uncompetitive binding” and “uncompetitive inhibition” and “cooperative binding” and “cooperative inhibition” (e.g., MTA-uncompetitive binding, MTA-uncompetitive inhibition, MTA-cooperative binding, MTA-cooperative inhibition) refers to binding of an inhibitor to a protein (e.g., PRMT5) that is increased in the presence of a co-factor (e.g., MTA) over the binding of the same inhibitor in the absence of the co-factor. The PRMT5 inhibitors known in the art are generally either SAM (S- adenosylmethionine) uncompetitive or SAM competitive. As the concentration of SAM in wild-type and MTAP-null cells is similar, these inhibitors are expected to bind with similar potency to both cell types. By contrast, an MTA-cooperative (and either SAM competitive or showing enhanced cooperativity with MTA relative to SAM) inhibitor would bind with apparent greater potency in the presence of high concentrations of MTA and would therefore result in preferential inhibition of PRMT5 in MTA-accumulating cells relative to normal cells. [0022] As described further herein, a cancer cell, a cancer type, or a subject with cancer, is “PRMT5 inhibitor sensitive,” sensitive to treatment with PRMT5 inhibitors,” sensitive to PRMT5 therapeutic inhibition,” or described in similar terms if it is amenable to treatment with a PRMT5 inhibitor, e.g., due to its MTAP deficiency and/or MTA accumulation character. PRMT5 [0023] "PRMT5" as used herein is the gene or protein Protein Arginine Methyltransferase 5, also known as HRMT1L5; IBP72; JBP1; SKB1; or SKB1Hs External IDs: OMIM: 604045, MGI: 1351645, HomoloGene: 4454, ChEMBL: 1795116, GeneCards: PRMT5 Gene; EC number 2.1.1.125. Ensembl ENSG00000100462; UniProt O14744; Entrez Gene ID: 10419; RefSeq (mRNA): NM_001039619. The mouse homolog is NM_013768. Methyltransferases such as PRMT5 catalyze the transfer of one to three methyl groups from the co-factor S-adenosylmethionine (also known as SAM or AdoMet) to lysine or arginine residues of histone proteins. Arginine methylation is carried out by 9 different protein arginine methyltransferases (PRMT) in humans. Three types of methylarginine species exist: (1) Monomethylarginine (MMA); (2) Asymmetric dimethyl arginine (ADMA), which is produced by Type I methyl transferases (PRMT1, PRMT2, PRMT3, CARM1, PRMT6 and PRMT8); and (3) Symmetrical dimethylarginine (SDMA), which is produced by Type II methyl transferases (PRMT5 and PRMT7). PRMT1 and PRMT5 are the major asymmetric and symmetric arginine methyltransferases, respectively. PRMT5 promotes symmetric dimethylation on histones at H3R8 and H4R3 (H4R3me2). Symmetric methylation of H4R3 is associated with transcriptional repression and can act as a binding site for DNMT3A. Loss of PRMT5 results in reduced DNMT3A binding and gene activation. Tumor suppressor gene ST7 and chemokines RNATES, IP10, CXCL11 are targeted and silenced by PRMT5. WO 2011/079236. [0024] Additional substrates include E2F1, p53, EGFR and CRAF. PRMT5 is part of a multi-protein complex comprising the co-regulatory factor WDR77 (also known as MEP50, a CDK4 substrate) during G1/S transition. Phosphorylation increases PRMT5/WDR77 activity. WDR77 is the non-catalytic component of the complex and mediates interactions with binding partners and substrates. PRMT5 can also interact with pICIn or RioKl adaptor proteins in a mutually exclusive fashion to modulate complex composition and substrate specificity.

[0025] PRMT5 has either a positive or negative effect on its substrates by arginine methylation when interacting with a number of complexes and is involved in a variety of cellular processes, including RNA processing, signal transduction, transcriptional regulation, and germ cell development. PRMT5 is a major pro-survival factor regulating eIF4E expression and p53 translation. PRMT5 triggers p53-dependent apoptosis and sensitized various cancer cells to Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) without affecting TRAIL resistance in non-transformed cells.

[0026] The term “PRMT5 inhibitor” refers to any compound capable of inhibiting the production, level, activity, expression or presence of PRMT5. These include, as non-limiting examples, any compound inhibiting the transcription of the gene, the maturation of RNA, the translation of mRNA, the posttranslational modification of the protein, the enzymatic activity of the protein, the interaction of same with a substrate, etc. The term also refers to any agent that inhibits the cellular function of the PRMT5 protein, either by ATP -competitive inhibition of the active site, allosteric modulation of the protein structure, disruption of protein-protein interactions, or by inhibiting the transcription, translation, post-translational modification, or stability of PRMT5 protein.

[0027] In some embodiments, a PRMT5 inhibitor competes with another compound, protein or other molecule which interacts with PRMT5 and is necessary for PRMT5 function. As a non-limiting example, a PRMT5 inhibitor can compete with the co-factor S- adenosylmethionine (also known as SAM or AdoMet).

In some embodiments, the PRMT5 inhibitor is uncompetitive with MTA. In some embodiments, the PRMT5 inhibitor is uncompetitive with MTA and competitive with SAM. In some embodiments, the PRMT5 inhibitor is uncompetitive with MTA and uncompetitive with SAM but binds with a higher degree of potency for the MTA complex relative to the SAM complex.

Chemical Definitions

[0028] Definitions of specific functional groups and chemical terms are described in more detail below. The chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75 ^th Ed., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Thomas Sorrell, Organic Chemistry, University Science Books, Sausalito, 1999; Smith and March, March’s Advanced Organic Chemistry, 5 ^th Edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; and Carruthers, Some Modern Methods of Organic Synthesis, 3 ^rd Edition, Cambridge University Press, Cambridge, 1987. [0029] Compounds described herein can comprise one or more asymmetric centers, and thus can exist in various isomeric forms, e.g., enantiomers and/or diastereomers. For example, the compounds described herein can be in the form of an individual enantiomer, diastereomer or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high- pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric syntheses. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725 (1977); Eliel, Stereochemistry of Carbon Compounds (McGraw– Hill, NY, 1962); and Wilen, Tables of Resolving Agents and Optical Resolutions p. 268 (E.L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972). Additionally encompassed are compounds described herein as individual isomers substantially free of other isomers, and alternatively, as mixtures of various isomers. [0030] The “enantiomeric excess” (“e.e.”) or “% enantiomeric excess” (“%e.e.”) of a composition as used herein refers to an excess of one enantiomer relative to the other enantiomer present in the composition. For example, a composition can contain 90% of one enantiomer, e.g., the S enantiomer, and 10% of the other enantiomer, i.e., the R enantiomer. e.e. = (90-10)/100 = 80%. [0031] Thus, a composition containing 90% of one enantiomer and 10% of the other enantiomer is said to have an enantiomeric excess of 80%. [0032] The “diastereomeric excess” (“d.e.”) or “% diastereomeric excess” (“%d.e.”) of a composition as used herein refers to an excess of one diastereomer relative to one or more different diastereomers present in the composition. For example, a composition can contain 90% of one diastereomer, and 10% of one or more different diastereomers. d.e. = (90-10)/100 = 80%. [0033] Thus, a composition containing 90% of one diastereomers and 10% of one or more different diastereomers is said to have a diastereomeric excess of 80%. In an alternative embodiment, compounds described herein may also comprise one or more isotopic substitutions. For example, hydrogen may be ² H (D or deuterium) or ³ H (T or tritium); carbon may be, for example, ¹³ C or ¹⁴ C; oxygen may be, for example, ¹⁸ O; nitrogen may be, for example, ¹⁵ N, and the like. In other embodiments, a particular isotope (e.g., ³ H, ¹³ C, ¹⁴ C, ¹⁸ O, or ¹⁵ N) can represent at least 1%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or at least 99.9% of the total isotopic abundance of an element that occupies a specific site of the compound. [0034] In a formula, is a single bond where the stereochemistry of the moieties immediately attached thereto is not specified. When a range of values is listed, it is intended to encompass each value and sub–range within the range. For example, “C _1–6 alkyl” is intended to encompass, C ₁ , C ₂ , C ₃ , C ₄ , C ₅ , C ₆ , C _1–6 , C _1–5 , C _1–4 , C _1–3 , C _1–2 , C _2–6 , C _2–5 , C _2–4 , C _2–3 , C _3–6 , C _3–5 , C _3–4 , C _4–6 , C _4–5 , and C _5–6 alkyl. It should also be understood that when described herein any of the moieties defined forth below may be substituted with a variety of substituents, and that the respective definitions are intended to include such substituted moieties within their scope as set out below. Unless otherwise stated, the term “substituted” is to be defined as set out below. It should be further understood that the terms “groups” and “radicals” can be considered interchangeable when used herein. The articles “a” and “an” may be used herein to refer to one or to more than one (i.e. at least one) of the grammatical objects of the article. By way of example “an analogue” means one analogue or more than one analogue. [0035] The term “unsaturated bond” refers to a double or triple bond. [0036] The term “unsaturated” or “partially unsaturated” refers to a moiety that includes at least one double or triple bond. [0037] The term “saturated” refers to a moiety that does not contain a double or triple bond, i.e., the moiety only contains single bonds. Affixing the suffix “-ene” to a group indicates the group is a divalent moiety, e.g., alkylene is the divalent moiety of alkyl, alkenylene is the divalent moiety of alkenyl, alkynylene is the divalent moiety of alkynyl, heteroalkylene is the divalent moiety of heteroalkyl, heteroalkenylene is the divalent moiety of heteroalkenyl, heteroalkynylene is the divalent moiety of heteroalkynyl, carbocyclylene is the divalent moiety of carbocyclyl, heterocyclylene is the divalent moiety of heterocyclyl, arylene is the divalent moiety of aryl, and heteroarylene is the divalent moiety of heteroaryl. [0038] The term “azido” refers to the radical –N ₃ . “Aliphatic” refers to an alkyl, alkenyl, alkynyl, or carbocyclyl group, as defined herein. “Cycloalkylalkyl” refers to an alkyl radical in which the alkyl group is substituted with a cycloalkyl group. Typical cycloalkylalkyl groups include, but are not limited to, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclooctylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, cycloheptylethyl, and cyclooctylethyl, and the like. [0039] “Heterocyclylalkyl” refers to an alkyl radical in which the alkyl group is substituted with a heterocyclyl group (e.g., a 3-10 membered heterocyclyl containing 1, 2 or 3 heteroatoms selected from N, O, S and oxidized forms thereof). In some embodiments, a heterocyclylalkyl is a C _1-2 alkyl-heterocyclyl (e.g., –CH ₂ -heterocyclyl, –CH ₂ CH ₂ - heterocyclyl, –CH(CH ₃ )-heterocyclyl). In some embodiments, a heterocyclylalkyl is a –CH ₂ - heterocyclyl. . Typical heterocyclylalkyl groups include, but are not limited to, tetrahydrofuranylmethyl, tetrahydropyranylmethyl, pyrrolidinylmethyl, piperidinylmethyl, piperazinylmethyl, morpholinylmethyl, pyrrolidinylethyl, piperidinylethyl, piperazinylethyl, morpholinylethyl, and the like. “Aralkyl” or “arylalkyl” is a subset of alkyl and aryl, as defined herein, and refers to an alkyl group substituted by an aryl group (e.g., a C ₆ -C ₁₀ aryl group). In some embodiments, arylalkyl is a C _1-2 alkyl-aryl (e.g., –CH ₂ -aryl, –CH ₂ CH ₂ -aryl, –CH(CH ₃ )-aryl). In some embodiments, arylalkyl is a –CH ₂ -aryl (e.g., –CH ₂ -phenyl, –CH ₂ -naphthyl). “Alkyl” refers to a radical of a straight–chain or branched saturated hydrocarbon group having from 1 to 20 carbon atoms (“C _1–20 alkyl” or “C ₁ -C ₂₀ alkyl”). In some embodiments, an alkyl group has 1 to 12 carbon atoms (“C _1–12 alkyl”). In some embodiments, an alkyl group has 1 to 10 carbon atoms (“C _1–10 alkyl”). In some embodiments, an alkyl group has 1 to 9 carbon atoms (“C _1–9 alkyl”). In some embodiments, an alkyl group has 1 to 8 carbon atoms (“C _1–8 alkyl”). In some embodiments, an alkyl group has 1 to 7 carbon atoms (“C _1–7 alkyl”). In some embodiments, an alkyl group has 1 to 6 carbon atoms (“C _1–6 alkyl”, also referred to herein as “lower alkyl”). In some embodiments, an alkyl group has 1 to 5 carbon atoms (“C _1–5 alkyl”). In some embodiments, an alkyl group has 1 to 4 carbon atoms (“C _1–4 alkyl”). In some embodiments, an alkyl group has 1 to 3 carbon atoms (“C _1–3 alkyl”). In some embodiments, an alkyl group has 1 to 2 carbon atoms (“C _1–2 alkyl”). In some embodiments, an alkyl group has 1 carbon atom (“C ₁ alkyl”). In some embodiments, an alkyl group has 2 to 6 carbon atoms (“C _2–6 alkyl”). Examples of C _1–6 alkyl groups include methyl (C ₁ ), ethyl (C ₂ ), n–propyl (C ₃ ), isopropyl (C ₃ ), n–butyl (C ₄ ), tert–butyl (C ₄ ), sec–butyl (C ₄ ), iso–butyl (C ₄ ), n–pentyl (C ₅ ), 3–pentanyl (C ₅ ), amyl (C ₅ ), neopentyl (C ₅ ), 3–methyl–2– butanyl (C ₅ ), tertiary amyl (C ₅ ), and n–hexyl (C ₆ ). Additional examples of alkyl groups include n–heptyl (C ₇ ), n–octyl (C ₈ ) and the like. Unless otherwise specified, each instance of an alkyl group is independently optionally substituted, i.e., unsubstituted (an “unsubstituted alkyl”) or substituted (a “substituted alkyl”) with one or more substituents; e.g., for instance from 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. In certain embodiments, the alkyl group is unsubstituted C _1–10 alkyl (e.g., –CH ₃ ). In certain embodiments, the alkyl group is substituted C _1–10 alkyl. Common alkyl abbreviations include Me (–CH ₃ ), Et (–CH ₂ CH ₃ ), ⁱ Pr (–CH(CH ₃ ) ₂ ), ⁿ Pr (–CH ₂ CH ₂ CH ₃ ), ⁿ Bu (–CH ₂ CH ₂ CH ₂ CH ₃ ), or ⁱ Bu (–CH ₂ CH(CH ₃ ) ₂ ). [0040] “Alkylene” refers to an alkyl group wherein two hydrogens are removed to provide a divalent radical, and which may be substituted or unsubstituted. Unsubstituted alkylene groups include, but are not limited to, methylene (–CH ₂ -), ethylene (–CH ₂ CH ₂ -), propylene (– CH ₂ CH ₂ CH ₂ -), butylene (–CH ₂ CH ₂ CH ₂ CH ₂ -), pentylene (–CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ -), hexylene (–CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ -), and the like. Exemplary substituted alkylene groups, e.g., substituted with one or more alkyl (methyl) groups, include but are not limited to, substituted methylene (–CH(CH ₃ )-, (–C(CH ₃ ) ₂ -), substituted ethylene (–CH(CH ₃ )CH ₂ -,–CH ₂ CH(CH ₃ )-, –C(CH ₃ ) ₂ CH ₂ -,–CH ₂ C(CH ₃ ) ₂ -), substituted propylene (–CH(CH ₃ )CH ₂ CH ₂ -, – CH ₂ CH(CH ₃ )CH ₂ -, –CH ₂ CH ₂ CH(CH ₃ )-, –C(CH ₃ ) ₂ CH ₂ CH ₂ -, –CH ₂ C(CH ₃ ) ₂ CH ₂ -, – CH ₂ CH ₂ C(CH ₃ ) ₂ -), and the like. When a range or number of carbons is provided for a particular alkylene group, it is understood that the range or number refers to the range or number of carbons in the linear carbon divalent chain. Alkylene groups may be substituted or unsubstituted with one or more substituents as described herein. [0041] “Alkenyl” refers to a radical of a straight–chain or branched hydrocarbon group having from 2 to 20 carbon atoms, one or more carbon–carbon double bonds (e.g., 1, 2, 3, or 4 carbon–carbon double bonds), and optionally one or more carbon–carbon triple bonds (e.g., 1, 2, 3, or 4 carbon–carbon triple bonds) (“C _2–20 alkenyl”). In certain embodiments, alkenyl does not contain any triple bonds. In some embodiments, an alkenyl group has 2 to 10 carbon atoms (“C _2–10 alkenyl”). In some embodiments, an alkenyl group has 2 to 9 carbon atoms (“C _2–9 alkenyl”). In some embodiments, an alkenyl group has 2 to 8 carbon atoms (“C _2–8 alkenyl”). In some embodiments, an alkenyl group has 2 to 7 carbon atoms (“C _2–7 alkenyl”). In some embodiments, an alkenyl group has 2 to 6 carbon atoms (“C _2–6 alkenyl”). In some embodiments, an alkenyl group has 2 to 5 carbon atoms (“C _2–5 alkenyl”). In some embodiments, an alkenyl group has 2 to 4 carbon atoms (“C _2–4 alkenyl”). In some embodiments, an alkenyl group has 2 to 3 carbon atoms (“C _2–3 alkenyl”). In some embodiments, an alkenyl group has 2 carbon atoms (“C ₂ alkenyl”). The one or more carbon– carbon double bonds can be internal (such as in 2–butenyl) or terminal (such as in 1–butenyl). Examples of C _2–4 alkenyl groups include ethenyl (C ₂ ), 1–propenyl (C ₃ ), 2–propenyl (C ₃ ), 1– butenyl (C ₄ ), 2–butenyl (C ₄ ), butadienyl (C ₄ ), and the like. Examples of C _2–6 alkenyl groups include the aforementioned C _2–4 alkenyl groups as well as pentenyl (C ₅ ), pentadienyl (C ₅ ), hexenyl (C ₆ ), and the like. Additional examples of alkenyl include heptenyl (C ₇ ), octenyl (C ₈ ), octatrienyl (C ₈ ), and the like. Unless otherwise specified, each instance of an alkenyl group is independently optionally substituted, i.e., unsubstituted (an “unsubstituted alkenyl”) or substituted (a “substituted alkenyl”) with one or more substituents e.g., for instance from 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. In certain embodiments, the alkenyl group is unsubstituted C _2–10 alkenyl. In certain embodiments, the alkenyl group is substituted C _2–10 alkenyl. [0042] “Alkynyl” refers to a radical of a straight–chain or branched hydrocarbon group having from 2 to 20 carbon atoms, one or more carbon–carbon triple bonds (e.g., 1, 2, 3, or 4 carbon–carbon triple bonds), and optionally one or more carbon–carbon double bonds (e.g., 1, 2, 3, or 4 carbon–carbon double bonds) (“C _2–20 alkynyl”). In certain embodiments, alkynyl does not contain any double bonds. In some embodiments, an alkynyl group has 2 to 10 carbon atoms (“C _2–10 alkynyl”). In some embodiments, an alkynyl group has 2 to 9 carbon atoms (“C _2–9 alkynyl”). In some embodiments, an alkynyl group has 2 to 8 carbon atoms (“C _2–8 alkynyl”). In some embodiments, an alkynyl group has 2 to 7 carbon atoms (“C _2–7 alkynyl”). In some embodiments, an alkynyl group has 2 to 6 carbon atoms (“C _2–6 alkynyl”). In some embodiments, an alkynyl group has 2 to 5 carbon atoms (“C _2–5 alkynyl”). In some embodiments, an alkynyl group has 2 to 4 carbon atoms (“C _2–4 alkynyl”). In some embodiments, an alkynyl group has 2 to 3 carbon atoms (“C _2–3 alkynyl”). In some embodiments, an alkynyl group has 2 carbon atoms (“C ₂ alkynyl”). The one or more carbon– carbon triple bonds can be internal (such as in 2–butynyl) or terminal (such as in 1–butynyl). Examples of C _2–4 alkynyl groups include, without limitation, ethynyl (C ₂ ), 1–propynyl (C ₃ ), 2–propynyl (C ₃ ), 1–butynyl (C ₄ ), 2–butynyl (C ₄ ), and the like. Examples of C _2–6 alkenyl groups include the aforementioned C _2–4 alkynyl groups as well as pentynyl (C ₅ ), hexynyl (C ₆ ), and the like. Additional examples of alkynyl include heptynyl (C ₇ ), octynyl (C ₈ ), and the like. Unless otherwise specified, each instance of an alkynyl group is independently optionally substituted, i.e., unsubstituted (an “unsubstituted alkynyl”) or substituted (a “substituted alkynyl”) with one or more substituents; e.g., for instance from 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. In certain embodiments, the alkynyl group is unsubstituted C _2–10 alkynyl. In certain embodiments, the alkynyl group is substituted C _2–10 alkynyl. [0043] The term “heteroalkyl,” as used herein, refers to an alkyl group, as defined herein, which further comprises 1 or more (e.g., 1, 2, 3, or 4) heteroatoms (e.g., oxygen, sulfur, nitrogen, boron, silicon, phosphorus) within the parent chain, wherein the one or more heteroatoms is inserted between adjacent carbon atoms within the parent carbon chain and/or one or more heteroatoms is inserted between a carbon atom and the parent molecule, i.e., between the point of attachment. In certain embodiments, a heteroalkyl group refers to a saturated group having from 1 to 10 carbon atoms and 1, 2, 3, or 4 heteroatoms (“heteroC _1–10 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 9 carbon atoms and 1, 2, 3, or 4 heteroatoms (“heteroC _1–9 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 8 carbon atoms and 1, 2, 3, or 4 heteroatoms (“heteroC _1–8 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 7 carbon atoms and 1, 2, 3, or 4 heteroatoms (“heteroC _1–7 alkyl”). In some embodiments, a heteroalkyl group is a group having 1 to 6 carbon atoms and 1, 2, or 3 heteroatoms (“heteroC _1–6 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 5 carbon atoms and 1 or 2 heteroatoms (“heteroC _1–5 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 4 carbon atoms and 1 or 2 heteroatoms (“heteroC _1–4 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 3 carbon atoms and 1 heteroatom (“heteroC _1–3 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 to 2 carbon atoms and 1 heteroatom (“heteroC _1–2 alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 1 carbon atom and 1 heteroatom (“heteroC ₁ alkyl”). In some embodiments, a heteroalkyl group is a saturated group having 2 to 6 carbon atoms and 1 or 2 heteroatoms (“heteroC _2–6 alkyl”). Unless otherwise specified, each instance of a heteroalkyl group is independently unsubstituted (an “unsubstituted heteroalkyl”) or substituted (a “substituted heteroalkyl”) with one or more substituents. In certain embodiments, the heteroalkyl group is an unsubstituted heteroC _1–10 alkyl. In certain embodiments, the heteroalkyl group is a substituted heteroC _1–10 alkyl. Exemplary heteroalkyl groups include: –CH ₂ OH, –CH ₂ OCH ₃ , –CH ₂ NH ₂ , –CH ₂ NH(CH ₃ ), –CH ₂ N(CH ₃ ) ₂ , –CH ₂ CH ₂ OH, –CH ₂ CH ₂ OCH ₃ , –CH ₂ CH ₂ NH ₂ , – CH ₂ CH ₂ NH(CH ₃ ), –CH ₂ CH ₂ N(CH ₃ ) ₂ . [0044] “Aryl” refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 ʌ electrons shared in a cyclic array) having 6–14 ring carbon atoms and zero heteroatoms provided in the aromatic ring system (“C _6–14 aryl”). In some embodiments, an aryl group has six ring carbon atoms (“C ₆ aryl”; e.g., phenyl). In some embodiments, an aryl group has ten ring carbon atoms (“C ₁₀ aryl”; e.g., naphthyl such as 1–naphthyl and 2–naphthyl). In some embodiments, an aryl group has fourteen ring carbon atoms (“C ₁₄ aryl”; e.g., anthracyl). “Aryl” also includes ring systems wherein the aryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the radical or point of attachment is on the aryl ring, and in such instances, the number of carbon atoms continue to designate the number of carbon atoms in the aryl ring system. Particularly aryl groups include phenyl, naphthyl, indenyl, and tetrahydronaphthyl. Unless otherwise specified, each instance of an aryl group is independently optionally substituted, i.e., unsubstituted (an “unsubstituted aryl”) or substituted (a “substituted aryl”) with one or more substituents. In certain embodiments, the aryl group is unsubstituted C _6–14 aryl. In certain embodiments, the aryl group is substituted C _6–14 aryl. [0045] In certain embodiments, an aryl group is substituted with one or more of groups selected from halo, C ₁ –C ₈ alkyl, C ₁ –C ₈ haloalkyl, cyano, hydroxy, C ₁ –C ₈ alkoxy, and amino. [0046] Examples of representative substituted aryls include the following wherein one of R ⁵⁶ and R ⁵⁷ may be hydrogen and at least one of R ⁵⁶ and R ⁵⁷ is each independently selected from C ₁ –C ₈ alkyl, C ₁ –C ₈ haloalkyl, 4-10 membered heterocyclyl, alkanoyl, C ₁ –C ₈ alkoxy, heteroaryloxy, alkylamino, arylamino, heteroarylamino, – NR ⁵⁸ COR ⁵⁹ , –NR ⁵⁸ SOR ⁵⁹ NR ⁵⁸ SO ₂ R ⁵⁹ , –COOalkyl, –COOaryl, –CONR ⁵⁸ R ⁵⁹ , – CONR ⁵⁸ OR ⁵⁹ , –NR ⁵⁸ R ⁵⁹ , –SO ₂ NR ⁵⁸ R ⁵⁹ , –S-alkyl, –SOalkyl, –SO ₂ alkyl, –Saryl, –SOaryl, – SO ₂ aryl; or R ⁵⁶ and R ⁵⁷ may be joined to form a cyclic ring (saturated or unsaturated) from 5 to 8 atoms, optionally containing one or more heteroatoms selected from the group consisting of N, O, or S. R ⁶⁰ and R ⁶¹ are independently hydrogen, –C ₁ –C ₈ alkyl, –C ₁ –C ₄ haloalkyl, –C ₃ – C ₁₀ cycloalkyl, 4-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, substituted C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, or substituted 5-10 membered heteroaryl. “Fused aryl” refers to an aryl having two of its ring carbons in common with a second aryl or heteroaryl ring or with a carbocyclyl or heterocyclyl ring. [0047] “Heteroaryl” refers to a radical of a 5–10 membered monocyclic or bicyclic 4n+2 aromatic ring system (e.g., having 6 or 10 ʌ electrons shared in a cyclic array) having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen and sulfur (“5–10 membered heteroaryl”). In heteroaryl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. Heteroaryl bicyclic ring systems can include one or more heteroatoms in one or both rings. “Heteroaryl” includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the point of attachment is on the heteroaryl ring, In such instances, unless otherwise specified, the number of ring members continue to designate the number of ring members in the heteroaryl ring system. “Heteroaryl” also includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more aryl groups wherein the point of attachment is either on the aryl or heteroaryl ring, and in such instances, the number of ring members designates the number of ring members in the fused (aryl/heteroaryl) ring system. Bicyclic heteroaryl groups wherein one ring does not contain a heteroatom (e.g., indolyl, quinolinyl, carbazolyl, and the like) the point of attachment can be on either ring, i.e., either the ring bearing a heteroatom (e.g., 2–indolyl) or the ring that does not contain a heteroatom (e.g., 5–indolyl). [0048] In some embodiments, a heteroaryl group is a 5–10 membered aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–10 membered heteroaryl”). In some embodiments, a heteroaryl group is a 5–8 membered aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–8 membered heteroaryl”). In some embodiments, a heteroaryl group is a 5–6 membered aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–6 membered heteroaryl”). In some embodiments, the 5-6 membered heteroaryl has 1-3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heteroaryl has 1-2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heteroaryl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. Unless otherwise specified, each instance of a heteroaryl group is independently optionally substituted, i. e. , unsubstituted (an “unsubstituted heteroaryl”) or substituted (a “substituted heteroaryl”) with one or more substituents. In certain embodiments, the heteroaryl group is unsubstituted 5-14 membered heteroaryl. In certain embodiments, the heteroaryl group is substituted 5-14 membered heteroaryl. In some embodiments, a heteroaryl group is a bicyclic 8-12 membered aromatic ring system having ring carbon atoms and 1-6 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“8-12 membered bicyclic heteroaryl”). In some embodiments, a heteroaryl group is an 8-10 membered bicyclic aromatic ring system having ring carbon atoms and 1-6 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“8-10 membered bicyclic heteroaryl”). In some embodiments, a heteroaryl group is a 9-10 membered bicyclic aromatic ring system having ring carbon atoms and 1-6 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“9-10 membered bicyclic heteroaryl”). Unless otherwise specified, each instance of a heteroaryl group is independently unsubstituted (an “unsubstituted heteroaryl”) or substituted (a “substituted heteroaryl”) with one or more substituents. In certain embodiments, the heteroaryl group is an unsubstituted 5-14 membered heteroaryl. In certain embodiments, the heteroaryl group is a substituted 5-14 membered heteroaryl.

[0049] Exemplary 5-membered heteroaryl groups containing one heteroatom include, without limitation, pyrrolyl, furanyl and thiophenyl. Exemplary 5-membered heteroaryl groups containing two heteroatoms include, without limitation, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5-membered heteroaryl groups containing three heteroatoms include, without limitation, triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary 5-membered heteroaryl groups containing four heteroatoms include, without limitation, tetrazolyl. Exemplary 6-membered heteroaryl groups containing one heteroatom include, without limitation, pyridinyl. Exemplary 6-membered heteroaryl groups containing two heteroatoms include, without limitation, pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6–membered heteroaryl groups containing three or four heteroatoms include, without limitation, triazinyl and tetrazinyl, respectively. Exemplary 7–membered heteroaryl groups containing one heteroatom include, without limitation, azepinyl, oxepinyl, and thiepinyl. Exemplary 5,6–bicyclic heteroaryl groups include, without limitation, indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzoisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzthiazolyl, benzisothiazolyl, benzthiadiazolyl, indolizinyl, and purinyl. Exemplary 6,6– bicyclic heteroaryl groups include, without limitation, naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl. [0050] Examples of representative heteroaryls include the following: wherein each Z is selected from carbonyl, N, NR ⁶⁵ , O, and S; and R ⁶⁵ is independently hydrogen, –C ₁ –C ₈ alkyl, C ₃ –C ₁₀ cycloalkyl, 4-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, and 5- 10 membered heteroaryl. [0051] In the structures described herein, a substituent attached to a polycyclic (e.g., bicyclic or tricyclic) cycloalkyl, heterocyclyl, aryl or heteroaryl with a bond that spans two or more rings is understood to mean that the substituent can be attached at any position in each of the rings. [0052] “Heteroaralkyl” or “heteroarylalkyl” is a subset of “alkyl” and refers to an alkyl group substituted by a heteroaryl group (e.g., a 5-10 membered heteroaryl containing 1, 2 or 3 heteroatoms selected from O, N and S and oxidized forms thereof), wherein the point of attachment is on the alkyl moiety. In some embodiments, a heteroarylalkyl is a C _1-2 alkyl- heteroaryl (e.g., –CH ₂ -heteroaryl, –CH ₂ CH ₂ -heteroaryl, –CH(CH ₃ )-heteroaryl). In some embodiments, a heteroarylalkyl is a –CH ₂ -heteroaryl. Typical heteroarylalkyl groups include, but are not limited to, pyridinylmethyl, pyrimidinylmethyl, furanylmethyl, thiophenylmethyl, pyrrolylmethyl, pyrazolylmethyl, imidazolylmethyl, thiazolylmethyl, oxazolylmethyl, thiazolylmethyl, pyridinylethyl, pyrimidinylethyl, furanylethyl, thiophenylethyl, pyrrolylethyl, pyrazolylethyl, imidazolylethyl, thiazolylethyl, oxazolylethyl, thiazolylethyl and the like. [0053] The term “carbocyclyl” or “carbocyclic” refers to a radical of a non-aromatic monocyclic, bicyclic, or tricyclic or polycyclic hydrocarbon ring system having from 3 to 14 ring carbon atoms (“C _3-14 carbocyclyl”) and zero heteroatoms in the non-aromatic ring system. Carbocyclyl groups include fully saturated ring systems (e.g., cycloalkyls), and partially saturated ring systems. In some embodiments, a carbocyclyl group has 3 to 10 ring carbon atoms (“C _3–10 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 8 ring carbon atoms (“C _3-8 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 7 ring carbon atoms (“C _3-7 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 6 ring carbon atoms (“C _3-6 carbocyclyl”). In some embodiments, a carbocyclyl group has 4 to 6 ring carbon atoms (“C _4-6 carbocyclyl”). In some embodiments, a carbocyclyl group has 5 to 6 ring carbon atoms (“C _5-6 carbocyclyl”). In some embodiments, a carbocyclyl group has 5 to 10 ring carbon atoms (“C _5-10 carbocyclyl”). Exemplary C _3-6 carbocyclyl groups include, without limitation, cyclopropyl (C ₃ ), cyclopropenyl (C ₃ ), cyclobutyl (C4), cyclobutenyl (C ₄ ), cyclopentyl (C ₅ ), cyclopentenyl (C ₅ ), cyclohexyl (C ₆ ), cyclohexenyl (C ₆ ), cyclohexadienyl (C ₆ ), and the like. Exemplary C _3-8 carbocyclyl groups include, without limitation, the aforementioned C _3-6 carbocyclyl groups as well as cycloheptyl (C ₇ ), cycloheptenyl (C ₇ ), cycloheptadienyl (C ₇ ), cycloheptatrienyl (C ₇ ), cyclooctyl (C ₈ ), cyclooctenyl (C ₈ ), bicyclo[2.2.1]heptanyl (C ₇ ), bicyclo[2.2.2]octanyl (C ₈ ), and the like. Exemplary C _3-10 carbocyclyl groups include, without limitation, the aforementioned C _3-8 carbocyclyl groups as well as cyclononyl (C ₉ ), cyclononenyl (C ₉ ), cyclodecyl (C ₁₀ ), cyclodecenyl (C ₁₀ ), octahydro-1H-indenyl (C ₉ ), decahydronaphthalenyl (C ₁₀ ), spiro[4.5]decanyl (C ₁₀ ), and the like. [0054] As the foregoing examples illustrate, in certain embodiments, the carbocyclyl group is either monocyclic (“monocyclic carbocyclyl”) or polycyclic (e.g., containing a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic carbocyclyl”) or tricyclic system (“tricyclic carbocyclyl”)) and can be saturated or can contain one or more carbon- carbon double or triple bonds. “Carbocyclyl” also includes ring systems wherein the carbocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups wherein the point of attachment is on the carbocyclyl ring, and in such instances, the number of carbons continue to designate the number of carbons in the carbocyclic ring system. Unless otherwise specified, each instance of a carbocyclyl group is independently unsubstituted (an “unsubstituted carbocyclyl”) or substituted (a “substituted carbocyclyl”) with one or more substituents. In certain embodiments, the carbocyclyl group is an unsubstituted C _3-14 carbocyclyl. In certain embodiments, the carbocyclyl group is a substituted C _3-14 carbocyclyl. [0055] The term “cycloalkyl” as employed herein includes saturated cyclic, bicyclic, tricyclic, or polycyclic hydrocarbon groups having 3 to 14 carbons containing the indicated number of rings and carbon atoms (for example a C ₃ –C ₁₄ monocyclic, C ₄ –C ₁₄ bicyclic, C ₅ – C ₁₄ tricyclic, or C ₆ –C ₁₄ polycyclic cycloalkyl). In some embodiments “cycloalkyl” is a monocyclic cycloalkyl. In some embodiments, a monocyclic cycloalkyl has 3-14 ring carbon atoms. (“C _3-14 monocyclic cycloalkyl”). In some embodiments, a monocyclic cycloalkyl group has 3 to 10 ring carbon atoms (“C _3–10 monocyclic cycloalkyl”). In some embodiments, a monocyclic cycloalkyl group has 3 to 8 ring carbon atoms (“C _3-8 monocyclic cycloalkyl”). In some embodiments, a monocyclic cycloalkyl group has 3 to 6 ring carbon atoms (“C _3-6 monocyclic cycloalkyl”). In some embodiments, a monocyclic cycloalkyl group has 4 to 6 ring carbon atoms (“C4-6 monocyclic cycloalkyl”). In some embodiments, a monocyclic cycloalkyl group has 5 to 6 ring carbon atoms (“C _5-6 monocyclic cycloalkyl”). In some embodiments, a monocyclic cycloalkyl group has 5 to 10 ring carbon atoms (“C _5-10 monocyclic cycloalkyl”). Examples of monocyclic C _5-6 cycloalkyl groups include cyclopentyl (C ₅ ) and cyclohexyl (C ₅ ). Examples of C _3-6 cycloalkyl groups include the aforementioned C _5-6 cycloalkyl groups as well as cyclopropyl (C ₃ ) and cyclobutyl (C ₄ ). Examples of C _3-8 cycloalkyl groups include the aforementioned C _3-6 cycloalkyl groups as well as cycloheptyl (C ₇ ) and cyclooctyl (C ₈ ). [0056] In some embodiments “cycloalkyl” is a bicyclic cycloalkyl. In some embodiments, a bicyclic cycloalkyl has 4-14 ring carbon atoms. (“C _4-14 bicyclic cycloalkyl”). In some embodiments, a bicyclic cycloalkyl group has 4 to 12 ring carbon atoms (“C _4-12 bicyclic cycloalkyl”). In some embodiments, a bicyclic cycloalkyl group has 4 to 10 ring carbon atoms (“C _4-10 bicyclic cycloalkyl”). In some embodiments, a bicyclic cycloalkyl group has 5 to 10 ring carbon atoms (“C _5-10 bicyclic cycloalkyl”). In some embodiments, a bicyclic cycloalkyl group has 6 to 10 ring carbon atoms (“C _6-10 bicyclic cycloalkyl”). In some embodiments, a bicyclic cycloalkyl group has 8 to 10 ring carbon atoms (“C _8-10 bicyclic cycloalkyl”). In some embodiments, a bicyclic cycloalkyl group has 7 to 9 ring carbon atoms (“C _7-9 bicyclic cycloalkyl”). Examples of bicyclic cycloalkyls include bicyclo[1.1.0]butane (C ₄ ), bicyclo[1.1.1]pentane (C ₅ ), spiro[2.2] pentane (C ₅ ), bicyclo[2.1.0]pentane (C ₅ ), bicyclo[2.1.1]hexane (C ₆ ), bicyclo[3.1.0]hexane (C ₆ ), spiro[2.3] hexane (C ₆ ), bicyclo[2.2.1]heptane (norbornane) (C ₇ ), bicyclo[3.2.0]heptane (C ₇ ), bicyclo[3.1.1]heptane (C ₇ ), bicyclo[3.1.1]heptane (C ₇ ), bicyclo[4.1.0]heptane (C ₇ ), spiro[2.4] heptane (C ₇ ), spiro [3.3] heptane (C ₇ ), bicyclo[2.2.2]octane (C ₈ ), bicyclo[4.1.1]octane (C ₈ )octahydropentalene (C ₈ ), bicyclo[3.2.1]octane (C ₈ ), bicyclo[4.2.0]octane (C ₈ ), spiro[2.5]octane (C ₈ ), spiro[3.4]octane (C ₈ ), bicyclo[3.3.1]nonane (C ₉ ), octahydro-1H-indene (C ₉ ), bicyclo[4.2.1]nonane (C ₉ ), spiro[3.5]nonane (C ₉ ), spiro[4.4]nonane (C ₉ ), bicyclo[3.3.2]decane (C ₁₀ ), bicyclo[4.3.1]decane (C ₁₀ ), spiro[4.5]decane (C ₁₀ ), bicyclo[3.3.3]undecane (C ₁₁ ), decahydronaphthalene (C ₁₀ ), bicyclo[4.3.2]undecane (C ₁₁ ), spiro[5.5]undecane (C ₁₁ ) and bicyclo[4.3.3]dodecane (C ₁₂ ). In some embodiments “cycloalkyl” is a tricyclic cycloalkyl. In some embodiments, a tricyclic cycloalkyl has 6-14 ring carbon atoms. (“C _6-14 tricyclic cycloalkyl”). In some embodiments, a tricyclic cycloalkyl group has 8 to 12 ring carbon atoms (“C _8-12 tricyclic cycloalkyl”). In some embodiments, a tricyclic cycloalkyl group has 10 to 12 ring carbon atoms (“C _10-12 tricyclic cycloalkyl. Examples of tricyclic cycloalkyls include adamantine (C ₁₂ ). [0057] Unless otherwise specified, each instance of a cycloalkyl group is independently unsubstituted (an “unsubstituted cycloalkyl”) or substituted (a “substituted cycloalkyl”) with one or more substituents. In certain embodiments, the cycloalkyl group is an unsubstituted C _3-14 cycloalkyl. In certain embodiments, the cycloalkyl group is a substituted C _3-14 cycloalkyl [0058] “Heterocyclyl” or “heterocyclic” refers to a radical of a 3– to 10–membered non– aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon (“3–10 membered heterocyclyl”). In some embodiments, the heterocyclyl is a 3- to 10- membered non-aromatic ring system having ring carbon atoms and 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and sulfur, including oxidized forms thereof. In heterocyclyl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. A heterocyclyl group can either be monocyclic (“monocyclic heterocyclyl”) or a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic heterocyclyl”), and can be saturated or can be partially unsaturated. Heterocyclyl bicyclic ring systems can include one or more heteroatoms in one or both rings. “Heterocyclyl” also includes ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more carbocyclyl groups wherein the point of attachment is either on the carbocyclyl or heterocyclyl ring, or ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups, wherein the point of attachment is on the heterocyclyl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heterocyclyl ring system. Unless otherwise specified, each instance of heterocyclyl is independently optionally substituted, i.e., unsubstituted (an “unsubstituted heterocyclyl”) or substituted (a “substituted heterocyclyl”) with one or more substituents. In certain embodiments, the heterocyclyl group is unsubstituted 3–10 membered heterocyclyl. In certain embodiments, the heterocyclyl group is substituted 3–10 membered heterocyclyl. [0059] In some embodiments, a heterocyclyl group is a 5–10 membered non–aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon (“5–10 membered heterocyclyl”). In some embodiments, a heterocyclyl group is a 5–8 membered non–aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–8 membered heterocyclyl”). In some embodiments, a heterocyclyl group is a 5–6 membered non–aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–6 membered heterocyclyl”). In some embodiments, the 5–6 membered heterocyclyl has 1–3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5–6 membered heterocyclyl has 1–2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5–6 membered heterocyclyl has one ring heteroatom selected from nitrogen, oxygen, and sulfur. [0060] Exemplary 3–membered heterocyclyl groups containing one heteroatom include, without limitation, aziridinyl, oxiranyl, thiorenyl. Exemplary 4–membered heterocyclyl groups containing one heteroatom include, without limitation, azetidinyl, oxetanyl and thietanyl. Exemplary 5–membered heterocyclyl groups containing one heteroatom include, without limitation, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl and pyrrolyl–2,5–dione. Exemplary 5– membered heterocyclyl groups containing two heteroatoms include, without limitation, dioxolanyl, oxasulfuranyl, disulfuranyl, and oxazolidin-2-one. Exemplary 5–membered heterocyclyl groups containing three heteroatoms include, without limitation, triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6–membered heterocyclyl groups containing one heteroatom include, without limitation, piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl. Exemplary 6–membered heterocyclyl groups containing two heteroatoms include, without limitation, piperazinyl, morpholinyl, dithianyl, dioxanyl. Exemplary 6– membered heterocyclyl groups containing two heteroatoms include, without limitation, triazinanyl. Exemplary 7–membered heterocyclyl groups containing one heteroatom include, without limitation, azepanyl, oxepanyl and thiepanyl. Exemplary 8–membered heterocyclyl groups containing one heteroatom include, without limitation, azocanyl, oxecanyl and thiocanyl. Exemplary 5-membered heterocyclyl groups fused to a C6 aryl ring (also referred to herein as a 5,6-bicyclic heterocyclic ring) include, without limitation, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, benzoxazolinonyl, and the like. Exemplary bicyclic heterocyclyl groups include, without limitation, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, tetrahydrobenzothienyl, tetrahydrobenzofuranyl, tetrahydroindolyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, decahydroisoquinolinyl, octahydrochromenyl, octahydroisochromenyl, decahydronaphthyridinyl, decahydro-1,8-naphthyridinyl, octahydropyrrolo[3,2-b]pyrrole, indolinyl, phthalimidyl, naphthalimidyl, chromanyl, chromenyl, 1H-benzo[e][1,4]diazepinyl, 1,4,5,7-tetrahydropyrano[3,4-b]pyrrolyl, 5,6-dihydro-4H-furo[3,2-b]pyrrolyl, 6,7-dihydro- 5H-furo[3,2-b]pyranyl, 5,7-dihydro-4H-thieno[2,3-c]pyranyl, 2,3-dihydro-1H-pyrrolo[2,3- b]pyridinyl, 2,3-dihydrofuro[2,3-b]pyridinyl, 4,5,6,7-tetrahydro-1H-pyrrolo[2,3-b]pyridinyl, 4,5,6,7-tetrahydrofuro[3,2-c]pyridinyl, 4,5,6,7-tetrahydrothieno[3,2-b]pyridinyl, 1,2,3,4- tetrahydro-1,6-naphthyridinyl, and the like. Exemplary 6-membered heterocyclyl groups fused to an aryl ring (also referred to herein as a 6,6-bicyclic heterocyclic ring) include, without limitation, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and the like. “Nitrogen-containing heterocyclyl” group means a 4– to 7– membered non-aromatic cyclic group containing at least one nitrogen atom, for example, but without limitation, morpholine, piperidine (e.g., 2-piperidinyl, 3-piperidinyl and 4-piperidinyl), pyrrolidine (e.g., 2- pyrrolidinyl and 3-pyrrolidinyl), azetidine, pyrrolidone, imidazoline, imidazolidinone, 2- pyrazoline, pyrazolidine, piperazine, and N-alkyl piperazines such as N-methyl piperazine. Particular examples include azetidine, piperidone and piperazone. [0061] “Hetero” when used to describe a compound or a group present on a compound means that one or more carbon atoms in the compound or group have been replaced by a nitrogen, oxygen, or sulfur heteroatom. Hetero may be applied to any of the hydrocarbyl groups described above such as alkyl, e.g., heteroalkyl, cycloalkyl, e.g., heterocyclyl, aryl, e.g., heteroaryl, cycloalkenyl, e.g., cycloheteroalkenyl, and the like having from 1 to 5, and particularly from 1 to 3 heteroatoms. [0062] “Acyl” refers to a radical –C(=O)R ²⁰ , where R ²⁰ is hydrogen, substituted or unsubstitued alkyl, substituted or unsubstitued alkenyl, substituted or unsubstitued alkynyl, substituted or unsubstitued carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstitued heteroaryl, as defined herein. “Alkanoyl” is an acyl group wherein R ²⁰ is a group other than hydrogen. Representative acyl groups include, but are not limited to, formyl (–CHO), acetyl (–C(=O)CH ₃ ), cyclohexylcarbonyl, cyclohexylmethylcarbonyl, benzoyl (–C(=O)Ph), benzylcarbonyl (–C(=O)CH ₂ Ph), ––C(=O)– C ₁ –C ₈ alkyl, –C(=O)-(CH ₂ ) _t (C ₆ –C ₁₀ aryl), –C(=O)-(CH ₂ ) _t (5-10 membered heteroaryl), – C(=O)-(CH ₂ ) _t (C ₃ –C ₁₀ cycloalkyl), and –C(=O)-(CH ₂ ) _t (4-10 membered heterocyclyl), wherein t is an integer from 0 to 4. In certain embodiments, R ²¹ is C ₁ –C ₈ alkyl, substituted with halo or hydroxy; or C ₃ –C ₁₀ cycloalkyl, 4-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, arylalkyl, 5-10 membered heteroaryl or heteroarylalkyl, each of which is substituted with unsubstituted C ₁ – C ₄ alkyl, halo, unsubstituted C ₁ –C ₄ alkoxy, unsubstituted C ₁ –C ₄ haloalkyl, unsubstituted C ₁ – C ₄ hydroxyalkyl, or unsubstituted C ₁ –C ₄ haloalkoxy or hydroxy. [0063] The term aminoalkyl refers to a substituted alkyl group wherein one or more of the hydrogen atoms are independently replaced by an –NH ₂ group. [0064] The term hydroxyalkyl refers to a substituted alkyl group wherein one or more of the hydrogen atoms are independently replaced by an –OH group. [0065] The terms “alkylamino” and “dialkylamino” refer to –NH(alkyl) and–N(alkyl) ₂ radicals respectively. In some embodiments the alkylamino is a–NH(C ₁ –C ₄ alkyl). In some embodiments the alkylamino is methylamino, ethylamino, propylamino, isopropylamino, n- butylamino, iso-butylamino, sec-butylamino or tert-butylamino. In some embodiments the dialkylamino is–N( C ₁ –C ₆ alkyl) ₂ . In some embodiments the dialkylamino is a dimethylamino, a methylethylamino, a diethylamino, a methylpropylamino, a methylisopropylamino, a methylbutylamino, a methylisobutylamino or a methyltertbutylamino. [0066] The term “aryloxy” refers to an –O–aryl radical. In some embodiments the aryloxy group is phenoxy. [0067] The term “haloalkoxy” refers to alkoxy structures that are substituted with one or more halo groups or with combinations thereof. For example, the term “fluoroalkoxy” includes haloalkoxy groups, in which the halo is fluorine. In some embodiments haloalkoxy groups are difluoromethoxy and trifluoromethoxy. [0068] “Alkoxy” refers to the group –OR ²⁹ where R ²⁹ is substituted or unsubstituted alkyl, substituted or unsubstitued alkenyl, substituted or unsubstitued alkynyl, substituted or unsubstitued carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstitued heteroaryl. Particular alkoxy groups are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n- hexoxy, and 1,2-dimethylbutoxy. Particular alkoxy groups are lower alkoxy, i.e. with between 1 and 6 carbon atoms. Further particular alkoxy groups have between 1 and 4 carbon atoms. In certain embodiments, R ²⁹ is a group that has 1 or more substituents, for instance from 1 to 5 substituents, and particularly from 1 to 3 substituents, in particular 1 substituent, selected from the group consisting of amino, substituted amino, C ₆ –C ₁₀ aryl, aryloxy, carboxyl, cyano, C ₃ –C ₁₀ cycloalkyl, 4-10 membered heterocyclyl, halogen, 5-10 membered heteroaryl, hydroxyl, nitro, thioalkoxy, thioaryloxy, thiol, alkyl-S(O)-, aryl–S(O)-, alkyl–S(O) ₂ – and aryl-S(O) ₂ -. Exemplary ‘substituted alkoxy’ groups include, but are not limited to, –O– (CH ₂ ) _t (C ₆ –C ₁₀ aryl), –O–(CH ₂ ) _t (5-10 membered heteroaryl), –O–(CH ₂ ) _t (C ₃ –C ₁₀ cycloalkyl), and –O–(CH ₂ ) _t (4-10 membered heterocyclyl), wherein t is an integer from 0 to 4 and any aryl, heteroaryl, cycloalkyl or heterocyclyl groups present, may themselves be substituted by unsubstituted C ₁ –C ₄ alkyl, halo, unsubstituted C ₁ –C ₄ alkoxy, unsubstituted C ₁ –C ₄ haloalkyl, unsubstituted C ₁ –C ₄ hydroxyalkyl, or unsubstituted C ₁ –C ₄ haloalkoxy or hydroxy. Particular exemplary ‘substituted alkoxy’ groups are –OCF ₃ , –OCH ₂ CF ₃ , –OCH ₂ Ph, –OCH ₂ - cyclopropyl, –OCH ₂ CH ₂ OH, and –OCH ₂ CH ₂ N(CH ₃ ) ₂ . [0069] “Amino” refers to the radical –NH ₂ . [0070] “Oxo group” refers to –C(=O)–. [0071] “Substituted amino” refers to an amino group of the formula –N(R ³⁸ ) ₂ wherein R ³⁸ is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstitued alkenyl, substituted or unsubstitued alkynyl, substituted or unsubstitued carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstitued heteroaryl, or an amino protecting group, wherein at least one of R ³⁸ is not a hydrogen. In certain embodiments, each R ³⁸ is independently selected from hydrogen, –C ₁ –C ₈ alkyl, – C ₃ –C ₈ alkenyl, –C ₃ –C ₈ alkynyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, 4-10 membered heterocyclyl, or C ₃ –C ₁₀ cycloalkyl; or C ₁ –C ₈ alkyl, substituted with halo or hydroxy; C ₃ –C ₈ alkenyl, substituted with halo or hydroxy; C ₃ –C ₈ alkynyl, substituted with halo or hydroxy, or –(CH ₂ ) _t (C ₆ –C ₁₀ aryl), –(CH ₂ ) _t (5-10 membered heteroaryl), –(CH ₂ ) _t (C ₃ –C ₁₀ cycloalkyl), or – (CH ₂ ) _t (4-10 membered heterocyclyl), wherein t is an integer between 0 and 8, each of which is substituted by unsubstituted C ₁ –C ₄ alkyl, halo, unsubstituted C ₁ –C ₄ alkoxy, unsubstituted C ₁ –C ₄ haloalkyl, unsubstituted C ₁ –C ₄ hydroxyalkyl, or unsubstituted C ₁ –C ₄ haloalkoxy or hydroxy; or both R ³⁸ groups are joined to form an alkylene group. [0072] Exemplary “substituted amino” groups include, but are not limited to, –NR ³⁹ – C ₁ –C ₈ alkyl, –NR ³⁹ -(CH ₂ ) _t (C ₆ –C ₁₀ aryl), –NR ³⁹ -(CH ₂ ) _t (5-10 membered heteroaryl), –NR ³⁹ - (CH ₂ ) _t (C ₃ –C ₁₀ cycloalkyl), and –NR ³⁹ -(CH ₂ ) _t (4-10 membered heterocyclyl), wherein t is an integer from 0 to 4, for instance 1 or 2, each R ³⁹ independently represents H or C ₁ –C ₈ alkyl; and any alkyl groups present, may themselves be substituted by halo, substituted or unsubstituted amino, or hydroxy; and any aryl, heteroaryl, cycloalkyl, or heterocyclyl groups present, may themselves be substituted by unsubstituted C ₁ –C ₄ alkyl, halo, unsubstituted C ₁ – C ₄ alkoxy, unsubstituted C ₁ –C ₄ haloalkyl, unsubstituted C ₁ –C ₄ hydroxyalkyl, or unsubstituted C ₁ –C ₄ haloalkoxy or hydroxy. For the avoidance of doubt the term ‘substituted amino’ includes the groups alkylamino, substituted alkylamino, alkylarylamino, substituted alkylarylamino, arylamino, substituted arylamino, dialkylamino, and substituted dialkylamino as defined below. Substituted amino encompasses both monosubstituted amino and disubstituted amino groups. [0073] In certain embodiments, the substituent present on the nitrogen atom is a nitrogen protecting group (also referred to herein as an “amino protecting group”). Nitrogen protecting groups include, but are not limited to, –OH, –OR ^aa , –N(R ^cc ) ₂ , –C(=O)R ^aa , –C(=O)N(R ^cc ) ₂ , –CO ₂ R ^aa , –SO ₂ R ^aa , –C(=NR ^cc )R ^aa , –C(=NR ^cc )OR ^aa , –C(=NR ^cc )N(R ^cc ) ₂ , –SO ₂ N(R ^cc ) ₂ , –SO ₂ R ^cc , –SO ₂ OR ^cc , –SOR ^aa , –C(=S)N(R ^cc ) ₂ , –C(=O)SR ^cc , –C(=S)SR ^cc , –C _{1- 10} alkyl (e.g., aralkyl, heteroaralkyl), –C _2–10 alkenyl, –C _2–10 alkynyl, heteroC _1–10 alkyl, heteroC _2–10 alkenyl, heteroC _2–10 alkynyl, C _3–10 carbocyclyl, 3-14 membered heterocyclyl, C _6-14 aryl, and 5-14 membered heteroaryl groups, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aralkyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups, and wherein R ^aa , R ^bb , R ^cc and R ^dd are as defined herein. Nitrogen protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3 ^rd edition, John Wiley & Sons, 1999, incorporated herein by reference. each instance of R ^aa is, independently, selected from –C _1-10 alkyl, –C _1-10 perhaloalkyl, –C _2-10 alkenyl, –C _2-10 alkynyl, heteroC _1-10 alkyl, heteroC _2-10 alkenyl, heteroC _2-10 alkynyl, C _3-10 carbocyclyl, 3-14 membered heterocyclyl, C _6-14 aryl, and 5-14 membered heteroaryl, or two R ^aa groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups; each instance of R ^bb is, independently, selected from hydrogen, –OH, –OR ^aa , –N(R ^cc ) ₂ , –CN, –C(=O)R ^aa , –C(=O)N(R ^cc ) ₂ , –CO ₂ R ^aa , –SO ₂ R ^aa , –C(=NR ^cc )OR ^aa , –C(=NR ^cc )N(R ^cc ) ₂ , –SO ₂ N(R ^cc ) ₂ , –SO ₂ R ^cc , –SO ₂ OR ^cc , –SOR ^aa , –C(=S)N(R ^cc ) ₂ , –C(=O)SR ^cc , –C(=S)SR ^cc , –P(=O)(R ^aa ) ₂ , –P(=O)(OR ^cc ) ₂ , –P(=O)(N(R ^cc ) ₂ ) ₂ , –C _1–10 alkyl, –C _1–10 perhaloalkyl, –C _2–10 alkenyl, –C _2–10 alkynyl, heteroC _1–10 alkyl, heteroC _2–10 alkenyl, heteroC _2–10 alkynyl, C _3–10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two R ^bb groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups; wherein X- is a counterion. each instance of R ^cc is, independently, selected from hydrogen, –C _1-10 alkyl, –C _1-10 perhaloalkyl, –C _2-10 alkenyl, –C _2-10 alkynyl, heteroC _1-10 alkyl, heteroC _2-10 alkenyl, heteroC _2-10 alkynyl, C _3-10 carbocyclyl, 3-14 membered heterocyclyl, C _6-14 aryl, and 5-14 membered heteroaryl, or two R ^cc groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups; each instance of R ^dd is, independently, selected from halogen, –CN, –NO ₂ , –N ₃ , –SO ₂ H, –SO ₃ H, –OH, –OR ^ee , –ON(R ^ff ) ₂ , –N(R ^ff ) ₂ , –N(R ^ff ) ₃ ⁺ X-, –N(OR ^ee )R ^ff , –SH, –SR ^ee , –SSR ^ee , –C(=O)R ^ee , –CO ₂ H, –CO ₂ R ^ee , –OC(=O)R ^ee , –OCO ₂ R ^ee , –C(=O)N(R ^ff ) ₂ , –OC(=O)N(R ^ff ) ₂ , –NR ^ff C(=O)R ^ee , –NR ^ff CO ₂ R ^ee , –NR ^ff C(=O)N(R ^ff ) ₂ , –C(=NR ^ff )OR ^ee , –OC(=NR ^ff )R ^ee , –OC(=NR ^ff )OR ^ee , –C(=NR ^ff )N(R ^ff ) ₂ , –OC(=NR ^ff )N(R ^ff ) ₂ , –NR ^ff C(=NR ^ff )N(R ^ff ) ₂ , _íNR ^ff _SO2R ^ee _, ^íSO _2N(R ^ff _)2, ^íSO _2R ^ee _, ^íSO _2OR ^ee _, ^íOSO _2R ^ee _, ^íS(=O)Ree _, ^íSi(Ree _)3, –OSi(R ^ee ) ₃ , –C(=S)N(R ^ff ) ₂ , –C(=O)SR ^ee , –C(=S)SR ^ee , –SC(=S)SR ^ee , –P(=O)(OR ^ee ) ₂ , –P(=O)(R ^ee ) ₂ , –OP(=O)(R ^ee ) ₂ , –OP(=O)(OR ^ee ) ₂ , –C _1-6 alkyl, –C _1-6 perhaloalkyl, –C _2-6 alkenyl, –C _2-6 alkynyl, heteroC _1-6 alkyl, heteroC _2-6 alkenyl, heteroC _2-6 alkynyl, C _3–10 carbocyclyl, 3-10 membered heterocyclyl, C _6-10 aryl, 5-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^gg groups, or two geminal R ^dd substituents can be joined to form =O or =S; wherein X- is a counterion; each instance of R ^ee is, independently, selected from –C _1-6 alkyl, –C _1-6 perhaloalkyl, –C _2-6 alkenyl, –C _2-6 alkynyl, heteroC _1-6 alkyl, heteroC _2-6 alkenyl, heteroC _2-6 alkynyl, C _3-10 carbocyclyl, C _6-10 aryl, 3-10 membered heterocyclyl, and 3-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^gg groups; each instance of R ^ff is, independently, selected from hydrogen, –C _1-6 alkyl, –C _1-6 perhaloalkyl, –C _2-6 alkenyl, –C _2-6 alkynyl, heteroC _1-6 alkyl, heteroC _2-6 alkenyl, heteroC ₂ - ₆ alkynyl, C _3–10 carbocyclyl, 3-10 membered heterocyclyl, C _6-10 aryl and 5-10 membered heteroaryl, or two R ^ff groups are joined to form a 3-10 membered heterocyclyl or 5-10 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^gg groups; and each instance of R ^gg is, independently, halogen, –CN, –NO ₂ , –N ₃ , –SO ₂ H, –SO ₃ H, –OH, –OC _1-6 alkyl, –ON(C _1-6 alkyl) ₂ , –N(C _1-6 alkyl) ₂ , –N(C _1-6 alkyl) ₃ ⁺ X-, –NH(C _1-6 alkyl) ₂ ⁺ X-, –NH ₂ (C _1-6 alkyl) ⁺ X-, –NH ₃ ⁺ X-, –N(OC _1-6 alkyl)(C _1-6 alkyl), –N(OH)(C _1-6 alkyl), –NH(OH), –SH, –SC _1-6 alkyl, –SS(C _1-6 alkyl), –C(=O)(C _1-6 alkyl), –CO ₂ H, –CO ₂ (C _1-6 alkyl), –OC(=O)(C _1-6 alkyl), –OCO ₂ (C _1-6 alkyl), –C(=O)NH ₂ , –C(=O)N(C _1-6 alkyl) ₂ , –OC(=O)NH(C _1-6 alkyl), –NHC(=O)(C _1-6 alkyl), –N(C _1-6 alkyl)C(=O)(C _1-6 alkyl), –NHCO ₂ (C _1-6 alkyl), –NHC(=O)N(C _1-6 alkyl) ₂ , –NHC(=O)NH(C _1-6 alkyl), –NHC(=O)NH ₂ , –C(=NH)O(C _1-6 alkyl), –OC(=NH)(C _1-6 alkyl), –OC(=NH)OC _1-6 alkyl, –C(=NH)N(C _1-6 alkyl) ₂ , –C(=NH)NH(C _1-6 alkyl), –C(=NH)NH ₂ , –OC(=NH)N(C _1-6 alkyl) ₂ , –OC(NH)NH(C1- 6 alkyl), –OC(NH)NH ₂ , –NHC(NH)N(C _1-6 alkyl) ₂ , –NHC(=NH)NH ₂ , –NHSO ₂ (C _1-6 alkyl), –SO ₂ N(C _1-6 alkyl) ₂ , –SO ₂ NH(C _1-6 alkyl), –SO ₂ NH ₂ , –SO ₂ C _1-6 alkyl, –SO ₂ OC _1-6 alkyl,–OSO ₂ C _1-6 alkyl, –SOC _1-6 alkyl, –Si(C _1-6 alkyl) ₃ , –OSi(C _1-6 alkyl) ₃ –C(=S)N(C _1-6 alkyl) ₂ , –C(=S)NH(C _1-6 alkyl), –C(=S)NH ₂ , –C(=O)S(C _1-6 alkyl), –C(=S)SC _1-6 alkyl, –SC(=S)SC _1-6 alkyl, –P(=O)(OC _1-6 alkyl) ₂ , –P(=O)(C _1-6 alkyl) ₂ , –OP(=O)(C _1-6 alkyl) ₂ , –OP(=O)(OC _1-6 alkyl) ₂ , –C _1-6 alkyl, –C _1-6 perhaloalkyl, –C _2-6 alkenyl, –C _2-6 alkynyl, heteroC _1-6 alkyl, heteroC _2-6 alkenyl, heteroC _2-6 alkynyl, C _3-10 carbocyclyl, C _6-10 aryl, 3-10 membered heterocyclyl, 5-10 membered heteroaryl; or two geminal R ^gg substituents can be joined to form =O or =S; wherein X- is a counterion. [0074] For example, nitrogen protecting groups such as amide groups (e.g., –C(=O)R ^aa ) include, but are not limited to, formamide, acetamide, chloroacetamide, trichloroacetamide, trifluoroacetamide, phenylacetamide, 3-phenylpropanamide, picolinamide, 3- pyridylcarboxamide, N-benzoylphenylalanyl derivative, benzamide, p-phenylbenzamide, o- nitrophenylacetamide, o-nitrophenoxyacetamide, acetoacetamide, (N’- dithiobenzyloxyacylamino)acetamide, 3-(p-hydroxyphenyl)propanamide, 3-(o- nitrophenyl)propanamide, 2-methyl-2-(o-nitrophenoxy)propanamide, 2-methyl-2-(o- phenylazophenoxy)propanamide, 4-chlorobutanamide, 3-methyl-3-nitrobutanamide, o- nitrocinnamide, N-acetylmethionine derivative, o-nitrobenzamide and o- (benzoyloxymethyl)benzamide. [0075] Nitrogen protecting groups such as carbamate groups (e.g., –C(=O)OR ^aa ) include, but are not limited to, methyl carbamate, ethyl carbamate, 9-fluorenylmethyl carbamate (Fmoc), 9-(2-sulfo)fluorenylmethyl carbamate, 9-(2,7-dibromo)fluorenylmethyl carbamate, 2,7-di-t-butyl-[9-(10,10-dioxo-10,10,10,10-tetrahydrothioxan thyl)]methyl carbamate (DBD- Tmoc), 4-methoxyphenacyl carbamate (Phenoc), 2,2,2-trichloroethyl carbamate (Troc), 2- trimethylsilylethyl carbamate (Teoc), 2-phenylethyl carbamate (hZ), 1-(1-adamantyl)-1- methylethyl carbamate (Adpoc), 1,1-dimethyl-2-haloethyl carbamate, 1,1-dimethyl-2,2- dibromoethyl carbamate (DB-t-BOC), 1,1-dimethyl-2,2,2-trichloroethyl carbamate (TCBOC), 1-methyl-1-(4-biphenylyl)ethyl carbamate (Bpoc), 1-(3,5-di-t-butylphenyl)-1- methylethyl carbamate (t-Bumeoc), 2-(2’– and 4’-pyridyl)ethyl carbamate (Pyoc), 2-(N,N- dicyclohexylcarboxamido)ethyl carbamate, t-butyl carbamate (BOC or Boc), 1-adamantyl carbamate (Adoc), vinyl carbamate (Voc), allyl carbamate (Alloc), 1-isopropylallyl carbamate (Ipaoc), cinnamyl carbamate (Coc), 4-nitrocinnamyl carbamate (Noc), 8-quinolyl carbamate, N-hydroxypiperidinyl carbamate, alkyldithio carbamate, benzyl carbamate (Cbz), p-methoxybenzyl carbamate (Moz), p-nitobenzyl carbamate, p-bromobenzyl carbamate, p- chlorobenzyl carbamate, 2,4-dichlorobenzyl carbamate, 4-methylsulfinylbenzyl carbamate (Msz), 9-anthrylmethyl carbamate, diphenylmethyl carbamate, 2-methylthioethyl carbamate, 2-methylsulfonylethyl carbamate, 2-(p-toluenesulfonyl)ethyl carbamate, [2-(1,3- dithianyl)]methyl carbamate (Dmoc), 4-methylthiophenyl carbamate (Mtpc), 2,4- dimethylthiophenyl carbamate (Bmpc), 2-phosphonioethyl carbamate (Peoc), 2- triphenylphosphonioisopropyl carbamate (Ppoc), 1,1-dimethyl-2-cyanoethyl carbamate, m- chloro-p-acyloxybenzyl carbamate, p-(dihydroxyboryl)benzyl carbamate, 5- benzisoxazolylmethyl carbamate, 2-(trifluoromethyl)-6-chromonylmethyl carbamate (Tcroc), m-nitrophenyl carbamate, 3,5-dimethoxybenzyl carbamate, o-nitrobenzyl carbamate, 3,4- dimethoxy-6-nitrobenzyl carbamate, phenyl (o-nitrophenyl)methyl carbamate, t-amyl carbamate, S-benzyl thiocarbamate, p-cyanobenzyl carbamate, cyclobutyl carbamate, cyclohexyl carbamate, cyclopentyl carbamate, cyclopropylmethyl carbamate, p- decyloxybenzyl carbamate, 2,2-dimethoxyacylvinyl carbamate, o-(N,N- dimethylcarboxamido)benzyl carbamate, 1,1-dimethyl-3-(N,N-dimethylcarboxamido)propyl carbamate, 1,1-dimethylpropynyl carbamate, di(2-pyridyl)methyl carbamate, 2-furanylmethyl carbamate, 2-iodoethyl carbamate, isobornyl carbamate, isobutyl carbamate, isonicotinyl carbamate, p-(p’-methoxyphenylazo)benzyl carbamate, 1-methylcyclobutyl carbamate, 1- methylcyclohexyl carbamate, 1-methyl-1-cyclopropylmethyl carbamate, 1-methyl-1-(3,5- dimethoxyphenyl)ethyl carbamate, 1-methyl-1-(p-phenylazophenyl)ethyl carbamate, 1- methyl-1-phenylethyl carbamate, 1-methyl-1-(4-pyridyl)ethyl carbamate, phenyl carbamate, p-(phenylazo)benzyl carbamate, 2,4,6-tri-t-butylphenyl carbamate, 4- (trimethylammonium)benzyl carbamate, and 2,4,6-trimethylbenzyl carbamate. [0076] Nitrogen protecting groups such as sulfonamide groups (e.g., –S(=O) ₂ R ^aa ) include, but are not limited to, p-toluenesulfonamide (Ts), benzenesulfonamide, 2,3,6-trimethyl-4- methoxybenzenesulfonamide (Mtr), 2,4,6-trimethoxybenzenesulfonamide (Mtb), 2,6- dimethyl-4-methoxybenzenesulfonamide (Pme), 2,3,5,6-tetramethyl-4- methoxybenzenesulfonamide (Mte), 4-methoxybenzenesulfonamide (Mbs), 2,4,6- trimethylbenzenesulfonamide (Mts), 2,6-dimethoxy-4-methylbenzenesulfonamide (iMds), 2,2,5,7,8-pentamethylchroman-6-sulfonamide (Pmc), methanesulfonamide (Ms), β- trimethylsilylethanesulfonamide (SES), 9-anthracenesulfonamide, 4-(4’,8’- dimethoxynaphthylmethyl)benzenesulfonamide (DNMBS), benzylsulfonamide, trifluoromethylsulfonamide, and phenacylsulfonamide. Other nitrogen protecting groups include, but are not limited to, phenothiazinyl-(10)-acyl derivative, N’-p-toluenesulfonylaminoacyl derivative, N’-phenylaminothioacyl derivative, N- benzoylphenylalanyl derivative, N-acetylmethionine derivative, 4,5-diphenyl-3-oxazolin-2- one, N-phthalimide, N-dithiasuccinimide (Dts), N-2,3-diphenylmaleimide, N-2,5- dimethylpyrrole, N-1,1,4,4-tetramethyldisilylazacyclopentane adduct (STABASE), 5- substituted 1,3-dimethyl-1,3,5-triazacyclohexan-2-one, 5-substituted 1,3-dibenzyl-1,3,5- triazacyclohexan-2-one, 1-substituted 3,5-dinitro-4-pyridone, N-methylamine, N-allylamine, N-[2-(trimethylsilyl)ethoxy]methylamine (SEM), N-3-acetoxypropylamine, N-(1-isopropyl- 4-nitro-2-oxo-3-pyroolin-3-yl)amine, quaternary ammonium salts, N-benzylamine, N-di(4- methoxyphenyl)methylamine, N-5-dibenzosuberylamine, N-triphenylmethylamine (Tr), N- [(4-methoxyphenyl)diphenylmethyl]amine (MMTr), N-9-phenylfluorenylamine (PhF), N- 2,7-dichloro-9-fluorenylmethyleneamine, N-ferrocenylmethylamino (Fcm), N-2- picolylamino N’-oxide, N-1,1-dimethylthiomethyleneamine, N-benzylideneamine, N-p- methoxybenzylideneamine, N-diphenylmethyleneamine, N-[(2- pyridyl)mesityl]methyleneamine, N-(N’,N’-dimethylaminomethylene)amine, N,N’- isopropylidenediamine, N-p-nitrobenzylideneamine, N-salicylideneamine, N-5- chlorosalicylideneamine, N-(5-chloro-2-hydroxyphenyl)phenylmethyleneamine, N- cyclohexylideneamine, N-(5,5-dimethyl-3-oxo-1-cyclohexenyl)amine, N-borane derivative, N-diphenylborinic acid derivative, N-[phenyl(pentaacylchromium– or tungsten)acyl]amine, N-copper chelate, N-zinc chelate, N-nitroamine, N-nitrosoamine, amine N-oxide, diphenylphosphinamide (Dpp), dimethylthiophosphinamide (Mpt), diphenylthiophosphinamide (Ppt), dialkyl phosphoramidates, dibenzyl phosphoramidate, diphenyl phosphoramidate, benzenesulfenamide, o-nitrobenzenesulfenamide (Nps), 2,4- dinitrobenzenesulfenamide, pentachlorobenzenesulfenamide, 2-nitro-4- methoxybenzenesulfenamide, triphenylmethylsulfenamide, and 3-nitropyridinesulfenamide (Npys). [0077] In certain embodiments, the substituent present on an oxygen atom is an oxygen protecting group (also referred to herein as an “hydroxyl protecting group”). Oxygen protecting groups include, but are not limited to, –R ^aa , –N(R ^bb ) ₂ , –C(=O)SR ^aa , –C(=O)R ^aa , –CO ₂ R ^aa , –C(=O)N(R ^bb ) ₂ , –C(=NR ^bb )R ^aa , –C(=NR ^bb )OR ^aa , –C(=NR ^bb )N(R ^bb ) ₂ , –S(=O)R ^aa , –SO ₂ R ^aa , –Si(R ^aa ) ₃ , –P(R ^cc ) ₂ , –P(R ^cc ) ₃ ⁺ X-, –P(OR ^cc ) ₂ , –P(OR ^cc ) ₃ ⁺ X-, –P(=O)(R ^aa ) ₂ , –P(=O)(OR ^cc ) ₂ , and –P(=O)(N(R ^bb ) ₂ ) ₂ , wherein R ^aa , R ^bb , and R ^cc are as defined herein. Oxygen protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3 ^rd edition, John Wiley & Sons, 1999, incorporated herein by reference. [0078] Exemplary oxygen protecting groups include, but are not limited to, methyl, methoxymethyl (MOM), methylthiomethyl (MTM), t-butylthiomethyl, (phenyldimethylsilyl)methoxymethyl (SMOM), benzyloxymethyl (BOM), p- methoxybenzyloxymethyl (PMBM), (4-methoxyphenoxy)methyl (p-AOM), guaiacolmethyl (GUM), t-butoxymethyl, 4-pentenyloxymethyl (POM), siloxymethyl, 2- methoxyethoxymethyl (MEM), 2,2,2-trichloroethoxymethyl, bis(2-chloroethoxy)methyl, 2- (trimethylsilyl)ethoxymethyl (SEMOR), tetrahydropyranyl (THP), 3- bromotetrahydropyranyl, tetrahydrothiopyranyl, 1-methoxycyclohexyl, 4- methoxytetrahydropyranyl (MTHP), 4-methoxytetrahydrothiopyranyl, 4- methoxytetrahydrothiopyranyl S,S-dioxide, 1-[(2-chloro-4-methyl)phenyl]-4- methoxypiperidin-4-yl (CTMP), 1,4-dioxan-2-yl, tetrahydrofuranyl, tetrahydrothiofuranyl, 2,3,3a,4,5,6,7,7a-octahydro-7,8,8-trimethyl-4,7-methanobenzo furan-2-yl, 1-ethoxyethyl, 1- (2-chloroethoxy)ethyl, 1-methyl-1-methoxyethyl, 1-methyl-1-benzyloxyethyl, 1-methyl-1- benzyloxy-2-fluoroethyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, 2-(phenylselenyl)ethyl, t- butyl, allyl, p-chlorophenyl, p-methoxyphenyl, 2,4-dinitrophenyl, benzyl (Bn), p- methoxybenzyl, 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6- dichlorobenzyl, p-cyanobenzyl, p-phenylbenzyl, 2-picolyl, 4-picolyl, 3-methyl-2-picolyl N- oxido, diphenylmethyl, p,p’-dinitrobenzhydryl, 5-dibenzosuberyl, triphenylmethyl, α- naphthyldiphenylmethyl, p-methoxyphenyldiphenylmethyl, di(p- methoxyphenyl)phenylmethyl, tri(p-methoxyphenyl)methyl, 4-(4’- bromophenacyloxyphenyl)diphenylmethyl, 4,4',4Ǝ-tris(4,5- dichlorophthalimidophenyl)methyl, 4,4',4Ǝ-tris(levulinoyloxyphenyl)methyl, 4,4',4Ǝ- tris(benzoyloxyphenyl)methyl, 3-(imidazol-1-yl)bis(4',4Ǝ-dimethoxyphenyl)methyl, 1,1- bis(4-methoxyphenyl)-1'-pyrenylmethyl, 9-anthryl, 9-(9-phenyl)xanthenyl, 9-(9-phenyl-10- oxo)anthryl, 1,3-benzodithiolan-2-yl, benzisothiazolyl S,S-dioxido, trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), dimethylisopropylsilyl (IPDMS), diethylisopropylsilyl (DEIPS), dimethylthexylsilyl, t-butyldimethylsilyl (TBDMS), t- butyldiphenylsilyl (TBDPS), tribenzylsilyl, tri-p-xylylsilyl, triphenylsilyl, diphenylmethylsilyl (DPMS), t-butylmethoxyphenylsilyl (TBMPS), formate, benzoylformate, acetate, chloroacetate, dichloroacetate, trichloroacetate, trifluoroacetate, methoxyacetate, triphenylmethoxyacetate, phenoxyacetate, p-chlorophenoxyacetate, 3-phenylpropionate, 4- oxopentanoate (levulinate), 4,4-(ethylenedithio)pentanoate (levulinoyldithioacetal), pivaloate, adamantoate, crotonate, 4-methoxycrotonate, benzoate, p-phenylbenzoate, 2,4,6- trimethylbenzoate (mesitoate), methyl carbonate, 9-fluorenylmethyl carbonate (Fmoc), ethyl carbonate, 2,2,2-trichloroethyl carbonate (Troc), 2-(trimethylsilyl)ethyl carbonate (TMSEC), 2-(phenylsulfonyl) ethyl carbonate (Psec), 2-(triphenylphosphonio) ethyl carbonate (Peoc), isobutyl carbonate, vinyl carbonate, allyl carbonate, t-butyl carbonate (BOC or Boc), p- nitrophenyl carbonate, benzyl carbonate, p-methoxybenzyl carbonate, 3,4-dimethoxybenzyl carbonate, o-nitrobenzyl carbonate, p-nitrobenzyl carbonate, S-benzyl thiocarbonate, 4- ethoxy-1-napththyl carbonate, methyl dithiocarbonate, 2-iodobenzoate, 4-azidobutyrate, 4- nitro-4-methylpentanoate, o-(dibromomethyl)benzoate, 2-formylbenzenesulfonate, 2- (methylthiomethoxy)ethyl, 4-(methylthiomethoxy)butyrate, 2- (methylthiomethoxymethyl)benzoate, 2,6-dichloro-4-methylphenoxyacetate, 2,6-dichloro-4- (1,1,3,3-tetramethylbutyl)phenoxyacetate, 2,4-bis(1,1-dimethylpropyl)phenoxyacetate, chlorodiphenylacetate, isobutyrate, monosuccinoate, (E)-2-methyl-2-butenoate, o- (methoxyacyl)benzoate, α-naphthoate, nitrate, alkyl N,N,N’,N’- tetramethylphosphorodiamidate, alkyl N-phenylcarbamate, borate, dimethylphosphinothioyl, alkyl 2,4-dinitrophenylsulfenate, sulfate, methanesulfonate (mesylate), benzylsulfonate, and tosylate (Ts). [0079] In certain embodiments, the substituent present on a sulfur atom is a sulfur protecting group (also referred to as a “thiol protecting group”). Sulfur protecting groups include, but are not limited to, –R ^aa , –N(R ^bb ) ₂ , –C(=O)SR ^aa , –C(=O)R ^aa , –CO ₂ R ^aa , –C(=O)N(R ^bb ) ₂ , –C(=NR ^bb )R ^aa , –C(=NR ^bb )OR ^aa , –C(=NR ^bb )N(R ^bb ) ₂ , –S(=O)R ^aa , –SO ₂ R ^aa , –Si(R ^aa ) ₃ , –P(R ^cc ) ₂ , –P(R ^cc ) ₃ ⁺ X-, –P(OR ^cc ) ₂ , –P(OR ^cc ) ₃ ⁺ X-, –P(=O)(R ^aa ) ₂ , –P(=O)(OR ^cc ) ₂ , and –P(=O)(N(R ^bb ) ₂ ) ₂ , wherein R ^aa , R ^bb , and R ^cc are as defined herein. Sulfur protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3 ^rd edition, John Wiley & Sons, 1999, incorporated herein by reference. [0080] The term “leaving group” is given its ordinary meaning in the art of synthetic organic chemistry and refers to an atom or a group capable of being displaced by a nucleophile. Examples of suitable leaving groups include, but are not limited to, halogen (such as F, –Cl, –Br, or I (iodine)), alkoxycarbonyloxy, aryloxycarbonyloxy, alkanesulfonyloxy, arenesulfonyloxy, alkyl-carbonyloxy (e.g., acetoxy), arylcarbonyloxy, aryloxy, methoxy, N,O-dimethylhydroxylamino, pixyl, and haloformates. In certain embodiments, the leaving group is halogen, alkanesulfonyloxy, arenesulfonyloxy, diazonium, alkyl diazenes, aryl diazenes, alkyl triazenes, aryl triazenes, nitro, alkyl nitrate, aryl nitrate, alkyl phosphate, aryl phosphate, alkyl carbonyl oxy, aryl carbonyl oxy, alkoxcarbonyl oxy, aryoxcarbonyl oxy ammonia, alkyl amines, aryl amines, hydroxyl group, alkyloxy group, or aryloxy. In some cases, the leaving group is a sulfonic acid ester, such as toluenesulfonate (tosylate, –OTs), methanesulfonate (mesylate, –OMs), p-bromobenzenesulfonyloxy (brosylate, –OBs), –OS(=O) ₂ (CF ₂ ) ₃ CF ₃ (nonaflate, –ONf), or trifluoromethanesulfonate (triflate, –OTf). In some cases, the leaving group is a brosylate, such as p- bromobenzenesulfonyloxy. In some cases, the leaving group is a nosylate, such as 2- nitrobenzenesulfonyloxy. In some embodiments, the leaving group is a sulfonate-containing group. In some embodiments, the leaving group is a tosylate group. The leaving group may also be a phosphineoxide (e.g., formed during a Mitsunobu reaction) or an internal leaving group such as an epoxide or cyclic sulfate. Other non-limiting examples of leaving groups are water, ammonia, alcohols, ether moieties, thioether moieties, zinc halides, magnesium moieties, diazonium salts, and copper moieties. [0081] “Carboxy” refers to the radical –C(=O)OH. [0082] “Cyano” refers to the radical –CN. [0083] “Halo” or “halogen” refers to fluoro (F), chloro (Cl), bromo (Br), and iodo (I). In certain embodiments, the halo group is either fluoro or chloro. [0084] “Haloalkyl” refers to an alkyl radical in which the alkyl group is substituted with one or more halogens. Typical haloalkyl groups include, but are not limited to, trifluoromethyl (–CF ₃ ), difluoromethyl (–CHF ₂ ), fluoromethyl (–CH ₂ F), chloromethyl (– CH ₂ Cl), dichloromethyl (–CHCl ₂ ), tribromomethyl (–CH ₂ Br), and the like. [0085] “Hydroxy” refers to the radical –OH. [0086] “Nitro” refers to the radical –NO ₂ . [0087] “Thioketo” refers to the group =S. [0088] Alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups, as defined herein, are optionally substituted (e.g., “substituted” or “unsubstituted” alkyl, “substituted” or “unsubstituted” alkenyl, “substituted” or “unsubstituted” alkynyl, “substituted” or “unsubstituted” carbocyclyl, “substituted” or “unsubstituted” heterocyclyl, “substituted” or “unsubstituted” aryl or “substituted” or “unsubstituted” heteroaryl group). In general, the term “substituted”, whether preceded by the term “optionally” or not, means that at least one hydrogen present on a group (e.g., a carbon or nitrogen atom) is replaced with a permissible substituent, e.g., a substituent which upon substitution results in a stable compound, e.g., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction. Unless otherwise indicated, a “substituted” group has a substituent at one or more substitutable positions of the group, and when more than one position in any given structure is substituted, the substituent is either the same or different at each position. The term “substituted” is contemplated to include substitution with all permissible substituents of organic compounds, any of the substituents described herein that results in the formation of a stable compound. Any and all such combinations are contemplated in order to arrive at a stable compound. For purposes of this disclosure, heteroatoms such as nitrogen may have hydrogen substituents and/or any suitable substituent as described herein which satisfy the valencies of the heteroatoms and results in the formation of a stable moiety. [0089] Exemplary carbon atom substituents include, but are not limited to, halogen, –CN, – NO ₂ , –N ₃ , –SO ₂ H, –SO ₃ H, –OH, –OR ^aa , –ON(R ^bb ) ₂ , –N(R ^bb ) ₂ , –N(R ^bb ) ₃ ⁺ X ^– , –N(OR ^cc )R ^bb , – SH, –SR ^aa , –SSR ^cc , –C(=O)R ^aa , –CO ₂ H, –CHO, –C(OR ^cc ) ₂ , –CO ₂ R ^aa , –OC(=O)R ^aa , – OCO ₂ R ^aa , –C(=O)N(R ^bb ) ₂ , –OC(=O)N(R ^bb ) ₂ , –NR ^bb C(=O)R ^aa , –NR ^bb CO ₂ R ^aa , – NR ^bb C(=O)N(R ^bb ) ₂ , –C(=NR ^bb )R ^aa , –C(=NR ^bb )OR ^aa , –OC(=NR ^bb )R ^aa , –OC(=NR ^bb )OR ^aa , – C(=NR ^bb )N(R ^bb ) ₂ , –OC(=NR ^bb )N(R ^bb ) ₂ , –NR ^bb C(=NR ^bb )N(R ^bb ) ₂ , –C(=O)NR ^bb SO ₂ R ^aa , – NR ^bb SO ₂ R ^aa , –SO ₂ N(R ^bb ) ₂ , –SO ₂ R ^aa , –SO ₂ OR ^aa , –OSO ₂ R ^aa , –S(=O)R ^aa , –S(=O)(=NR ^bb )R ^aa , – OS(=O)R ^aa , –Si(R ^aa ) ₃ , –OSi(R ^aa ) ₃ –C(=S)N(R ^bb ) ₂ , –C(=O)SR ^aa , –C(=S)SR ^aa , –SC(=S)SR ^aa , – SC(=O)SR ^aa , –OC(=O)SR ^aa , –SC(=O)OR ^aa , –SC(=O)R ^aa , –P(=O) ₂ R ^aa , –OP(=O) ₂ R ^aa , – P(=O)(R ^aa ) ₂ , –OP(=O)(R ^aa ) ₂ , –OP(=O)(OR ^cc ) ₂ , –P(=O) ₂ N(R ^bb ) ₂ , –OP(=O) ₂ N(R ^bb ) ₂ , – P(=O)(NR ^bb ) ₂ , –OP(=O)(NR ^bb ) ₂ , –NR ^bb P(=O)(OR ^cc ) ₂ , –NR ^bb P(=O)(NR ^bb ) ₂ , –P(R ^cc ) ₂ , – P(R ^cc ) ₃ , –OP(R ^cc ) ₂ , –OP(R ^cc ) ₃ , –B(R ^aa ) ₂ , –B(OR ^cc ) ₂ , –BR ^aa (OR ^cc ), –C _1–10 alkyl, –C _1–10 haloalkyl, –C _2–10 alkenyl, –C _2–10 alkynyl, C _3–10 carbocyclyl, 3–14 membered heterocyclyl, C _{6– 14} aryl, and 5–14 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups; or two geminal hydrogens on a carbon atom are replaced with the group =O, =S, =NN(R ^bb ) ₂ , =NNR ^bb C(=O)R ^aa , =NNR ^bb C(=O)OR ^aa , =NNR ^bb S(=O) ₂ R ^aa , =NR ^bb , or =NOR ^cc ; each instance of R ^aa is, independently, selected from C _1–10 alkyl, –C _1–10 haloalkyl, –C _2–10 alkenyl, –C _2–10 alkynyl, C _3–10 carbocyclyl, 3–14 membered heterocyclyl, C6–14 aryl, and 5–14 membered heteroaryl, or two R ^aa groups are joined to form a 3–14 membered heterocyclyl or 5–14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups; each instance of R ^bb is, independently, selected from hydrogen, –OH, –OR ^aa , –N(R ^cc ) ₂ , –CN, –C(=O)R ^aa , –C(=O)N(R ^cc ) ₂ , –CO ₂ R ^aa , –SO ₂ R ^aa , –C(=NR ^cc )OR ^aa , –C(=NR ^cc )N(R ^cc ) ₂ , – SO ₂ N(R ^cc ) ₂ , –SO ₂ R ^cc , –SO ₂ OR ^cc , –SOR ^aa , –C(=S)N(R ^cc ) ₂ , –C(=O)SR ^cc , –C(=S)SR ^cc , – P(=O) ₂ R ^aa , –P(=O)(R ^aa ) ₂ , –P(=O) ₂ N(R ^cc ) ₂ , –P(=O)(NR ^cc ) ₂ , –C _1–10 alkyl, –C _1–10 haloalkyl, – C _2–10 alkenyl, –C _2–10 alkynyl, C _3–10 carbocyclyl, 3–14 membered heterocyclyl, C _6–14 aryl, and 5–14 membered heteroaryl, or two R ^bb groups are joined to form a 3–14 membered heterocyclyl or 5–14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups; each instance of R ^cc is, independently, selected from hydrogen, –C _1–10 alkyl, –C _1–10 haloalkyl, –C _2–10 alkenyl, –C _2–10 alkynyl, C _3–10 carbocyclyl, 3–14 membered heterocyclyl, C6–14 aryl, and 5–14 membered heteroaryl, or two R ^cc groups are joined to form a 3–14 membered heterocyclyl or 5–14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups; each instance of R ^dd is, independently, selected from halogen, –CN, –NO ₂ , –N ₃ , –SO ₂ H, – SO ₃ H, –OH, –OR ^ee , –ON(R ^ff ) ₂ , –N(R ^ff ) ₂ , –N(R ^ff ) ₃ ⁺ X ^– , –N(OR ^ee )R ^ff , –SH, –SR ^ee , –SSR ^ee , – C(=O)R ^ee , –CO ₂ H, –CO ₂ R ^ee , –OC(=O)R ^ee , –OCO ₂ R ^ee , –C(=O)N(R ^ff ) ₂ , –OC(=O)N(R ^ff ) ₂ , – NR ^ff C(=O)R ^ee , –NR ^ff CO ₂ R ^ee , –NR ^ff C(=O)N(R ^ff ) ₂ , –C(=NR ^ff )OR ^ee , –OC(=NR ^ff )R ^ee , – OC(=NR ^ff )OR ^ee , –C(=NR ^ff )N(R ^ff ) ₂ , –OC(=NR ^ff )N(R ^ff ) ₂ , –NR ^ff C(=NR ^ff )N(R ^ff ) ₂ ,–NR ^ff SO ₂ R ^ee , –SO ₂ N(R ^ff ) ₂ , –SO ₂ R ^ee , –SO ₂ OR ^ee , –OSO ₂ R ^ee , –S(=O)R ^ee , –Si(R ^ee ) ₃ , –OSi(R ^ee ) ₃ , – C(=S)N(R ^ff ) ₂ , –C(=O)SR ^ee , –C(=S)SR ^ee , –SC(=S)SR ^ee , –P(=O) ₂ R ^ee , –P(=O)(R ^ee ) ₂ , – OP(=O)(R ^ee ) ₂ , –OP(=O)(OR ^ee ) ₂ , –C _1–6 alkyl, –C _1–6 haloalkyl, –C _2–6 alkenyl, –C _2–6 alkynyl, C _3–10 carbocyclyl, 3–10 membered heterocyclyl, C _6–10 aryl, 5–10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^gg groups, or two geminal R ^dd substituents can be joined to form =O or =S; each instance of R ^ee is, independently, selected from C _1–6 alkyl, –C _1–6 haloalkyl, –C _2–6 alkenyl, –C _2–6 alkynyl, C _3–10 carbocyclyl, C _6–10 aryl, 3–10 membered heterocyclyl, and 3–10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^gg groups; each instance of R ^ff is, independently, selected from hydrogen, –C _1–6 alkyl, –C _1–6 haloalkyl, – C _2–6 alkenyl, –C _2–6 alkynyl, C _3–10 carbocyclyl, 3–10 membered heterocyclyl, C _6–10 aryl and 5– 10 membered heteroaryl, or two R ^ff groups are joined to form a 3–14 membered heterocyclyl or 5–14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^gg groups; and each instance of R ^gg is, independently, halogen, –CN, –NO ₂ , –N ₃ , –SO ₂ H, –SO ₃ H, –OH, – OC _1–6 alkyl, –ON(C _1–6 alkyl) ₂ , –N(C _1–6 alkyl) ₂ , –N(C _1–6 alkyl) ₃ ⁺ X ^– , –NH(C _1–6 alkyl) ₂ ⁺ X ^– , – NH ₂ (C _1–6 alkyl) ⁺ X ^– , –NH ₃ ⁺ X ^– , –N(OC _1–6 alkyl)(C _1–6 alkyl), –N(OH)(C _1–6 alkyl), –NH(OH), –SH, –SC _1–6 alkyl, –SS(C _1–6 alkyl), –C(=O)(C _1–6 alkyl), –CO ₂ H, –CO ₂ (C _1–6 alkyl), – OC(=O)(C _1–6 alkyl), –OCO ₂ (C _1–6 alkyl), –C(=O)NH ₂ , –C(=O)N(C _1–6 alkyl) ₂ , – OC(=O)NH(C _1–6 alkyl), –NHC(=O)(C _1–6 alkyl), –N(C _1–6 alkyl)C(=O)(C _1–6 alkyl), – NHCO ₂ (C _1–6 alkyl), –NHC(=O)N(C _1–6 alkyl) ₂ , –NHC(=O)NH(C _1–6 alkyl), –NHC(=O)NH ₂ , – C(=NH)O(C _1–6 alkyl),–OC(=NH)(C _1–6 alkyl), –OC(=NH)OC _1–6 alkyl, –C(=NH)N(C _1–6 alkyl) ₂ , –C(=NH)NH(C _1–6 alkyl), –C(=NH)NH ₂ , –OC(=NH)N(C _1–6 alkyl) ₂ , –OC(NH)NH(C1– 6 alkyl), –OC(NH)NH ₂ , –NHC(NH)N(C _1–6 alkyl) ₂ , –NHC(=NH)NH ₂ , –NHSO ₂ (C _1–6 alkyl), – SO ₂ N(C _1–6 alkyl) ₂ , –SO ₂ NH(C _1–6 alkyl), –SO ₂ NH ₂ ,–SO ₂ C _1–6 alkyl, –SO ₂ OC _1–6 alkyl, – OSO ₂ C _1–6 alkyl, –SOC _1–6 alkyl, –Si(C _1–6 alkyl) ₃ , –OSi(C _1–6 alkyl) ₃ –C(=S)N(C _1–6 alkyl) ₂ , – C(=S)NH(C _1–6 alkyl), –C(=S)NH ₂ , –C(=O)S(C _1–6 alkyl), –C(=S)SC _1–6 alkyl, –SC(=S)SC _1–6 alkyl, –P(=O) ₂ (C _1–6 alkyl), –P(=O)(C _1–6 alkyl) ₂ , –OP(=O)(C _1–6 alkyl) ₂ , –OP(=O)(OC _1–6 alkyl) ₂ , –C _1–6 alkyl, –C _1–6 haloalkyl, –C _2–6 alkenyl, –C _2–6 alkynyl, C _3–10 carbocyclyl, C _6–10 aryl, 3–10 membered heterocyclyl, 5–10 membered heteroaryl; or two geminal R ^gg substituents can be joined to form =O or =S; wherein X ^– is a counterion. [0090] A “counterion” or “anionic counterion” is a negatively charged group associated with a cationic quaternary amino group in order to maintain electronic neutrality. Exemplary counterions include halide ions (e.g., F ^– , Cl ^– , Br ^– , I ^– ), NO ₃ ^– , ClO ₄ ^– , OH ^– , H ₂ PO ₄ ^– , HSO ₄ ^– , SO ₄ ^-2 sulfonate ions (e.g., methansulfonate, trifluoromethanesulfonate, p–toluenesulfonate, benzenesulfonate, 10–camphor sulfonate, naphthalene–2–sulfonate, naphthalene–1–sulfonic acid–5–sulfonate, ethan–1–sulfonic acid–2–sulfonate, and the like), and carboxylate ions (e.g., acetate, ethanoate, propanoate, benzoate, glycerate, lactate, tartrate, glycolate, and the like). Nitrogen atoms can be substituted or unsubstituted as valency permits, and include primary, secondary, tertiary, and quarternary nitrogen atoms. Exemplary nitrogen atom substitutents include, but are not limited to, hydrogen, –OH, –OR ^aa , –N(R ^cc ) ₂ , –CN, –C(=O)R ^aa , – C(=O)N(R ^cc ) ₂ , –CO ₂ R ^aa , –SO ₂ R ^aa , –C(=NR ^bb )R ^aa , –C(=NR ^cc )OR ^aa , –C(=NR ^cc )N(R ^cc ) ₂ , – SO ₂ N(R ^cc ) ₂ , –SO ₂ R ^cc , –SO ₂ OR ^cc , –SOR ^aa , –C(=S)N(R ^cc ) ₂ , –C(=O)SR ^cc , –C(=S)SR ^cc , – P(=O) ₂ R ^aa , –P(=O)(R ^aa ) ₂ , –P(=O) ₂ N(R ^cc ) ₂ , –P(=O)(NR ^cc ) ₂ , –C _1–10 alkyl, –C _1–10 haloalkyl, – C _2–10 alkenyl, –C _2–10 alkynyl, C _3–10 carbocyclyl, 3–14 membered heterocyclyl, C6–14 aryl, and 5–14 membered heteroaryl, or two R ^cc groups attached to a nitrogen atom are joined to form a 3–14 membered heterocyclyl or 5–14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R ^dd groups, and wherein R ^aa , R ^bb , R ^cc and R ^dd are as defined above. These and other exemplary substituents are described in more detail in the Detailed Description, Examples, and Claims. The invention is not intended to be limited in any manner by the above exemplary listing of substituents. Other definitions [0091] As used herein, the term “salt” refers to any and all salts and encompasses pharmaceutically acceptable salts. [0092] The term “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berge et al., describes pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences (1977) 66:1–19. Pharmaceutically acceptable salts of the compounds of this disclosure include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2–hydroxy–ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2– naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3–phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p–toluenesulfonate, undecanoate, valerate salts, and the like. Pharmaceutically acceptable salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N ⁺ (C1–4alkyl) ₄ salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate. [0093] A “subject” to which administration is contemplated includes, but is not limited to, humans (i.e., a male or female of any age group, e.g., a pediatric subject (e.g., infant, child, adolescent) or adult subject (e.g., young adult, middle–aged adult or senior adult)) and/or a non-human animal, e.g., a mammal such as primates (e.g., cynomologus monkeys, rhesus monkeys), cattle, pigs, horses, sheep, goats, rodents, cats, and/or dogs. In certain embodiments, the subject is a human. In certain embodiments, the subject is a non-human animal. The terms “human,” “patient,” and “subject” are used interchangeably herein. [0094] Disease, disorder, and condition are used interchangeably herein. [0095] As used herein, and unless otherwise specified, the terms “treat,” “treating” and “treatment” contemplate an action that occurs while a subject is suffering from the specified disease, disorder or condition, which reduces the severity of the disease, disorder or condition, or retards or slows the progression of the disease, disorder or condition (“therapeutic treatment”), and also contemplates an action that occurs before a subject begins to suffer from the specified disease, disorder or condition (“prophylactic treatment”). In one embodiment, the compounds provided herein are contemplated to be used in methods of therapeutic treatment wherein the action occurs while a subject is suffering from the specified disease, disorder or condition and results in a reduction in the severity of the disease, disorder or condition, or retardation or slowing of the progression of the disease, disorder or condition. In an alternate embodiment, the compounds provided herein are contemplated to be used in methods of prophylactic treatment wherein the action occurs before a subject begins to suffer from the specified disease, disorder or condition and results in preventing a disease, disorder or condition, or one or more symptoms associated with the disease, disorder or condition, or preventing the recurrence of the disease, disorder or condition. [0096] In general, the “effective amount” of a compound refers to an amount sufficient to elicit the desired biological response e.g., to treat a disease or disorder described herein. As will be appreciated by those of ordinary skill in this art, the effective amount of a compound of the disclosure may vary depending on such factors as the desired biological endpoint, the pharmacokinetics of the compound, the disease being treated, the mode of administration, and the age, health, and condition of the subject. An effective amount encompasses therapeutic and prophylactic treatment (i.e., encompasses a “therapeutically effective amount” and a “prophylactically effective amount”). [0097] As used herein, and unless otherwise specified, a “therapeutically effective amount” of a compound is an amount sufficient to provide a therapeutic benefit in the therapeutic treatment of a disease, disorder or condition, or to delay or minimize one or more symptoms associated with the disease, disorder or condition. A therapeutically effective amount of a compound means an amount of therapeutic agent, alone or in combination with other therapies, which provides a therapeutic benefit in the therapeutic treatment of the disease, disorder or condition. The term “therapeutically effective amount” can encompass an amount that improves overall therapy, reduces or avoids symptoms or causes of disease or condition, or enhances the therapeutic efficacy of another therapeutic agent. [0098] As used herein, and unless otherwise specified, a “prophylactically effective amount” of a compound is an amount sufficient to prevent a disease, disorder or condition, or one or more symptoms associated with the disease, disorder or condition, or prevent its recurrence. A prophylactically effective amount of a compound means an amount of a therapeutic agent, alone or in combination with other agents, which provides a prophylactic benefit in the prevention of the disease, disorder or condition. The term “prophylactically effective amount” can encompass an amount that improves overall prophylaxis or enhances the prophylactic efficacy of another prophylactic agent. Compounds [0099] Provided herein are compounds of Formula (I) and Formula (A). Unless the context requires otherwise, reference throughout this specification to “a compound of Formula (I) or Formula (A)” or “compounds of Formula (I) or Formula (A)” refers to all embodiments of Formula (I) and Formula (A), including, for example, compounds of Formula (A), Formula (I), Formula (Ia), Formula (Ib), Formula (Ic), Formula (Id), Formula (II1), Formula (II1a), Formula (II2), Formula (II2a), Formula (II2b), Formula (II2c), Formula (II2d), Formula (II2e), Formula (II3), Formula (II3a), Formula (II3b), Formula (II3c), Formula (II3d), Formula (II3e), Formula (II3f), Formula (II3g), Formula (II3h), Formula (II4), Formula (II4a), Formula (II4b), Formula (II4c), Formula (II5), Formula (II5a), Formula (II6), Formula (II6a), Formula (II7), Formula (II7a), Formula (II7b), Formula (II7c), Formula (II7d), Formula (II8), Formula (II8a), Formula (II9), Formula (II9a), Formula (II10), Formula (II10a), Formula (II10b), Formula (II10c), Formula (II11), Formula (II11a), Formula (II11b), Formula (II11c), Formula (II11d), Formula (II11e), Formula (II12), Formula (II12a), Formula (II12b), Formula (II12c), Formula (III1), Formula (III1a), Formula (III1b), Formula (III1c), Formula (III1d),Formula (III2), Formula (III2a), Formula (III2b), Formula (III3), Formula (III3a), Formula (III3b), Formula (III4), Formula (III4a), Formula (III4b), Formula (III4c), Formula (III5), Formula (III5a), Formula (III5b), Formula (III6), Formula (III6a), Formula (III7), Formula (III7a), (i.e., Formula (I)-Formula (III7a)) as well as the compounds of Table 1. [0100] In one embodiment, provided herein are compounds of Formula (I) and Formula (A) or pharmaceutically acceptable salts thereof, wherein: Ring A is an optionally substituted fused bicyclic 8-10 membered heteroaryl ring system containing at least one nitrogen atom, wherein the 8-10 membered refers to the total number of atoms in the fused system; R ^B is an optionally substituted C ₁ -C ₆ alkyl; Ring B is selected from the group consisting of –C ₃ –C ₁₀ carbocyclyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, wherein each carbocyclyl, heterocyclyl, aryl and heteroaryl is optionally substituted at any available position; each R ¹ is independently absent or selected from the group consisting of H, –D, halo, –CN, – C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, 5-6-membered monocyclic heteroaryl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a1 , –N(R ^a1 ) ₂ , –C(=O)R ^a1 , –C(=O)OR ^a1 , –NR ^a1 C(=O)R ^a1 , – NR ^a1 C(=O)OR ^a1 , –C(=O)N(R ^a1 ) ₂ , –OC(=O)N(R ^a1 ) ₂ , –S(=O)R ^a1 , –S(=O) ₂ R ^a1 , –SR ^a1 , – S(=O)(=NR ^a1 )R ^a1 , –NR ^a1 S(=O) ₂ R ^a1 and –S(=O) ₂ N(R ^a1 ) ₂ ; each R ² is independently selected from the group consisting of –D, =O, halo, –CN, – C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a2 , –N(R ^a2 ) ₂ , –C(=O)R ^a2 , –C(=O)OR ^a2 , –NR ^a2 C(=O)R ^a2 , –NR ^a2 C(=O)OR ^a2 , –CH ₂ C(=O)N(R ^a2 ) ₂ – C(=O)N(R ^a2 ) ₂ , –OC(=O)N(R ^a2 ) ₂ , –CH ₂ C(=O)N(R ^a2 ) ₂ , –S(=O)R ^a2 , –S(=O) ₂ R ^a2 , –SR ^a2 , – S(=O)(=NR ^a2 )R ^a2 , –NR ^a2 S(=O) ₂ R ^a2 and –S(=O) ₂ N(R ^a2 ) ₂ or two instances of R ² together with the atom or atoms to which they are attached can be taken together to form a 3-10 membered cycloalkyl or heterocyclyl ring (e.g., a ring that together with the piperidine ring of Formula (I) or Formula (A) can form a bridged, fused or spiro bicyclic heterocyclic ring); each R ^a1 and R ^a2 is independently selected from the group consisting of H, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, C6-C ₁₀ aryl, 5-10 membered heteroaryl, arylalkyl and heteroarylalkyl wherein each alkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is independently selected from the group consisting of =O, halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, – OR ^b , –N(R ^b ) ₂ , –C(=O)R ^b , –C(=O)OR ^b , –NR ^b C(=O)R ^b , –NR ^b C(=O)OR ^b , –C(=O)N(R ^b ) ₂ , – OC(=O)N(R ^b ) ₂ , –S(=O)R ^b , –S(=O) ₂ R ^b , –SR ^b , –S(=O)(=NR ^b )R ^b , –NR ^b S(=O) ₂ R ^b and – S(=O) ₂ N(R ^b ) ₂ , wherein each R ^b is independently selected from the group consisting of H, – C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu)), and C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl); and n is 0, 1, 2 or 3; provided that: (i) when the compound is of Formula (A), Ring A is a 3-pyridine fused with a 5-membered heteroaryl via 2 carbon atoms; and (ii) the compound is not one of compounds a. to d. or a pharmaceutically acceptable salt thereof: a. N-(8-fluoroquinolin-3-yl)-2-oxo-2-(2-phenylpiperidin-1-yl)ac etamide b. 2-(2-(1H-pyrazol-4-yl)piperidin-1-yl)-N-(1H-indol-4-yl)-2-ox oacetamide c. 2-(2-(4-bromophenyl)piperidin-1-yl)-2-oxo-N-(pyrazolo[1,5-a] pyrimidin-3- yl)acetamide d. 2-(2-(1H-pyrazol-4-yl)piperidin-1-yl)-N-(1H-indazol-5-yl)-2- oxoacetamide [0101] In one embodiment, provided herein are compounds of Formula (I) and Formula (A) or pharmaceutically acceptable salts thereof, wherein:

Ring A is a fused bicyclic 8-10 membered heteroaryl ring system containing at least one nitrogen atom, wherein the 8-10 membered refers to the total number of atoms in the fused system, substituted at any available positions with 0, 1, 2 or 3 instances of R ⁴ ; R ^B is C ₁ -C ₆ alkyl substituted with 0, 1, 2 or 3 substituents independently selected from =O, –F, –Cl, –OH–, –OMe, –NH ₂ and –CN; Ring B is selected from the group consisting of –C ₃ –C ₁₀ carbocyclyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, wherein each carbocyclyl, heterocyclyl, aryl and heteroaryl is substituted at any available position with 0, 1, 2 or 3 instances of R ³ ; each R ¹ is independently absent or selected from the group consisting of H, –D, halo, – CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, 5-6-membered monocyclic heteroaryl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a1 , –N(R ^a1 ) ₂ , –C(=O)R ^a1 , –C(=O)OR ^a1 , –NR ^a1 C(=O)R ^a1 , – NR ^a1 C(=O)OR ^a1 , –C(=O)N(R ^a1 ) ₂ , –OC(=O)N(R ^a1 ) ₂ , –S(=O)R ^a1 , –S(=O) ₂ R ^a1 , –SR ^a1 , – S(=O)(=NR ^a1 )R ^a1 , –NR ^a1 S(=O) ₂ R ^a1 and –S(=O) ₂ N(R ^a1 ) ₂ ; each R ² is independently selected from the group consisting of –D, =O, halo, –CN, – C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a2 , –N(R ^a2 ) ₂ , –C(=O)R ^a2 , –C(=O)OR ^a2 , –NR ^a2 C(=O)R ^a2 , –NR ^a2 C(=O)OR ^a2 , –CH ₂ C(=O)N(R ^a2 ) ₂ – C(=O)N(R ^a2 ) ₂ , –OC(=O)N(R ^a2 ) ₂ , –CH ₂ C(=O)N(R ^a2 ) ₂ , –S(=O)R ^a2 , –S(=O) ₂ R ^a2 , –SR ^a2 , – S(=O)(=NR ^a2 )R ^a2 , –NR ^a2 S(=O) ₂ R ^a2 and –S(=O) ₂ N(R ^a2 ) ₂ or two instances of R ² together with the atom or atoms to which they are attached can be taken together to form a 3-10 membered cycloalkyl or heterocyclyl ring (e.g., a ring that together with the piperidine ring of Formula (I) or Formula (A) can form a bridged, fused or spiro bicyclic heterocyclic ring); each R ^a1 and R ^a2 is independently selected from the group consisting of H, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, C6-C ₁₀ aryl, 5-10 membered heteroaryl, arylalkyl and heteroarylalkyl wherein each alkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is independently selected from the group consisting of =O, halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, – OR ^b , –N(R ^b ) ₂ , –C(=O)R ^b , –C(=O)OR ^b , –NR ^b C(=O)R ^b , –NR ^b C(=O)OR ^b , –C(=O)N(R ^b ) ₂ , – OC(=O)N(R ^b ) ₂ , –S(=O)R ^b , –S(=O) ₂ R ^b , –SR ^b , –S(=O)(=NR ^b )R ^b , –NR ^b S(=O) ₂ R ^b and – S(=O) ₂ N(R ^b ) ₂ , wherein each R ^b is independently selected from the group consisting of H, – C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu)), and C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl); each R ³ is independently selected from the group consisting of –D, =O, –CN, halo, – C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, –OR ^a3 , –N(R ^a3 ) ₂ , –C(=O)R ^a3 , –C(=O)OR ^a3 , –NR ^a3 C(=O)R ^a3 , – NR ^a3 C(=O)OR ^a3 , –C(=O)N(R ^a3 ) ₂ , –OC(=O)R ^a3 , –OC(=O)N(R ^a3 ) ₂ , –S(=O)R ^a3 , –S(=O) ₂ R ^a3 , – SR ^a3 , –S(=O)(=NR ^a3 )R ^a3 , –NR ^a3 S(=O) ₂ R ^a3 and –S(=O) ₂ N(R ^a3 ) ₂ , wherein each alkyl, cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl and heteroarylalkyl of R ³ is optionally substituted at any available position (e.g., substituted with 0, 1, 2, 3, 4, or 5 instances of R ⁶ , wherein each R ⁶ is independently selected from the group consisting of –C ₁ –C ₆ alkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, –OH, =O, halo, –OC ₁ -C ₆ alkyl, –C ₁ –C ₆ haloalkyl, –C(=O)C ₁ -C ₆ alkyl, –N(C ₁ -C ₆ alkyl) ₂ , – C ₁ –C ₆ heteroalkyl, and –NHC(=O)C ₁ -C ₆ alkyl, wherein one or more hydrogens of the –C ₁ – C ₆ alkyl can be replaced with deuterium); and each R ^a3 is independently selected from the group consisting of H, –C ₁ –C ₆ alkyl, –C ₁ – C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, C6-C ₁₀ aryl, 5-10 membered heteroaryl, arylalkyl and heteroarylalkyl wherein each alkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is independently selected from the group consisting of =O, halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, – OR ^b , –N(R ^b ) ₂ , –C(=O)R ^b , –C(=O)OR ^b , –NR ^b C(=O)R ^b , –NR ^b C(=O)OR ^b , –C(=O)N(R ^b ) ₂ , – OC(=O)N(R ^b ) ₂ , –S(=O)R ^b , –S(=O) ₂ R ^b , –SR ^b , –S(=O)(=NR ^b )R ^b , –NR ^b S(=O) ₂ R ^b and – S(=O) ₂ N(R ^b ) ₂ , wherein each R ^b is independently selected from the group consisting of H, – C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu)), and C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl). each R ⁴ is independently selected from the group consisting of –D, halo, =O, –CN, – C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a4 , –N(R ^a4 ) ₂ , –C(=O)R ^a4 , –C(=O)OR ^a4 , –NR ^a4 C(=O)R ^a4 , –NR ^a4 C(=O)OR ^a4 , –C(=O)N(R ^a4 ) ₂ , – C(=O)N(OR ^a4 )(R ^a4 ), –OC(=O)N(R ^a4 ) ₂ , –S(=O)R ^a4 , –S(=O) ₂ R ^a4 , –SR ^a4 , –S(=O)(=NR ^a4 )R ^a4 , – NR ^a4 S(=O) ₂ R ^a4 and –S(=O) ₂ N(R ^a4 ) ₂ ; and each R ^a4 is independently selected from the group consisting of H, –C ₁ –C ₆ alkyl, –C1– C6 heteroalkyl, –C ₁ –C ₆ haloalkyl, C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, C6-C ₁₀ aryl, 5-10 membered heteroaryl, arylalkyl and heteroarylalkyl wherein each alkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is independently selected from the group consisting of =O, halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, – OR ^b , –N(R ^b ) ₂ , –C(=O)R ^b , –C(=O)OR ^b , –NR ^b C(=O)R ^b , –NR ^b C(=O)OR ^b , –C(=O)N(R ^b ) ₂ , – OC(=O)N(R ^b ) ₂ , –S(=O)R ^b , –S(=O) ₂ R ^b , –SR ^b , –S(=O)(=NR ^b )R ^b , –NR ^b S(=O) ₂ R ^b and – S(=O) ₂ N(R ^b ) ₂ , wherein each R ^b is independently selected from the group consisting of H, – C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu)), and C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl); and n is 0, 1, 2 or 3; provided that: (i) when the compound is of Formula (A), Ring A is a 3-pyridine fused with a 5-membered heteroaryl via 2 carbon atoms; and (ii) the compound is not one of compounds a. to d. or a pharmaceutically acceptable salt thereof: a. N-(8-fluoroquinolin-3-yl)-2-oxo-2-(2-phenylpiperidin-l-yl)ac etamide b. 2-(2-(lH-pyrazol-4-yl)piperidin-l-yl)-N-(lH-indol-4-yl)-2 -oxoacetamide c. 2-(2-(4-bromophenyl)piperidin-l-yl)-2-oxo-N-(pyrazolo[l,5-a] pyrimidin-3- yl)acetamide d. 2-(2-(lH-pyrazol-4-yl)piperidin-l-yl)-N-(lH-indazol-5-yl)-2- oxoacetamide

[0102] In some embodiments, the compound is of Formula (A). In some embodiments, the compound is of Formula (I) .

[0103] In some embodiments, provided herein are compounds of Formula (I): or a pharmaceutically acceptable salt thereof, wherein: Ring A is an optionally substituted fused bicyclic 8-10 membered heteroaryl ring system containing at least one nitrogen atom, wherein the 8-10 membered refers to the total number of atoms in the fused system; Ring B is selected from the group consisting of –C ₃ –C ₁₀ carbocyclyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, wherein each carbocyclyl, heterocyclyl, aryl and heteroaryl is optionally substituted at any available position; each R ¹ is independently absent or selected from the group consisting of H, –D, halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, 5-6-membered monocyclic heteroaryl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a1 , –N(R ^a1 ) ₂ , –C(=O)R ^a1 , –C(=O)OR ^a1 , – NR ^a1 C(=O)R ^a1 , –NR ^a1 C(=O)OR ^a1 , –C(=O)N(R ^a1 ) ₂ , –OC(=O)N(R ^a1 ) ₂ , –S(=O)R ^a1 , – S(=O) ₂ R ^a1 , –SR ^a1 , –S(=O)(=NR ^a1 )R ^a1 , –NR ^a1 S(=O) ₂ R ^a1 and –S(=O) ₂ N(R ^a1 ) ₂ ; each R ² is independently selected from the group consisting of –D, =O, halo, –CN, – C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a2 , –N(R ^a2 ) ₂ , –C(=O)R ^a2 , –C(=O)OR ^a2 , –NR ^a2 C(=O)R ^a2 , –NR ^a2 C(=O)OR ^a2 , –CH ₂ C(=O)N(R ^a2 ) ₂ – C(=O)N(R ^a2 ) ₂ , –OC(=O)N(R ^a2 ) ₂ , –CH ₂ C(=O)N(R ^a2 ) ₂ , –S(=O)R ^a2 , –S(=O) ₂ R ^a2 , –SR ^a2 , – S(=O)(=NR ^a2 )R ^a2 , –NR ^a2 S(=O) ₂ R ^a2 and –S(=O) ₂ N(R ^a2 ) ₂ or two instances of R ² together with the atom or atoms to which they are attached can be taken together to form a 3-10 membered cycloalkyl or heterocyclyl ring (e.g., a ring that together with the piperidine ring of Formula (I) or Formula (A) can form a bridged, fused or spiro bicyclic heterocyclic ring); each R ^a1 and R ^a2 is independently selected from the group consisting of H, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, C ₆ -C ₁₀ aryl, 5-10 membered heteroaryl, arylalkyl and heteroarylalkyl wherein each alkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is independently selected from the group consisting of =O, halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, – OR ^b , –N(R ^b ) ₂ , –C(=O)R ^b , –C(=O)OR ^b , –NR ^b C(=O)R ^b , –NR ^b C(=O)OR ^b , –C(=O)N(R ^b ) ₂ , – OC(=O)N(R ^b ) ₂ , –S(=O)R ^b , –S(=O) ₂ R ^b , –SR ^b , –S(=O)(=NR ^b )R ^b , –NR ^b S(=O) ₂ R ^b and – S(=O) ₂ N(R ^b ) ₂ , wherein each R ^b is independently selected from the group consisting of H, – C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu)), and C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl); and n is 0, 1, 2 or 3; provided that the compound is not one of compounds a. to d. or a pharmaceutically acceptable salt thereof: a. N-(8-fluoroquinolin-3-yl)-2-oxo-2-(2-phenylpiperidin-1-yl)ac etamide b. 2-(2-(1H-pyrazol-4-yl)piperidin-1-yl)-N-(1H-indol-4-yl)-2-ox oacetamide c. 2-(2-(4-bromophenyl)piperidin-1-yl)-2-oxo-N-(pyrazolo[1,5-a] pyrimidin-3- yl)acetamide d. 2-(2-(1H-pyrazol-4-yl)piperidin-1-yl)-N-(1H-indazol-5-yl)-2- oxoacetamide [0104] In one embodiment, provided herein are compounds of Formula (I): or pharmaceutically acceptable salts thereof, wherein: Ring A is an optionally substituted fused bicyclic 8-10 membered heteroaryl ring system containing at least one nitrogen atom, wherein the 8-10 membered refers to the total number of atoms in the fused system; Ring B is selected from the group consisting of –C ₃ –C ₁₀ carbocyclyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, wherein each carbocyclyl, heterocyclyl, aryl and heteroaryl is optionally substituted at any available position; each R ¹ is independently absent or selected from the group consisting of H, –D, halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, 5-6-membered monocyclic heteroaryl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a1 , –N(R ^a1 ) ₂ , –C(=O)R ^a1 , –C(=O)OR ^a1 , – NR ^a1 C(=O)R ^a1 , –NR ^a1 C(=O)OR ^a1 , –C(=O)N(R ^a1 ) ₂ , –OC(=O)N(R ^a1 ) ₂ , –S(=O)R ^a1 , – S(=O) ₂ R ^a1 , –SR ^a1 , –S(=O)(=NR ^a1 )R ^a1 , –NR ^a1 S(=O) ₂ R ^a1 and –S(=O) ₂ N(R ^a1 ) ₂ ; each R ² is independently selected from the group consisting of –D, =O, halo, –CN, – C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a2 , –N(R ^a2 ) ₂ , –C(=O)R ^a2 , –C(=O)OR ^a2 , –NR ^a2 C(=O)R ^a2 , –NR ^a2 C(=O)OR ^a2 , –CH ₂ C(=O)N(R ^a2 ) ₂ – C(=O)N(R ^a2 ) ₂ , –OC(=O)N(R ^a2 ) ₂ , –CH ₂ C(=O)N(R ^a2 ) ₂ , –S(=O)R ^a2 , –S(=O) ₂ R ^a2 , –SR ^a2 , – S(=O)(=NR ^a2 )R ^a2 , –NR ^a2 S(=O) ₂ R ^a2 and –S(=O) ₂ N(R ^a2 ) ₂ or two instances of R ² together with the atom or atoms to which they are attached can be taken together to form a 3-10 membered cycloalkyl or heterocyclyl ring (e.g., a ring that together with the piperidine ring of Formula (I) or Formula (A) can form a bridged, fused or spiro bicyclic heterocyclic ring); each R ^a1 and R ^a2 is independently selected from the group consisting of H, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ haloalkyl, –C ₁ –C ₆ heteroalkyl, C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, C6-C ₁₀ aryl, 5-10 membered heteroaryl, arylalkyl and heteroarylalkyl wherein each alkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is independently selected from the group consisting of =O, halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, –OR ^b , –N(R ^b ) ₂ , –C(=O)R ^b , –C(=O)OR ^b , –NR ^b C(=O)R ^b , –NR ^b C(=O)OR ^b , – C(=O)N(R ^b ) ₂ , –OC(=O)N(R ^b ) ₂ , –S(=O)R ^b , –S(=O) ₂ R ^b , –SR ^b , –S(=O)(=NR ^b )R ^b , – NR ^b S(=O) ₂ R ^b and –S(=O) ₂ N(R ^b ) ₂ , wherein each R ^b is independently selected from the group consisting of H, –C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu)), and C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl); and n is 0, 1, 2 or 3; provided that the compound is not: a. N-(8-fluoroquinolin-3-yl)-2-oxo-2-(2-phenylpiperidin-1-yl)ac etamide; b. 2-(2-(1H-pyrazol-4-yl)piperidin-1-yl)-N-(1H-indol-4-yl)-2-ox oacetamide; c. 2-(4-methyl-2-(5-methylfuran-2-yl)piperidin-1-yl)-2-oxo-N-(4 ,5,6,7-tetrahydro-1H- indazol-7-yl)acetamide; d. 2-(2-(1H-pyrazol-4-yl)piperidin-1-yl)-N-(1H-indazol-5-yl)-2- oxoacetamide. [0105] In one embodiment, provided is a compound of Formula (I) and Formula (A): or a pharmaceutically acceptable salt thereof, wherein: Ring A is a fused bicyclic 8-10 membered heteroaryl ring containing at least one nitrogen atom substituted at any available positions with 0, 1, 2 or 3 instances of R ⁴ , wherein the 8-10 membered refers to the total number of atoms in the fused system; Ring B is selected from the group consisting of –C ₃ –C ₁₀ carbocyclyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl and 5-10 membered heteroaryl, wherein each carbocyclyl, heterocyclyl, aryl and heteroaryl is substituted at any available position with 0, 1, 2 or 3 instances of R ³ ; each R ¹ is independently absent or selected from the group consisting of H, –D, halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, 5-6-membered monocyclic heteroaryl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a1 , –N(R ^a1 ) ₂ , –C(=O)R ^a1 , –C(=O)OR ^a1 , – NR ^a1 C(=O)R ^a1 , –NR ^a1 C(=O)OR ^a1 , –C(=O)N(R ^a1 ) ₂ , –OC(=O)N(R ^a1 ) ₂ , –S(=O)R ^a1 , – S(=O) ₂ R ^a1 , –SR ^a1 , –S(=O)(=NR ^a1 )R ^a1 , –NR ^a1 S(=O) ₂ R ^a1 and –S(=O) ₂ N(R ^a1 ) ₂ ; each R ² is independently selected from the group consisting of –D, =O, halo, –CN, – C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a2 , –N(R ^a2 ) ₂ , –C(=O)R ^a2 , –C(=O)OR ^a2 , –NR ^a2 C(=O)R ^a2 , –NR ^a2 C(=O)OR ^a2 , –CH ₂ C(=O)N(R ^a2 ) ₂ – C(=O)N(R ^a2 ) ₂ , –OC(=O)N(R ^a2 ) ₂ , –CH ₂ C(=O)N(R ^a2 ) ₂ , –S(=O)R ^a2 , –S(=O) ₂ R ^a2 , –SR ^a2 , – S(=O)(=NR ^a2 )R ^a2 , –NR ^a2 S(=O) ₂ R ^a2 and –S(=O) ₂ N(R ^a2 ) ₂ or two instances of R ² together with the atom or atoms to which they are attached can be taken together to form a 3-10 membered cycloalkyl or heterocyclyl ring (e.g., a ring that together with the piperidine ring of Formula (I) or Formula (A) can form a bridged, fused or spiro bicyclic heterocyclic ring); each R ³ is independently selected from the group consisting of –D, =O, –CN, halo, – C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, –OR ^a3 , –N(R ^a3 ) ₂ , –C(=O)R ^a3 , –C(=O)OR ^a3 , –NR ^a3 C(=O)R ^a3 , – NR ^a3 C(=O)OR ^a3 , –C(=O)N(R ^a3 ) ₂ , –OC(=O)R ^a3 , –OC(=O)N(R ^a3 ) ₂ , –S(=O)R ^a3 _, –S(=O) ₂ R ^a3 , – SR ^a3 , –S(=O)(=NR ^a3 )R ^a3 , –NR ^a3 S(=O) ₂ R ^a3 and –S(=O) ₂ N(R ^a3 ) ₂ , wherein each alkyl, cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl and heteroarylalkyl of R ³ is substituted at any available position with 0, 1, 2, 3, 4, or 5 instances of R ⁶ ; each R ⁴ is independently selected from the group consisting of halo, =O, –CN, – C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a4 , –N(R ^a4 ) ₂ , –C(=O)R ^a4 , –C(=O)OR ^a4 , –NR ^a4 C(=O)R ^a4 , –NR ^a4 C(=O)OR ^a4 , –C(=O)N(R ^a4 ) ₂ , – C(=O)N(OR ^a4 )(R ^a4 ), –OC(=O)N(R ^a4 ) ₂ , –S(=O)R ^a4 , –S(=O) ₂ R ^a4 , –SR ^a4 , –S(=O)(=NR ^a4 )R ^a4 , – NR ^a4 S(=O) ₂ R ^a4 and –S(=O) ₂ N(R ^a4 ) ₂ ; each R ⁶ is independently selected from the group consisting of –C ₁ –C ₆ alkyl, –C ₃ – C ₉ cycloalkyl, 3-10 membered heterocyclyl, –OH, =O, halo, –OC ₁ -C ₆ alkyl, –C ₁ –C ₆ haloalkyl, –C(=O)C ₁ -C ₆ alkyl, –N(C ₁ -C ₆ alkyl) ₂ , –C ₁ –C ₆ heteroalkyl, and –NHC(=O)C ₁ -C ₆ alkyl, wherein one or more hydrogens of the –C ₁ –C ₆ alkyl can be replaced with deuterium; each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently selected from the group consisting of H, – C ₁ –C ₆ alkyl, –C ₁ –C ₆ haloalkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, C ₃ –C ₉ cycloalkyl, 3- 10 membered heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, C ₆ -C ₁₀ aryl, 5-10 membered heteroaryl, arylalkyl and heteroarylalkyl wherein each alkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is substituted at any available position with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is independently selected from the group consisting of =O, halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, – OR ^b , –N(R ^b ) ₂ , –C(=O)R ^b , –C(=O)OR ^b , –NR ^b C(=O)R ^b , –NR ^b C(=O)OR ^b , –C(=O)N(R ^b ) ₂ , – OC(=O)N(R ^b ) ₂ , –S(=O)R ^b , –S(=O) ₂ R ^b , –SR ^b , –S(=O)(=NR ^b )R ^b , –NR ^b S(=O) ₂ R ^b and – ^S(=O) ₂ ^N(Rb) ₂ ^{, wherein each Rb is independently selected from the group consisting of H, –} C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu)), and C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl); and n is 0, 1, 2 or 3; provided that the compound is not: a. N-(8-fluoroquinolin-3-yl)-2-oxo-2-(2-phenylpiperidin-1-yl)ac etamide; b. 2-(2-(1H-pyrazol-4-yl)piperidin-1-yl)-N-(1H-indol-4-yl)-2-ox oacetamide; c. 2-(4-methyl-2-(5-methylfuran-2-yl)piperidin-1-yl)-2-oxo-N-(4 ,5,6,7-tetrahydro-1H- indazol-7-yl)acetamide; or d. 2-(2-(1H-pyrazol-4-yl)piperidin-1-yl)-N-(1H-indazol-5-yl)-2- oxoacetamide. [0106] As generally defined herein, R ^B is optionally substituted C ₁ -C ₆ alkyl. In some embodiments, R ^B is –C ₁ -C ₆ alkyl substituted with 0, 1, 2 or 3 substituents independently selected from =O, –F, –Cl, –OH–, –OMe, –NH ₂ and –CN. In some embodiments, R ^B is unsubstituted –C ₁ -C ₆ alkyl. In some embodiments, R ^B is selected from –Me, –Et–, –Pr, – ⁱ Pr and – ^t Bu. In some embodiments, R ^B is selected from –Me, –Et–, – ⁱ Pr and – ^t Bu. In some embodiments, R ¹ is not H and R ^B and R ¹ are in a trans relative configuration. In some embodiments, R ¹ is not H and R ^B and R ¹ are in a cis relative configuration. [0107] In some embodiments, R ¹ is absent (e.g., if a spiro ring formed by two R ² groups is attached to the atom that would otherwise bear R ¹ ). [0108] In certain embodiments, R ¹ is not H and Ring B and R ¹ are in a trans relative configuration. In other embodiments, R ¹ is not H and Ring B and R ¹ are in a cis relative configuration. [0109] In some embodiments, the moiety represented as in Formula (I) is selected from the group consisting of: wherein Ring B, R ¹ , R ² and n are as defined in any of the embodiments described herein. [0110] In certain embodiments, the moiety represented as is selected from the group consisting of: wherein Ring B, R ¹ , R ² and n are as defined in any of the embodiments described herein. [0111] In other embodiments, the moiety represented as is selected from the group consisting of: whe ^{1 2} rein Ring B, R , R and n are as defined in any of the embodiments described herein. [0112] In some embodiments, the compound of Formula (I) is of Formula (Ia) wherein Ring A, Ring B, R ¹ , R ² and n are as defined in any of the embodiments described herein. [0113] In some embodiments, the compound of Formula (I) is of Formula (Ib) wherein Ring A, Ring B, R ¹ , R ² and n are as defined in any of the embodiments described herein.

[0114] In some embodiments, the compound of Formula (I) is of Formula (Ic) wherein Ring A, Ring B, R ¹ , R ² and n are as defined in any of the embodiments described herein.

[0115] In some embodiments, the compound of Formula (I) is of Formula (Id) wherein Ring A, Ring B, R ¹ , R ² and n are as defined in any of the embodiments described herein.

[0116] As generally defined herein, Ring A is an optionally substituted fused bicyclic 8-10 membered heteroaryl ring system containing at least one nitrogen atom, wherein the 8-10 membered refers to the total number of atoms in the fused system.

[0117] In some embodiments, Ring A is a fused bicyclic 8-10 membered heteroaryl ring containing at least one nitrogen atom, wherein Ring A is substituted at any available positions with 0, 1, 2 or 3 instances of R ⁴ , wherein R ⁴ is as defined in any of the embodiments described herein, and wherein the 8-10 membered refers to the total number of atoms in the fused system. [0118] In some embodiments, Ring A is an optionally substituted fused bicyclic 8-10 membered heteroaryl ring system containing at least one nitrogen atom and 0, 1, 2 or 3 additional heteroatoms selected from the group consisting of N, O and S or oxidized forms thereof, wherein the 8-10 membered refers to the total number of atoms in the fused system. In some embodiments, Ring A is substituted at any available positions with 0, 1, 2 or 3 instances of R ⁴ , wherein R ⁴ is as defined in any of the embodiments described herein. [0119] In some embodiments, Ring A contains a 5-6 membered monocyclic heteroaryl ring containing at least one nitrogen atom and 0, 1 or 2 additional heteroatoms selected from the group consisting of N, O or S or oxidized forms thereof (e.g.¸ pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, oxadiazolyl, oxathiazolyl), fused to a carbocyclyl or heterocyclyl ring, wherein the total number of atoms in the fused system is between 8 and 10 and the system contains a total of 2, 3 or 4 heteroatoms selected from the group consisting of N, O and S or oxidized forms thereof. The attachment point is on the heteroaryl ring. [0120] In some embodiments, Ring A is substituted at any available positions with 0, 1, 2 or 3 instances of R ⁴ , wherein R ⁴ is as defined in any of the embodiments described herein. [0121] In some embodiments, Ring A contains a 5-6 membered monocyclic heteroaryl ring containing at least one nitrogen atom and 0, 1 or 2 additional heteroatoms selected from the group consisting of N, O or S or oxidized forms thereof (e.g.¸ pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, oxadiazolyl, oxathiazolyl), fused to a carbocyclyl ring, wherein the total number of atoms in the fused system is between 8 and 10. In some embodiments, Ring A is substituted at any available positions with 0, 1, 2 or 3 instances of R ⁴ , wherein R ⁴ is as defined in any of the embodiments described herein. [0122] In some embodiments, Ring A contains a 5-6 membered monocyclic heteroaryl ring containing at least one nitrogen atom and 0, 1 or 2 additional heteroatoms selected from the group consisting of N, O or S or oxidized forms thereof (e.g.¸ pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, oxadiazolyl, oxathiazolyl), fused to a heterocyclyl ring, wherein the total number of atoms in the fused system is between 8 and 10 and the system contains a total of 2, 3 or 4 heteroatoms selected from the group consisting of N, O and S or oxidized forms thereof. In some embodiments, Ring A is substituted at any available positions with 0, 1, 2 or 3 instances of R ⁴ , wherein R ⁴ is as defined in any of the embodiments described herein. [0123] In some embodiments, Ring A contains a phenyl ring fused with a 5-6 membered monocyclic heteroaryl ring containing at least one nitrogen atom and 0, 1 or 2 additional heteroatoms selected from the group consisting of N, O or S or oxidized forms thereof (e.g.,¸ pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, oxadiazolyl, oxathiazolyl), wherein the attachment point is on either the phenyl or the heteroaryl ring. In some embodiments, Ring A is substituted at any available positions with 0, 1, 2 or 3 instances of R ⁴ , wherein R ⁴ is as defined in any of the embodiments described herein. [0124] In some embodiments, Ring A is selected from the group consisting of: wherein: each of rings A ¹ , A ² and A ⁴ is independently 4-6 membered carbocyclyl, 4-6 membered heterocyclyl, 5-6 membered heteroaryl or phenyl; each rings A ³ is independently a 4-6 membered heterocyclyl or 5-6 membered heteroaryl, wherein the heterocyclyl and heteroaryl contain at least one nitrogen atom; each ring A ⁵ is independently a 5-6 membered heteroaryl, wherein the heteroaryl contains at least one nitrogen atom; each R ⁴ is independently selected from the group consisting of –D, halo, =O, –CN, – C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a4 , –N(R ^a4 ) ₂ , –C(=O)R ^a4 , –C(=O)OR ^a4 , –NR ^a4 C(=O)R ^a4 , –NR ^a4 C(=O)OR ^a4 , –C(=O)N(R ^a4 ) ₂ , – C(=O)N(OR ^a4 )(R ^a4 ), –OC(=O)N(R ^a4 ) ₂ , –S(=O)R ^a4 , –S(=O) ₂ R ^a4 , –SR ^a4 , –S(=O)(=NR ^a4 )R ^a4 , – NR ^a4 S(=O) ₂ R ^a4 and –S(=O) ₂ N(R ^a4 ) ₂ ; each R ^a4 is independently selected from the group consisting of H, –C ₁ –C ₆ alkyl, –C ₁ – C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, C ₆ -C ₁₀ aryl, 5-10 membered heteroaryl, arylalkyl and heteroarylalkyl wherein each alkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is independently selected from the group consisting of =O, halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, – OR ^b , –N(R ^b ) ₂ , –C(=O)R ^b , –C(=O)OR ^b , –NR ^b C(=O)R ^b , –NR ^b C(=O)OR ^b , –C(=O)N(R ^b ) ₂ , – OC(=O)N(R ^b ) ₂ , –S(=O)R ^b , –S(=O) ₂ R ^b , –SR ^b , –S(=O)(=NR ^b )R ^b , –NR ^b S(=O) ₂ R ^b and – S(=O) ₂ N(R ^b ) ₂ , wherein each R ^b is independently selected from the group consisting of H, – C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu)), and C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl); and m is 0, 1, 2 or 3. [0125] In one embodiment, rings A ¹ , A ² , and A ⁴ are each independently a 4-6 membered carbocyclyl, a 4-6 membered heterocyclyl containing 1, 2 or 3 heteroatoms selected from the group consisting of O, N, S or oxidized forms thereof, a 5-6 membered heteroaryl containing 1, 2 or 3 heteroatoms selected from the group consisting of O, N, S or oxidized forms thereof or a phenyl. [0126] In one embodiment, each ring A ³ is independently a 4-6 membered heterocyclyl or 5-6 membered heteroaryl, wherein the heterocyclyl and heteroaryl contain at least one nitrogen atom and 0, 1 or 2 additional heteroatoms selected from the group consisting of N, O or S or oxidized forms thereof. In one embodiment, each ring A ⁵ is independently a 5-6 membered heteroaryl, wherein the heteroaryl contains at least one nitrogen atom and 0, 1 or 2 additional heteroatoms selected from the group consisting of N, O or S or oxidized forms thereof. [0127] In one embodiment, Ring A is wherein A ¹ , R ⁴ and m are as defined in any of the embodiments described herein. [0128] In one embodiment, ring A is defined in any of the embodiments described herein.

[0129] In one embodiment, ring A is wherein A ³ , R ⁴ and m are as defined in any of the embodiments described herein.

[0130] In one embodiment, ring A is wherein A ⁴ , R ⁴ and m are as defined in any of the embodiments described herein.

[0131] In one embodiment, ring A is any of the embodiments described herein.

[0132] In some embodiments, Ring A is selected from the group consisting of: wherein R ⁴ and m are as defined in any of the embodiments described herein. [0133] In some embodiments, Ring A is selected from the group consisting of: wherein R ⁴ and m are as defined in any of the embodiments described herein. [0134] In some embodiments, Ring A is selected from the group consisting of: [0135] In some embodiments, Ring A is selected from the group consisting of: 4 wherein R and m are as defined in any of the embodiments described herein. [0136] In some embodiments, Ring A is selected from the group consisting of: wherein R ⁴ and m are as defined in any of the embodiments described herein. [0137] In some embodiments, Ring A is selected from the group consisting of: wherein R ⁴ and m are as defined in any of the embodiments described herein. [0138] In certain embodiments, Ring A is selected from the group consisting of: wherein R ⁴ and m are as defined in any of the embodiments described herein. [0139] In some embodiments, ring A is: wherein R ⁴ and m are as defined in any of the embodiments described herein. [0140] In some embodiments, ring A is: wherein R ⁴ and m are as defined in any of the embodiments described herein. [0141] In some embodiments, ring A is: , wherein R ⁴ and m are as defined in any of the embodiments described herein.

[0142] In some embodiments, ring A is: , wherein R ⁴ and m are as defined in any of the embodiments described herein.

[0143] In some embodiments, ring A is: , wherein R ⁴ and m are as defined in any of the embodiments described herein.

[0144] In some embodiments, ring A is: , wherein R ⁴ and m are as defined in any of the embodiments described herein.

[0145] In some embodiments, ring A is: , wherein R ⁴ and m are as defined in any of the embodiments described herein.

[0146] In some embodiments, ring A is: wherein R ⁴ and m are as defined in any of the embodiments described herein. [0147] In some embodiments, ring A is: wherein R ⁴ and m are as defined in any of the embodiments described herein. [0148] In some embodiments, ring A is: wherein R ⁴ and m are as defined in any of the embodiments described herein. [0149] In some embodiments, ring A is: wherein R ⁴ and m are as defined in any of the embodiments described herein. [0150] In some embodiments, ring A is: wherein R ⁴ and m are as defined in any of the embodiments described herein. [0151] As generally defined herein, m is 0, 1, 2 or 3. In some embodiments, m is 0, 1 or 2. [0152] In some embodiments, m is 0 or 1. In some embodiments, m is 1 or 2. [0153] In some embodiments, m is 0. [0154] In some embodiments, m is 1. [0155] In some embodiments, m is 2. [0156] In some embodiments, m is 3. [0157] In some embodiments, Ring A is selected from the group consisting of:

and wherein R ⁴ is as defined in any of the embodiments described herein. [0158] In some embodiments, Ring A is selected from the group consisting of: wherein R ⁴ is as defined in any of the embodiments described herein. [0159] In some embodiments, Ring A is selected from the group consisting of: wherein R ⁴ is as defined in any of the embodiments described herein.

[0160] In some embodiments, Ring A is selected from the group consisting of: wherein R ⁴ is as defined in any of the embodiments described herein.

[0161] In some embodiments, Ring A is selected from the group consisting of:

[0162] In some embodiments, Ring A is wherein R ⁴ is as defined in any of the embodiments described herein. In some embodiments, Ring A is wherein R ⁴ is as defined in any of the embodiments described herein. In some embodiments, Ring A is

[0163] In some embodiments, Ring A is selected from the group consisting of:

[0164] In some embodiments, Ring A is selected from the group consisting of:

[0165] In some embodiments, Ring A is selected from the group consisting of:

[0166] In some embodiments, Ring A is selected from the group consisting of:

[0167] In some embodiments, Ring A is selected from the group consisting of:

[0168] In some embodiments, Ring A is selected from the group consisting of: [0169] In certain embodiments, Ring A is selected from the group consisting of: [0170] In certain embodiments, Ring A is selected from the group consisting of: [0171] In certain embodiments, Ring A is selected from the group consisting of: [0172] In certain embodiments, Ring A is selected from the group consisting of: [0173] In certain embodiments, Ring A is selected from the group consisting of:

[0174] In some embodiments the compounds of Formula (I) are of Formula (II1):

wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein. In some embodiments, the compounds are of Formula (II1a): ^{1 2 4} wherein Ring B, R , R , R , m and n are as defined in any of the embodiments described herein. [0175] In some embodiments the compounds of Formula (I) are of Formula (II2): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein. [0176] In some embodiments, the compounds are of Formula (II2a): wherein Ring B, R ^{1 2 4} , R , R , m and n are as defined in any of the embodiments described herein. [0177] In yet some embodiments, the compounds are of Formula (II2b): where ^{1 2} in Ring B, R , R , and n are as defined in any of the embodiments described herein. [0178] In yet some embodiments, the compounds are of Formula (II2c): wherein Ring B, R ¹ , R ² , and n are as defined in any of the embodiments described herein. [0179] In other embodiments, the compounds are of Formula (II2d): wherein Ring B, R ¹ , R ² , and n are as defined in any of the embodiments described herein. [0180] In other embodiments, the compounds are of Formula (II2e): wherei ^{1 2} n Ring B, R , R , and n are as defined in any of the embodiments described herein. [0181] In some embodiments the compounds of Formula (I) are of Formula (II3): wher ^{1 2 4} ein Ring B, R , R , R , m and n are as defined in any of the embodiments described herein. [0182] In some embodiments, the compounds are of Formula (II3a): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein. [0183] In some embodiments, the compounds are of Formula (II3b): wherein Ring B, R ¹ , R ² and n are as defined in any of the embodiments described herein. [0184] In some embodiments, the compounds are of Formula (II3c): wherein Ring B, R ¹ , ² R and n are as defined in any of the embodiments described herein. [0185] In some embodiments, the compounds are of Formula (II3d): wherein Ring B, R ¹ , R ² and n are as defined in any of the embodiments described herein. [0186] In some embodiments, the compounds are of Formula (II3e): wherein Ring B, R ¹ , R ² and n are as defined in any of the embodiments described herein. [0187] In some embodiments, the compounds are of Formula (II3f): wherein Ring B, R ¹ , R ² and n are as defined in any of the embodiments described herein. [0188] In some embodiments, the compounds are of Formula (II3g): wherein Ring B, R ¹ , R ² and n are as defined in any of the embodiments described herein. [0189] In some embodiments, the compounds are of Formula (II3h): wherein Ring B, R ¹ , R ² and n are as defined in any of the embodiments described herein.

[0190] In some embodiments the compounds of Formula (I) are of Formula (114): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein.

[0191] In some embodiments, the compounds are of Formula (II4a): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein.

[0192] In some embodiments, the compounds are of Formula (II4b): wherein Ring B, R ¹ , R ² and n are as defined in any of the embodiments described herein. [0193] In some embodiments, the compounds are of Formula (II4c): wherein Ring B, R ¹ , R ² and n are as defined in any of the embodiments described herein. [0194] In some embodiments the compounds of Formula (I) are of Formula (II5): wherein R ^{1 2 4} ing B, R, R, R, m and n are as defined in any of the embodiments described herein. [0195] In some embodiments, the compounds are of Formula (II5a): wherein Ring B ^{1 2 4} , R, R, R, m and n are as defined in any of the embodiments described herein. [0196] In some embodiments the compounds of Formula (I) are of Formula (II6): wherei ^{1 2 4} n Ring B, R, R, R, m and n are as defined in any of the embodiments described herein. [0197] In some embodiments, the compounds are of Formula (II 6a): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein.

[0198] In some embodiments the compounds of Formula (I) are of Formula (117): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein.

[0199] In some embodiments, the compounds are of Formula (II7a): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein.

[0200] In some embodiments, the compounds are of Formula (II7b): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein. [0201] In yet some embodiments, the compounds are of Formula (II7c): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein.

[0202] In other embodiments, the compounds are of Formula (II7d): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein.

[0203] In some embodiments the compounds of Formula (I) are of Formula (118): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein.

[0204] In some embodiments, the compounds are of Formula (II8a): defined in any of the embodiments described herein.

[0205] In some embodiments the compounds of Formula (I) are of Formula (119): are as defined in any of the embodiments described herein.

[0206] In some embodiments, the compounds are of Formula (II9a): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein.

[0207] In some embodiments the compounds of Formula (I) are of Formula (II 10): defined in any of the embodiments described herein.

[0208] In some embodiments, the compounds are of Formula (II 10a): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein. [0209] In some embodiments, the compounds are of Formula (II 10b): any of the embodiments described herein.

[0210] In some embodiments, the compounds are of Formula (II 10c): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein.

[0211] In some embodiments the compounds of Formula (I) are of Formula (III 1): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein. [0212] In some embodiments, the compounds are of Formula (III la): la) wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein. [0213] In some embodiments, the compounds are of Formula (III lb): lb) wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein.

[0214] In some embodiments, the compounds are of Formula (III lc): lc) wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein.

[0215] In some embodiments, the compounds are of Formula (III Id): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein.

[0216] In some embodiments, the compounds are of Formula (III le): le) wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein.

[0217] In some embodiments the compounds of Formula (I) are of Formula (1112):

wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein.

[0218] In some embodiments, the compounds are of Formula (II12a): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein.

[0219] In some embodiments, the compounds are of Formula (II 12b): defined in any of the embodiments described herein.

[0220] In some embodiments, the compounds are of Formula (II 12c): wherein Ring B, R ¹ , R ² , R ⁴ , m and n are as defined in any of the embodiments described herein. [0221] As generally defined herein, each R ⁴ is independently selected from the group consisting of –D, halo, =O, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ – C9 cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a4 , –N(R ^a4 ) ₂ , –C(=O)R ^a4 , –C(=O)OR ^a4 , –NR ^a4 C(=O)R ^a4 , – NR ^a4 C(=O)OR ^a4 , –C(=O)N(R ^a4 ) ₂ , –C(=O)N(OR ^a4 )(R ^a4 ), –OC(=O)N(R ^a4 ) ₂ , –S(=O)R ^a4 , – S(=O) ₂ R ^a4 , –SR ^a4 , –S(=O)(=NR ^a4 )R ^a4 , –NR ^a4 S(=O) ₂ R ^a4 and –S(=O) ₂ N(R ^a4 ) ₂ , wherein R ^a4 is as defined in any of the embodiments described herein. [0222] In some embodiments, each R ⁴ is independently selected from the group consisting of halo, =O, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, – OR ^a4 , –N(R ^a4 ) ₂ , –C(=O)R ^a4 , –C(=O)OR ^a4 , –NR ^a4 C(=O)R ^a4 , –NR ^a4 C(=O)OR ^a4 , – C(=O)N(R ^a4 ) ₂ , –C(=O)N(OR ^a4 )(R ^a4 ), –OC(=O)N(R ^a4 ) ₂ , –S(=O)R ^a4 , –S(=O) ₂ R ^a4 , –SR ^a4 , – S(=O)(=NR ^a4 )R ^a4 , –NR ^a4 S(=O) ₂ R ^a4 and –S(=O) ₂ N(R ^a4 ) ₂ , wherein R ^a4 is as defined in any of the embodiments described herein. [0223] In some embodiments, R ⁴ is selected from the group consisting of –D, halo, =O, – CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a4 , –N(R ^a4 ) ₂ , –C(=O)R ^a4 , –C(=O)OR ^a4 , –NR ^a4 C(=O)R ^a4 , –NR ^a4 C(=O)OR ^a4 , –C(=O)N(R ^a4 ) ₂ , – C(=O)N(OR ^a4 )(R ^a4 ), –OC(=O)N(R ^a4 ) ₂ , –S(=O)R ^a4 , –S(=O) ₂ R ^a4 , –SR ^a4 , –S(=O)(=NR ^a4 )R ^a4 , – NR ^a4 S(=O) ₂ R ^a4 and –S(=O) ₂ N(R ^a4 ) ₂ , wherein R ^a4 is as defined in any of the embodiments described herein. [0224] In some embodiments, R ⁴ is selected from the group consisting of halo, =O, –CN, – C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a4 , –N(R ^a4 ) ₂ , –C(=O)R ^a4 , –C(=O)OR ^a4 , –NR ^a4 C(=O)R ^a4 , –NR ^a4 C(=O)OR ^a4 , –C(=O)N(R ^a4 ) ₂ , – C(=O)N(OR ^a4 )(R ^a4 ), –OC(=O)N(R ^a4 ) ₂ , –S(=O)R ^a4 , –S(=O) ₂ R ^a4 , –SR ^a4 , –S(=O)(=NR ^a4 )R ^a4 , – NR ^a4 S(=O) ₂ R ^a4 and –S(=O) ₂ N(R ^a4 ) ₂ , wherein R ^a4 is as defined in any of the embodiments described herein. [0225] In certain embodiments, R ⁴ is selected from the group consisting of –D, halo, =O, – CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, –OR ^a4 , – N(R ^a4 ) ₂ , –C(=O)R ^a4 , –C(=O)OR ^a4 , –NR ^a4 C(=O)R ^a4 , –NR ^a4 C(=O)OR ^a4 , –C(=O)N(R ^a4 ) ₂ , – C(=O)N(OR ^a4 )(R ^a4 ) and –OC(=O)N(R ^a4 ) ₂ , wherein R ^a4 is as defined in any of the embodiments described herein. [0226] In certain embodiments, R ⁴ is selected from the group consisting of halo, =O, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, –OR ^a4 , –N(R ^a4 ) ₂ , – C(=O)R ^a4 , –C(=O)OR ^a4 , –NR ^a4 C(=O)R ^a4 , –NR ^a4 C(=O)OR ^a4 , –C(=O)N(R ^a4 ) ₂ , – C(=O)N(OR ^a4 )(R ^a4 ) and –OC(=O)N(R ^a4 ) ₂ , wherein R ^a4 is as defined in any of the embodiments described herein. [0227] In some embodiments, R ⁴ is selected from the group consisting of –D, =O, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, –OR ^a4 and –N(R ^a4 ) ₂ , wherein R ^a4 is as defined in any of the embodiments described herein. [0228] In some embodiments, R ⁴ is selected from the group consisting of =O, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, –OR ^a4 and –N(R ^a4 ) ₂ , wherein R ^a4 is as defined in any of the embodiments described herein. [0229] In some embodiments, R ⁴ is selected from the group consisting of –D, =O, –C ₁ –C ₆ alkyl and –N(R ^a4 ) ₂ , wherein R ^a4 is as defined in any of the embodiments described herein. [0230] In some embodiments, R ⁴ is selected from the group consisting of =O, –C ₁ –C ₆ alkyl and –N(R ^a4 ) ₂ , wherein R ^a4 is as defined in any of the embodiments described herein. [0231] In certain embodiments, R ⁴ is selected from the group consisting of –D, =O, –Me, – Et, – ⁱ Pr, – ^t Bu, –NH ₂ , –NHCH ₃ and –NH(CH ₃ ) ₂ . In certain embodiments, R ⁴ is selected from the group consisting of =O, –Me, –Et, – ⁱ Pr, – ^t Bu, –NH ₂ , –NHCH ₃ and –NH(CH ₃ ) ₂ . In some embodiments, R ⁴ is selected from the group consisting of –NHCH ₃ , –NH ₂ or –Me. In some embodiments, R ⁴ is selected from the group consisting of –NH ₂ or –Me. [0232] In some embodiments, R ⁴ is =O. [0233] In some embodiments, R ⁴ is –D. [0234] In certain embodiments, R ⁴ is halo (e.g., fluoro, chloro, bromo, iodo). In some embodiments, R ⁴ is –Cl. In some embodiments, R ⁴ is –F. In some embodiments, R ⁴ is –Br. In some embodiments, R ⁴ is –I. [0235] In some embodiments, R ⁴ is –CN. [0236] In certain embodiments, R ⁴ is –C ₁ –C ₆ alkyl. In some embodiments, R ⁴ is –Me. In some embodiments, R ⁴ is –Et. In some embodiments R ⁴ is –Pr or –iPr. [0237] In some embodiments, R ⁴ is –C ₁ –C ₆ heteroalkyl. In some embodiments, R ⁴ is methoxymethyl (–CH ₂ OCH ₃ ). In some embodiments, R ⁴ is hydroxymethyl (–CH ₂ OH). In some embodiments, R ⁴ is aminomethyl (e.g.,–CH ₂ NH ₂ , –CH ₂ NHCH ₃ , –CH ₂ N(CH ₃ ) ₂ . [0238] In some embodiments, R ⁴ is –C ₁ –C ₆ haloalkyl. In some embodiments, R ⁴ is trifluoromethyl (–CF ₃ ). In other embodiments, R ⁴ is difluoromethyl (–CHF ₂ ). [0239] In some embodiments, R ⁴ is C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl). In some embodiments, R ⁴ is cyclopropyl. In some embodiments R ⁴ is cyclobutyl. In some embodiments, R ⁴ is cyclopentyl. In some embodiments, R ⁴ is cyclohexyl. [0240] In some embodiments, R ⁴ is 3-10 membered heterocyclyl. In some embodiments, R ⁴ is 3-6 membered heterocyclyl (e.g., oxetanyl, tetrahydropyranyl, tetrahydrofuranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl). In some embodiments, R ⁴ is oxetanyl. In some embodiments, R ⁴ is tetrahydropyranyl. In some embodiments, R ⁴ is tetrahydrofuranyl. In some embodiments, R ⁴ is azetidinyl. In some embodiments, R ⁴ is pyrrolidinyl. In some embodiments, R ⁴ is piperidinyl. In some embodiments, R ⁴ is piperazinyl. In some embodiments, R ⁴ is morpholinyl. In some embodiments, R ⁴ is azepanyl. [0241] In some embodiments R ⁴ is cycloalkylalkyl (e.g., cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl). [0242] In some embodiments, R ⁴ is heterocyclylalkyl (e.g., oxetanylmethyl, aziridinylmethyl, tetrahydrofuranylmethyl, pyrrolidinylmethyl, tetrahydropyranylmethyl, piperidinylmethyl, piperazinylmethyl, morpholinylmethyl, azepanylmethyl). [0243] In some embodiments, R ⁴ is arylalkyl. In some embodiments, R ⁴ is benzyl. [0244] In some embodiments, R ⁴ is heteroarylalkyl (e.g., pyridinylmethyl, thiazolylmethyl, triazolylmethyl, pyrazolylmethyl). [0245] In some embodiments, R ⁴ is –OR ^a4 wherein R ^a4 is as defined in any of the embodiments described herein (e.g., hydroxy (–OH), methoxy, ethoxy, propoxy, isopropoxy, cyclopropyloxy, cyclobutyloxy). In some embodiments, R ⁴ is hydroxy. In some embodiments, R ⁴ is methoxy. In some embodiments, R ⁴ is ethoxy. In some embodiments, R ⁴ is propoxy. In some embodiments, R ⁴ is isopropoxy. In some embodiments, R ⁴ is –C ₁ –C ₆ haloalkoxy. In some embodiments, R ⁴ is trifluoromethoxy (–OCF ₃ ), In other embodiments, R ⁴ is difluoromethoxy (–OCHF ₂ ). [0246] In some embodiments, R ⁴ is –N(R ^a4 ) ₂ wherein R ^a4 is as defined in any of the embodiments described herein (e.g., –NH ₂ , –NHR ^a4 , –N(CH ₃ )R ^a4 ). In some embodiments, R ⁴ is –NH ₂ . In some embodiments, R ⁴ is –NHR ^a4 (e.g., –NHCH ₃ , –NHCH ₂ CH ₃ , –NHPr, – NH ⁱ Pr, –NHcyclopropyl, –NHcyclobutyl). In some embodiments, R ⁴ is –N(CH ₃ )R ^a4 (e.g., – N(CH ₃ ) ₂ , –N(CH ₃ )CH ₂ CH ₃ , –N(CH ₃ )CH ₂ CH ₂ CH ₃ , –N(CH ₃ ) ⁱ Pr, –N(CH ₃ )cyclopropyl, – N(CH ₃ )cyclobutyl). [0247] In some embodiments, R ⁴ is –C(=O)R ^a4 or –C(=O)OR ^a4 wherein R ^a4 is as defined in any of the embodiments described herein. In some embodiments, R ⁴ is –C(=O)R ^a4 wherein R ^a4 is as defined in any of the embodiments described herein. In some embodiments, R ⁴ is – C(=O)alkyl. In some embodiments, R ⁴ is –C(=O)CH ₃ , –C(=O)cyclopropyl, – C(=O)cyclobutyl, –C(=O) ^t Bu, –C(=O) ⁱ Pr, –C(=O)CH ₂ CH ₂ CH ₃ or –C(=O)OCH ₃ . In some embodiments, R ⁴ is acetyl (–C(=O)CH ₃ ). In some embodiments, R ⁴ is –C(=O)OR ^a4 . In some embodiments, R ⁴ is –COOH. In some embodiments, R ⁴ is COOCH ₃ . [0248] In some embodiments, R ⁴ is –NR ^a4 C(=O)R ^a4 wherein R ^a4 is as defined in any of the embodiments described herein. In certain embodiments, R ⁴ is –NHC(=O)R ^a4 (e.g., – NHC(=O)CH ₃ , –NHC(=O)CH ₂ CH ₃ , –NHC(=O)CH ₂ CH ₂ CH ₃ , –NHC(=O) ⁱ Pr, –NHC(=O)Bu, –NHC(=O) ^t Bu, –NHC(=O)Cyclopropyl, –NHC(=O)Cyclobutyl). In some embodiments, R ⁴ is –N(CH ₃ )C(=O)R ^a4 (e.g., –N(CH ₃ )C(=O)CH ₃ , –N(CH ₃ )C(=O)CH ₂ CH ₃ , – N(CH ₃ )C(=O)CH ₂ CH ₂ CH ₃ , –N(CH ₃ )C(=O) ⁱ Pr, –N(CH ₃ )C(=O)Bu, –N(CH ₃ )C(=O) ^t Bu, – N(CH ₃ )C(=O)Cyclopropyl, –N(CH ₃ )C(=O)Cyclobutyl). [0249] In some embodiments, R ⁴ is –NR ^a4 C(=O)OR ^a4 wherein R ^a4 is as defined in any of the embodiments described herein. In certain embodiments, R ⁴ is –NHC(=O)OR ^a4 (e.g., – NHC(=O)OCH ₃ , –NHC(=O)OCH ₂ CH ₃ , –NHC(=O)OCH ₂ CH ₂ CH ₃ , –NHC(=O)O ⁱ Pr, – NHC(=O)OBu, –NHC(=O)O ^t Bu, –NHC(=O)OCyclopropyl, –NHC(=O)OCyclobutyl). In some embodiments, R ⁴ is –N(CH ₃ )C(=O)OR ^a4 (e.g., –N(CH ₃ )C(=O)OCH ₃ , – N(CH ₃ )C(=O)OCH ₂ CH ₃ , –N(CH ₃ )C(=O)OCH ₂ CH ₂ CH ₃ , –N(CH ₃ )C(=O)O ⁱ Pr, – N(CH ₃ )C(=O)OBu, –N(CH ₃ )C(=O)O ^t Bu, –N(CH ₃ )C(=O)OCyclopropyl, – N(CH ₃ )C(=O)OCyclobutyl). [0250] In some embodiments, R ⁴ is –C(=O)N(R ^a4 ) ₂ wherein R ^a4 is as defined in any of the embodiments described herein (e.g., –C(=O)NH ₂ , –C(=O)NHR ^a4 , –C(=O)N(CH ₃ )R ^a4 ). In some embodiments, R ⁴ is –C(=O)NH ₂ . In certain embodiments, R ⁴ is –C(=O)NHR ^a4 (e.g., – C(=O)NHCH ₃ , –C(=O)NHCH ₂ CH ₃ , –C(=O)NHPr, –C(=O)NH ⁱ Pr, –C(=O)NHBu, – C(=O)NH ^t Bu, –C(=O)NHCyclopropyl, –C(=O)NHCyclobutyl). In certain embodiments, R ⁴ is –C(=O)N(CH ₃ )R ^a4 (e.g., –C(=O)N(CH ₃ ) ₂ , –C(=O)N(CH ₃ )CH ₂ CH ₃ , – C(=O)N(CH ₃ )CH ₂ CH ₂ CH ₃ , –C(=O)N(CH ₃ ) ⁱ Pr, –C(=O)N(CH ₃ )Bu, –C(=O)N(CH ₃ ) ^t Bu, – C(=O)N(CH ₃ )Cyclopropyl, –C(=O)N(CH ₃ )Cyclobutyl). [0251] In some embodiments, R ⁴ is –C(=O)N(OR ^a4 )(R ^a4 ) wherein R ^a4 is as defined in any of the embodiments described herein. In certain embodiments, R ⁴ is –C(=O)NH(OR ^a4 ) (e.g., –C(=O)NHOH, –C(=O)NHOCH ₃ ). In some embodiments, R ⁴ is –C(=O)NHOH. [0252] In some embodiments, R ⁴ is –OC(=O)N(R ^a4 ) ₂ wherein R ^a4 is as defined in any of the embodiments described herein. In certain embodiments, R ⁴ is –OC(=O)NHR ^a4 (e.g., – OC(=O)NHCH ₃ , –OC(=O)NHCH ₂ CH ₃ , –OC(=O)NHPr, –OC(=O)NH ⁱ Pr, –OC(=O)NHBu, – OC(=O)NH ^t Bu, –OC(=O)NHCyclopropyl, –OC(=O)NHCyclobutyl). In certain embodiments, R ⁴ is –OC(=O)N(CH ₃ )R ^a4 (e.g., –OC(=O)N(CH ₃ ) ₂ , –OC(=O)N(CH ₃ )CH ₂ CH ₃ , –OC(=O)N(CH ₃ )CH ₂ CH ₂ CH ₃ , –OC(=O)N(CH ₃ ) ⁱ Pr, –OC(=O)N(CH ₃ )Bu, – OC(=O)N(CH ₃ ) ^t Bu, –OC(=O)N(CH ₃ )Cyclopropyl, –OC(=O)N(CH ₃ )Cyclobutyl). [0253] In some embodiments, R ⁴ is –S(=O)R ^a4 wherein R ^a4 is as defined in any of the embodiments described herein. In certain embodiments, R ⁴ is –S(=O)alkyl (e.g., –S(=O)CH ₃ , –S(=O)CH ₂ CH ₃ , –S(=O)CH ₂ CH ₂ CH ₃ , –S(=O) ⁱ Pr). In certain embodiments, R ⁴ is – S(=O)cycloalkyl (e.g., –S(=O)cyclopropyl, –S(=O)cyclobutyl, –S(=O)cyclopentyl, – S(=O)cyclohexyl). [0254] In some embodiments, R ⁴ is –S(=O) ₂ R ^a4 wherein R ^a4 is as defined in any of the embodiments described herein. In certain embodiments, R ⁴ is –S(=O) ₂ alkyl (e.g., – S(=O) ₂ CH ₃ , –S(=O) ₂ CH ₂ CH ₃ , –S(=O) ₂ Pr, –S(=O) ₂ ⁱ Pr). In certain embodiments, R ⁴ is – S(=O) ₂ cycloalkyl (e.g., –S(=O) ₂ cyclopropyl, –S(=O) ₂ cyclobutyl, –S(=O) ₂ cyclopentyl, – S(=O) ₂ cyclohexyl). In some embodiments, R ⁴ is S(=O) ₂ aryl (e.g., –S(=O) ₂ phenyl). [0255] In some embodiments, R ⁴ is –SR ^a4 wherein R ^a4 is as defined in any of the embodiments described herein. In certain embodiments, R ⁴ is –Salkyl (e.g., –SCH ₃ , – SCH ₂ CH ₃ , –SPr, –S ⁱ Pr). In certain embodiments, R ⁴ is –Scycloalkyl (e.g., –Scyclopropyl, – Scyclobutyl, –Scyclopentyl, –Scyclohexyl). In certain embodiments, R ⁴ is –Saryl (e.g., – Sphenyl). In some embodiments, R ⁴ is –S(=O)(=NR ^a4 )R ^a4 wherein R ^a4 is as defined in any of the embodiments described herein. In certain embodiments, R ⁴ is –S(=O)(=NH)R ^a4 (e.g., – S(=O)(=NH)CH ₃ , –S(=O)(=NH)CH ₂ CH ₃ , –S(=O)(=NH)CH ₂ CH ₂ CH ₃ , –S(=O)(=NH) ⁱ Pr, – S(=O)(=NH)Bu, –S(=O)(=NH) ^t Bu, –S(=O)(=NH)Cyclopropyl, –S(=O)(=NH)Cyclobutyl). In some embodiments, R ⁴ is –S(=O)(=NCH ₃ )R ^a4 (e.g., –S(=O)(=NCH ₃ )CH ₃ , – S(=O)(=NCH ₃ )CH ₂ CH ₃ , –S(=O)(=NCH ₃ )CH ₂ CH ₂ CH ₃ , –S(=O)(=NCH ₃ ) ⁱ Pr, – S(=O)(=NCH ₃ )Bu, –S(=O)(=NCH ₃ ) ^t Bu, –S(=O)(=NCH ₃ )Cyclopropyl, – S(=O)(=NCH ₃ )Cyclobutyl). [0256] In some embodiments, R ⁴ is –NR ^a4 S(=O) ₂ R ^a4 wherein R ^a4 is as defined in any of the embodiments described herein. In certain embodiments, R ⁴ is –NHS(=O) ₂ alkyl (e.g., – NHS(=O) ₂ CH ₃ , –NHS(=O) ₂ CH ₂ CH ₃ , –NHS(=O) ₂ Pr, –NHS(=O) ₂ ⁱ Pr). In certain embodiments, R ⁴ is –NHS(=O) ₂ cycloalkyl (e.g., –NHS(=O) ₂ cyclopropyl, – NHS(=O) ₂ cyclobutyl, –NHS(=O) ₂ cyclopentyl, –NHS(=O) ₂ cyclohexyl). In certain embodiments, R ⁴ is –N(CH ₃ )S(=O) ₂ alkyl (e.g., –N(CH ₃ )S(=O) ₂ CH ₃ , – N(CH ₃ )S(=O) ₂ CH ₂ CH ₃ , –N(CH ₃ )S(=O) ₂ Pr, –N(CH ₃ )S(=O) ₂ ⁱ Pr). In certain embodiments, R ⁴ is –N(CH ₃ )S(=O) ₂ cycloalkyl (e.g., –N(CH ₃ )S(=O) ₂ cyclopropyl, –N(CH ₃ )S(=O) ₂ cyclobutyl, – N(CH ₃ )S(=O) ₂ cyclopentyl, –N(CH ₃ )S(=O) ₂ cyclohexyl). [0257] In some embodiments, R ⁴ is –S(=O) ₂ N(R ^a4 ) ₂ wherein R ^a4 is as defined in any of the embodiments described herein. (e.g., –S(=O) ₂ NH ₂ , –S(=O) ₂ NHR ^a4 , –S(=O) ₂ N(CH ₃ )R ^a4 ). In some embodiments, R ⁴ is –S(=O) ₂ NH ₂ . In some embodiments, R ⁴ is –S(=O) ₂ NHR ^a4 (e.g., – S(=O) ₂ NHCH ₃ , –S(=O) ₂ NHCH ₂ CH ₃ , –S(=O) ₂ NHPr, –S(=O) ₂ NH ⁱ Pr, –S(=O) ₂ NHcyclopropyl, –S(=O) ₂ NHcyclobutyl). In some embodiments, R ⁴ is –S(=O) ₂ N(CH ₃ )R ^a4 (e.g., – S(=O) ₂ N(CH ₃ ) ₂ , –S(=O) ₂ N(CH ₃ )CH ₂ CH ₃ , –S(=O) ₂ N(CH ₃ )CH ₂ CH ₂ CH ₃ , –S(=O) ₂ N(CH ₃ ) ⁱ Pr, –S(=O) ₂ N(CH ₃ )cyclopropyl, –S(=O) ₂ N(CH ₃ )cyclobutyl). [0258] As generally defined herein, Ring B is selected from the group consisting of –C ₃ – C ₁₀ carbocyclyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl and 5-10 membered heteroaryl wherein each carbocyclyl, heterocyclyl, aryl and heteroaryl is optionally substituted at any available position. [0259] In some embodiments, each carbocyclyl, heterocyclyl, aryl and heteroaryl of Ring B is substituted at any available position with 0, 1, 2 or 3 instances of R ³ , wherein each R ³ is as defined in any of the embodiments described herein. [0260] In some embodiments, Ring B is independently selected from the group consisting of a –C ₃ –C ₁₀ monocyclic or bicyclic carbocyclyl (e.g., a –C ₃ –C ₁₀ monocyclic or bicyclic cycloalkyl, a partially unsaturated –C ₃ –C ₁₀ monocyclic or bicyclic carbocyclyl, a –C ₃ –C ₇ monocyclic carbocyclyl fused with phenyl or with a 5-6-membered heterocyclyl or heteroaryl ring containing 1-3 atoms independently selected from the group consisting of N, O, S or oxidized forms thereof), 3-10 membered mono or bicyclic heterocyclyl (e.g., a 3-8 membered monocyclic heterocyclyl containing 1-3 heteroatoms selected from the group consisting of N, O and S or oxidized forms thereof, a 4-10 membered bicyclic heterocyclyl containing 1-3 heteroatoms independently selected from the group consisting of N, O and S or oxidized forms thereof), –C ₆ –C ₁₀ mono or bicyclic aryl (e.g., phenyl, fully aromatic 9-10 membered bicyclic aryl, bicyclic aryl containing a phenyl ring fused with a C ₅ -C6 carbocycle, bicyclic aryl containing a phenyl ring fused with a 5-6 membered heterocycle containing 1-3 heteroatoms independently selected from the group consisting of N, O and S or oxidized forms thereof), 5-6 membered monocyclic heteroaryl (e.g., containing 1-4 heteroatoms independently selected from the group consisting of N, O and S), 8-10 membered bicyclic heteroaryl (e.g., containing 1-4 heteroatoms independently selected from the group consisting of N, O and S) wherein each carbocyclyl, heterocyclyl, aryl and heteroaryl is optionally substituted (e.g., substituted with 0, 1, 2 or 3 instances of R ³ wherein R ³ is as defined in any of the embodiments described herein). [0261] In some embodiments, Ring B is selected from the group consisting of –C ₃ –C ₁₀ monocyclic or bicyclic carbocyclyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo[1.1.1]pentan-yl, 4,5,6,7-tetrahydro-1H-indazolyl, spiro[3.3]heptanyl), 3- 10 membered mono or bicyclic heterocyclyl (e.g., oxetanyl, azepanyl, piperidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, 1,2-dihydropyridinyl, morpholinyl), C6– C ₁₀ mono or bicyclic aryl (e.g., phenyl, naphthyl, 1,2,3,4-tetrahydronaphthalenyl, 2,3- dihydro-1H-indenyl, 1,2,3,4 tetrahydroquinolinyl, 1,2 dihydroquinolinyl, 1,2- dihydroisoquinolinyl, 1,2,3,4 tetrahydroisoquinolinyl, chromanyl, indolinyl, isoindolinyl, 3,4- dihydro-2H-benzo[b][1,4]oxazinyl, 2,3-dihydrobenzofuranyl, benzo[d][1,3] dioxolyl, 2,3- dihydro-1H-benzo[d]imidazolyl), 5-6 membered monocyclic heteroaryl (e.g., thiophenyl, thiazolyl, pyrazolyl, imidazolyl, oxazolyl, pyridinyl, pyrimidinyl), 8-10 membered bicyclic heteroaryl (e.g., benzo[d]isothiazolyl, indolyl, benzofuranyl, 1H-indazolyl, 2-H-indazolyl, benzo[b]thiophenyl, quinolinyl, 1,5-naphthyridinyl, 1,2-dihydro-1,5-naphthyridinyl, 1,2,3,4- tetrahydro-1,8-naphthyridinyl, isoquinolinyl, benzo[d]imidazolyl, benzo[d]thiazolyl, benzo[d]oxazolyl, [1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, imidazo[1,5- a]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl), 1H- pyrazolo[3,4-b]pyridinyl, 1H-thieno[2,3- c]pyrazolyl, 1H-thieno[3,2-c]pyrazolyl, thiazolo[5,4-b]pyridinyl) wherein each cycloalkyl, heterocyclyl, aryl and heteroaryl is optionally substituted (e.g., substituted with 0, 1, 2 or 3 instances of R ³ wherein R ³ is as defined in any of the embodiments described herein). [0262] In certain embodiments, Ring B is selected from the group consisting of C ₆ –C ₁₀ aryl and 5-10 membered heteroaryl, wherein the aryl and heteroaryl are optionally substituted (e.g., substituted at available positions with 0, 1, 2 or 3 instances of R ³ , wherein each R ³ is as defined in any of the embodiments described herein). [0263] In some embodiments, Ring B is selected from the group consisting of phenyl, naphthalenyl, C ₃ -C ₇ monocyclic cycloalkyl, 3-7 membered monocyclic heterocyclyl, 5-6 membered monocyclic heteroaryl, and 8-10 membered bicyclic heteroaryl, each optionally substituted at any available position. [0264] In some embodiments, Ring B is selected from the group consisting of C ₆ –C ₁₀ aryl and 8-10 membered bicyclic heteroaryl wherein the aryl and heteroaryl are optionally substituted (e.g., substituted at available positions with 0, 1, 2 or 3 instances of R ³ , wherein each R ³ is as defined in any of the embodiments described herein). [0265] In some embodiments, Ring B is selected from the group consisting of: [0266] In some embodiments, Ring B is selected from the group consisting of: [0267] In some embodiments, Ring B is selected from the group consisting of:

[0268] In some embodiments, Ring B is selected from the group consisting of: [0269] In some embodiments, Ring B is selected from the group consisting of: [0270] In some embodiments, Ring B is selected from the group consisting of: [0271] In some embodiments, Ring B is selected from the group consisting of: : [0272] In some embodiments, Ring B is selected from the group consisting of: [0273] In some embodiments, Ring B is selected from the group consisting of: [0274] In some embodiments, Ring B is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, thiophenyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, phenyl, naphthalenyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, indolyl, benzofuranyl, 1H- indazolyl, 2H-indazolyl, benzo[b]thiophenyl, quinolinyl, isoquinolinyl, 1,2,3,4- tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, 2,3-dihydrobenzofuranyl, 1,5- naphthyridinyl, 1,2-dihydro-1,5-naphthyridinyl, 1,2,3,4-tetrahydro-1,8-naphthyridinyl, imidazo[1,2-a]pyridinyl, imidazo[1,5-a]pyridinyl, isoquinolinyl, benzo[d]imidazolyl, benzo[d]thiazolyl, benzo[d]isothiazolyl, benzo[d]oxazolyl, [1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl),1H- pyrazolo[3,4-b]pyridinyl, 1H- thieno[2,3-c]pyrazolyl, 1H-thieno[3,2-c]pyrazolyl, thiazolo[5,4-b]pyridinyl and 1,2,3,4- tetrahydro-1,8-naphthyridinyl, each optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0275] In some embodiments, Ring B is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, thiophenyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, phenyl, naphthalenyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, indolyl, benzofuranyl, 1H- indazolyl, 2H-indazolyl, benzo[b]thiophenyl, quinolinyl, 1,5-naphthyridinyl, 1,2-dihydro-1,5- naphthyridinyl, 1,2,3,4-tetrahydro-1,8-naphthyridinyl, imidazo[1,2-a]pyridinyl, imidazo[1,5- a]pyridinyl, isoquinolinyl, benzo[d]imidazolyl, benzo[d]thiazolyl, benzo[d]isothiazolyl, benzo[d]oxazolyl, [1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, 1H-pyrazolo[4,3- b]pyridinyl),1H- pyrazolo[3,4-b]pyridinyl, 1H-thieno[2,3-c]pyrazolyl, 1H-thieno[3,2- c]pyrazolyl, thiazolo[5,4-b]pyridinyl and 1,2,3,4-tetrahydro-1,8-naphthyridinyl, each optionally substituted (e.g., substituted at available positions with 0, 1, 2 or 3 instances of R ³ , wherein each R ³ is as defined in any of the embodiments described herein). [0276] In some embodiments, Ring B is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, tetrahydropyranyl, thiophenyl, oxazolyl, pyrazolyl, phenyl, naphthalenyl, pyridinyl, 1H-indazolyl, 2H-indazolyl, quinolinyl, isoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, 2,3- dihydrobenzofuranyl and benzo[d]thiazolyl, each optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0277] In some embodiments, Ring B is selected from the group consisting of cyclobutyl, cyclopentyl, tetrahydropyranyl, pyrazolyl, thiophenyl, oxazolyl, pyridinyl, phenyl, naphthalenyl, 1H-indazolyl, 2H-indazolyl, quinolinyl, isoquinolinyl and benzo[d]thiazolyl, each optionally substituted (e.g., substituted at available positions with 0, 1, 2 or 3 instances of R ³ , wherein each R ³ is as defined in any of the embodiments described herein). [0278] In some embodiments, Ring B is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetan-3-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, pyrazol-5-yl, pyrazol-3-yl, thiophen-3-yl, oxazol-5-yl, thiazol-5-yl, pyridin-3-yl, pyridin-4-yl, phenyl, naphthalen-1-yl, naphthalen-2-yl, indol-4-yl, indol-5-yl, benzofuran-5-yl, benzofuran-6-yl, 1H indazol-5-yl, 1H indazol-4-yl, 2H-indazol-6-yl, 2H-indazol-5-yl, benzo[b]thiophen-3-yl, benzo[b]thiophen-5-yl, quinolin-6-yl, quinolin-7-yl, quinoline-3-yl, isoquinolin-6-yl, 1,2,3,4- tetrahydroquinolin-6-yl, 1,2,3,4-tetrahydroisoquinolin-6-yl, 1,2,3,4-tetrahydroisoquinolin-7- yl, 2,3-dihydrobenzofuran-4-yl, 2,3-dihydrobenzofuran-5-yl, 2,3-dihydrobenzofuran-7-yl, benzo[d]imidazo-5-yl, 1H-benzo[d]imidazol-4-yl, benzo[d]thiazol-5-yl, benzo[d]thiazol-6-yl, benzo[d]thiazol-4-yl, benzo[d]isothiazol-5-yl, benzo[d]oxazol-4-yl, benzo[d]oxazol-5-yl, [1,2,4]triazolo[4,3-a]pyridin-6-yl, imidazo[1,2-a]pyridin-6-yl, imidazo[1,2-a]pyridin-7-yl, imidazo[1,5-a]pyridin-6-yl, pyrazolo[4,3-b]pyridin-6-yl, 1H-pyrazolo[3,4-b]pyridin-5-yl, 1H- pyrazolo[3,4-b]pyridin-5-yl, 1H-pyrazolo[4,3-b]pyridin-5-yl, 1H-pyrazolo[4,3-b]pyridin-6-yl, 1H-thieno[2,3-c]pyrazol-5-yl, 1H-thieno[3,2-c]pyrazol-5-yl and thiazolo[5,4-b]pyridin-6-yl), each optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0279] In some embodiments, Ring B is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetan-3-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, pyrazol-5-yl, pyrazol-3-yl, thiophen-3-yl, oxazol- 5-yl, thiazol-5-yl, pyridin-3-yl, pyridin-4-yl, phenyl, naphthalen-1-yl, naphthalen-2-yl, indol- 4-yl, indol-5-yl, benzofuran-5-yl, benzofuran-6-yl, 1H indazol-5-yl, 1H indazol-4-yl, 2H- indazol-6-yl, 2H-indazol-5-yl, benzo[b]thiophen-3-yl, benzo[b]thiophen-5-yl, quinolin-6-yl, quinolin-7-yl, quinoline-3-yl, isoquinolin-6-yl, benzo[d]imidazo-5-yl, 1H-benzo[d]imidazol- 4-yl, benzo[d]thiazol-5-yl, benzo[d]thiazol-6-yl, benzo[d]thiazol-4-yl, benzo[d]isothiazol-5- yl, benzo[d]oxazol-4-yl, benzo[d]oxazol-5-yl, [1,2,4]triazolo[4,3-a]pyridin-6-yl, imidazo[1,2- a]pyridin-6-yl, imidazo[1,2-a]pyridin-7-yl, imidazo[1,5-a]pyridin-6-yl, pyrazolo[4,3- b]pyridin-6-yl, 1H-pyrazolo[3,4-b]pyridin-5-yl, 1H-pyrazolo[3,4-b]pyridin-5-yl, 1H- pyrazolo[4,3-b]pyridin-5-yl, 1H-pyrazolo[4,3-b]pyridin-6-yl, 1H-thieno[2,3-c]pyrazol-5-yl, 1H-thieno[3,2-c]pyrazol-5-yl and thiazolo[5,4-b]pyridin-6-yl), each optionally substituted (e.g., substituted at available positions with 0, 1, 2 or 3 instances of R ³ , wherein each R ³ is as defined in any of the embodiments described herein). [0280] In some embodiments, Ring B is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetan-3-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, pyrazol-5-yl, thiophen-3-yl, oxazol-5-yl, thiazol- 5-yl, pyridin-3-yl, pyridin-4-yl, phenyl, naphthalen-1-yl, naphthalen-2-yl, indol-4-yl, indol-5- yl, benzofuran-5-yl, benzofuran-6-yl, 1H indazol-5-yl, 1H indazol-4-yl, 2H-indazol-6-yl, 2H- indazol-5-yl, benzo[b]thiophen-3-yl, benzo[b]thiophen-5-yl, quinolin-6-yl, quinolin-7-yl, quinoline-3-yl, isoquinolin-6-yl, benzo[d]imidazo-5-yl, 1H-benzo[d]imidazol-4-yl, benzo[d]thiazol-5-yl, benzo[d]thiazol-6-yl, benzo[d]thiazol-4-yl, benzo[d]isothiazol-5-yl, benzo[d]oxazol-4-yl, benzo[d]oxazol-5-yl, [1,2,4]triazolo[4,3-a]pyridin-6-yl, imidazo[1,2- a]pyridin-6-yl, imidazo[1,2-a]pyridin-7-yl, imidazo[1,5-a]pyridin-6-yl, pyrazolo[4,3- b]pyridin-6-yl, 1H-pyrazolo[3,4-b]pyridin-5-yl, 1H-pyrazolo[3,4-b]pyridin-5-yl, 1H- pyrazolo[4,3-b]pyridin-5-yl, 1H-pyrazolo[4,3-b]pyridin-6-yl, 1H-thieno[2,3-c]pyrazol-5-yl, 1H-thieno[3,2-c]pyrazol-5-yl and thiazolo[5,4-b]pyridin-6-yl), each optionally substituted (e.g., substituted at available positions with 0, 1, 2 or 3 instances of R ³ , wherein each R ³ is as defined in any of the embodiments described herein). [0281] In yet some embodiments, Ring B is selected from the group consisting of cyclopentyl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, pyrazol-5-yl, pyrazol-3-yl, thiophen- 3-yl, oxazol-5-yl, pyridin-3-yl, pyridin-4-yl, phenyl, naphthalen-2-yl, 1H-indazol-5-yl, 2H- indazol-6-yl, 2H-indazol-5-yl, quinolin-6-yl, quinolin-7-yl, isoquinolin-6-yl, benzo[d]thiazol- 5-yl, each optionally substituted (e.g., substituted at available positions with 0, 1, 2 or 3 instances of R ³ , wherein each R ³ is as defined in any of the embodiments described herein). [0282] In yet some embodiments, Ring B is selected from the group consisting of cyclopentyl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, pyrazol-5-yl, thiophen-3-yl, oxazol- 5-yl, pyridin-3-yl, pyridin-4-yl, phenyl, naphthalen-2-yl, 2H-indazol-6-yl, 2H-indazol-5-yl, quinolin-6-yl, quinolin-7-yl, isoquinolin-6-yl, benzo[d]thiazol-5-yl, each optionally substituted (e.g., substituted at available positions with 0, 1, 2 or 3 instances of R ³ , wherein each R ³ is as defined in any of the embodiments described herein). [0283] In some embodiments, Ring B is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuran-3-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, pyrazol-5-yl, pyrazol-3-yl, thiophen-3-yl, oxazol- 5-yl, pyridin-3-yl, pyridin-4-yl, phenyl, naphthalen-2-yl, 1H indazol-5-yl, 1H indazol-4-yl, 2H-indazol-6-yl, 2H-indazol-5-yl, quinolin-6-yl, quinolin-7-yl, isoquinolin-6-yl, 1,2,3,4- tetrahydroquinolin-6-yl, 1,2,3,4-tetrahydroisoquinolin-6-yl, 1,2,3,4-tetrahydroisoquinolin-7- yl, 2,3-dihydrobenzofuran-4-yl, 2,3-dihydrobenzofuran-5-yl, 2,3-dihydrobenzofuran-7-yl and benzo[d]thiazol-5-yl, each optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0284] In some embodiments, Ring B is unsubstituted. In some embodiments, Ring B is substituted with 1 instance of R ³ . In some embodiments, Ring B is substituted with 2 instances of R ³ . In some embodiments, Ring B is substituted with 3 instances of R ^3. . [0285] In some embodiments, Ring B is –C ₃ –C ₁₀ carbocyclyl. In some embodiments, the carbocyclyl is not further substituted. In some embodiments, the carbocyclyl is substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as described herein. In some embodiments, the carbocyclyl is substituted with 1 or 2 instances of halo (e.g., –F, –Cl), –Me, –Et, –iPr, – OH, =O or –CN. In some embodiments, the carbocyclyl is a –C ₃ –C ₁₀ mono or bicyclic cycloalkyl (e.g., a monocyclic cycloalkyl, a fused bicyclic cycloalkyl, a spiro cycloalkyl or a bridged cycloalkyl). In some embodiments, the carbocyclyl is a –C ₃ –C ₇ monocyclic cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl). In some embodiments, Ring B is cyclopropyl. In some embodiments Ring B is cyclobutyl. In some embodiments, Ring B is cyclopentyl. In some embodiments, Ring B is cyclohexyl. In some embodiments, the carbocyclyl is a –C4–C ₁₀ bicyclic cycloalkyl. In some embodiments, Ring B is a –C4–C ₁₀ fused cycloalkyl (e.g., decahydronaphthyl, octahydroindenyl). In some embodiments, Ring B is a –C ₄ –C ₁₀ spiro cycloalkyl (e.g., spiro[4.5]decanyl, spiro[4.4]nonanyl, spiro[3.3]heptanyl, spiro[3.4]octanyl). [0286] In some embodiments, the carbocyclyl is a –C ₃ –C ₇ monocyclic carbocyclyl fused with phenyl (e.g., 1,2,3,4-tetrahydronaphthalenyl, 2,3-dihydro-1H-indenyl wherein the attachment point is on the saturated ring). In some embodiments, Ring B is a –C ₃ –C ₇ monocyclic carbocyclyl fused with a 5-6-membered heterocyclyl ring containing 1-3 atoms independently selected from the group consisting of N, O, S or oxidized forms thereof (e.g., octahydrochromenyl, decahydroisoquinolinyl, decahydroquinolinyl, octahydroindolyl, octahydroisoindolyl, hexahydro chromane, hexahydro isoquinoline, hexahydroquinoline, octahydrobenzofuran wherein the attachment point is on the carbocyclic ring). In some embodiments, Ring B is a –C ₃ –C ₇ monocyclic carbocyclyl fused with a 5-6-membered heteroaryl ring containing 1-3 atoms independently selected from the group consisting of N, O, S or oxidized forms thereof (e.g., 4,5,6,7-tetrahydro-1H-indazolyl). [0287] In some embodiments, Ring B is C ₃ -C ₇ monocyclic cycloalkyl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0288] In some embodiments, Ring B is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, each optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0289] In some embodiments, Ring B is cyclopropyl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0290] In some embodiments, Ring B is cyclobutyl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0291] In some embodiments, Ring B is cyclopentyl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0292] In some embodiments, Ring B is cyclohexyl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0293] In some embodiments, Ring B is selected from the group consisting of: wh ³ erein each R is independently as defined in any of the embodiments described herein. [0294] In some embodiments, Ring B is a 3-10 membered mono or bicyclic heterocyclyl. In some embodiments, Ring B is a 3-8 membered monocyclic heterocyclyl containing 1-3 heteroatoms selected from the group consisting of N, O and S or oxidized forms thereof (e.g., oxetanyl, tetrahydropyranyl, tetrahydrofuranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl, tetrahydropyridinyl). In some embodiments, ring B is oxetanyl (e.g., oxetan-3-yl). In some embodiments, Ring B is selected from the group consisting of tetrahydrofuranyl and tetrahydropyranyl, each optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0295] In some embodiments, Ring B is selected from the group consisting of tetrahydrofuran-3-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl and tetrahydropyran-4-yl, each optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0296] In some embodiments, ring B is tetrahydrofuranyl (e.g., tetrahydrofuran-2-yl, tetrahydrofuran-3-yl). In some embodiments, Ring B is tetrahydrofuran-3-yl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0297] In some embodiments, ring B is tetrahydropyranyl (e.g., tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl). In some embodiments, Ring B is tetrahydropyran-2-yl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0298] In some embodiments, Ring B is tetrahydropyran-3-yl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0299] In some embodiments, Ring B is tetrahydropyran-4-yl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0300] n some embodiments, Ring B is selected from the group consisting of: [0301] In some embodiments, Ring B is In some embodiments, Ring B is In some embodiments, Ring B is In some embodiments, Ring B is [0302] In some embodiments, ring B is azetidinyl (e.g., azetidin-3-yl). In some embodiments, ring B is pyrrolidinyl (e.g., pyrrolidin-2-yl, pyrrolidin-3-yl). In some embodiments, ring B is piperidinyl (e.g., piperidin-2-yl, piperidin-3-yl, piperidin-4-yl). In some embodiments, ring B is piperazinyl (e.g., piperazin-4-yl). In some embodiments, ring B is morpholinyl. In some embodiments, ring B is tetrahydropyridinyl. In some embodiments, Ring B is azepanyl. [0303] In some embodiments, Ring B is a 4-10 membered bicyclic heterocyclyl containing 1-3 heteroatoms independently selected from the group consisting of N, O and S or oxidized forms thereof. In some embodiments, the mono or bicyclic heterocyclyl is not further substituted. In some embodiments, the heterocyclyl is substituted with 1 or 2 instances of halo (e.g., –F, –Cl), –Me, –Et, –iPr, –OH, =O or –CN. In some instances, the heterocyclyl is substituted with =O (e.g., 2-oxo-1,2-dihydropyridin-4-yl). [0304] In some embodiments, Ring B is an optionally substituted 6-10 membered mono or bicyclic aryl (i.e., a C ₆ -C ₁₀ aryl, e.g., naphthalenyl, phenyl, 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, 2,3-dihydrobenzofuranyl). In some embodiments, Ring B is substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as described herein. In some embodiments, Ring B is selected from the group consisting of naphthalenyl, phenyl, 1,2,3,4- tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl and 2,3-dihydrobenzofuranyl, each optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0305] In some embodiments, Ring B is selected from the group consisting of naphthalenyl, phenyl, 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl and 2,3- dihydrobenzofuranyl, each optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0306] In some embodiments, Ring B is selected from the group consisting of phenyl, naphthalen-2-yl, 1,2,3,4-tetrahydroquinolin-6-yl, 1,2,3,4-tetrahydroisoquinolin-6-yl, 1,2,3,4- tetrahydroisoquinolin-7-yl, 2,3-dihydrobenzofuran-4-yl, 2,3-dihydrobenzofuran-5-yl and 2,3- dihydrobenzofuran-7-yl, each optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0307] In some embodiments, Ring B is naphthalenyl or phenyl, each optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein).In some embodiments, Ring B is optionally substituted phenyl. In some embodiments, Ring B is phenyl substituted with 0, 1, 2 or 3 instances of R ³ , wherein each R ³ is independently as described herein. In some embodiments, the phenyl is unsubstituted. In some embodiments, the phenyl is substituted with one instance of R ³ . In some embodiments, the phenyl is substituted with 1 instance of R ³ at the position para- to the attachment point to the piperidine. In some embodiments, the phenyl is substituted with 1 instance of R ³ at the position meta- to the attachment point to the piperidine. In some embodiments, the phenyl is substituted with 2 instances of R ³ . In some embodiments, the phenyl is substituted with 3 instances of R ³ . [0308] In some embodiments, Ring B is selected from the group consisting of: wherein each R ³ is independently as defined in any of the embodiments described herein. [0309] In some embodiments, Ring B is selected from the group consisting of: wherein each R ³ is as defined in any of the embodiments described herein. [0310] In some embodiments, Ring B is selected from the group consisting of: wherein each R ³ is as defined in any of the embodiments described herein. [0311] In some embodiments, Ring B is: . In some embodiments, Ring B is wherein each R ³ is as defined in any of the embodiments described herein. In some embodiments, Ring B is:

[0312] In some embodiments, the compounds of Formula (I) are of Formula (III1): wher ^{1 2} ein Ring A, R , R and n are as defined in any of the embodiments described herein and the phenyl is substituted with 0, 1, 2 or 3 instances of R ³ as defined in any of the embodiments described herein. In some embodiments, the compounds of Formula (I) are of Formula (III1a): wherein Ring A, R ¹ , R ² and n are as defined in any of the embodiments described herein and the phenyl is substituted with 0, 1, 2 or 3 instances of R ³ as defined in any of the embodiments described herein. In yet some embodiments, compounds of Formula (I) are of Formula (III1b), wherein Ring A, R ¹ , R ² R ³ and n are as defined in any of the embodiments described herein. [0313] In other embodiments, compounds of Formula (I) are of Formula (III1c), wherein Ring A, R ¹ , R ^{2 3} R and n are as defined in any of the embodiments described herein. [0314] In certain embodiments, compounds of Formula (I) are of Formula (III1d), wherein Ring A, R ¹ , R ² R ³ and n are as defined in any of the embodiments described herein [0315] In some embodiments, Ring B is phenyl substituted with halo (e.g., fluoro, chloro, bromo), –CN or –CF ₃ . In some embodiments, Ring B is phenyl substituted with halo (e.g., fluoro, chloro, bromo). In some embodiments, Ring B is phenyl substituted with –CN. In some embodiments, Ring B is phenyl substituted with –CF ₃ . . [0316] In some embodiments, Ring B is an optionally substituted 9-10 membered bicyclic aryl (e.g., naphthalenyl). In some embodiments, Ring B is naphthalenyl (e.g., naphthalen-1- yl, naphthalen-2-yl). In some embodiments, Ring B is naphthalen-2-yl. In some embodiments, Ring B is an optionally substituted bicyclic aryl containing a phenyl ring fused with a C ₅ -C ₆ carbocycle (e.g., tetrahydronaphthyl, dihydroindenyl). In some embodiments, Ring B is 1,2,3,4-tetrahydronaphthalenyl. In some embodiments, Ring B is 2,3-dihydro-1H- indenyl. In some embodiments, Ring B is an optionally substituted bicyclic aryl containing a phenyl ring fused with a 5-6 membered heterocycle containing 1-3 heteroatoms independently selected from the group consisting of N, O and S or oxidized forms thereof (e.g., 1,2,3,4 tetrahydroquinolinyl, 1,2 dihydroquinolinyl, 1,2-dihydroisoquinolinyl, tetrahydroisoquinolinyl, chromanyl, indolinyl, isoindolinyl, dihydrobenzoxazinyl, dihydrobenzofuranyl, benzodioxolyl, dihydrobenzimidazolyl). In some embodiments, Ring B is selected from the group consisting of 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4- tetrahydroisoquinolinyl and 2,3-dihydrobenzofuranyl, each optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0317] In some embodiments, Ring B is selected from the group consisting of 1,2,3,4- tetrahydroquinolin-6-yl, 1,2,3,4-tetrahydroisoquinolin-6-yl, 1,2,3,4-tetrahydroisoquinolin-7- yl, 2,3-dihydrobenzofuran-4-yl, 2,3-dihydrobenzofuran-5-yl and 2,3-dihydrobenzofuran-7-yl, each optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0318] In some embodiments, Ring B is 1,2,3,4-tetrahydroquinolinyl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0319] In some embodiments, Ring B is 1,2,3,4-tetrahydroquinolin-6-yl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0320] In some embodiments, Ring B is 1,2,3,4-tetrahydroisoquinolinyl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0321] In some embodiments, Ring B is 1,2,3,4-tetrahydroisoquinolin-6-yl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0322] In some embodiments, Ring B is 1,2,3,4-tetrahydroisoquinolin-7-yl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0323] In some embodiments, Ring B is 2,3-dihydrobenzofuranyl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0324] In some embodiments, Ring B is 2,3-dihydrobenzofuran-4-yl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0325] In some embodiments, Ring B is 2,3-dihydrobenzofuran-5-yl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0326] In some embodiments, Ring B is 2,3-dihydrobenzofuran-7-yl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0327] In some embodiments, the bicyclic aryl is unsubstituted. In some embodiments, Ring B is unsubstituted naphthalenyl (e.g., naphthalen-1-yl, naphthalen-2-yl). In some embodiments, Ring B is unsubstituted naphthalen-2-yl. In some embodiments, the bicyclic aryl is substituted with 0, 1, 2 or 3 instances of R ³ , wherein each R ³ is as described herein. In some embodiments, the bicyclic aryl is substituted with 1 instance of R ³ . In some embodiments, the bicyclic aryl is substituted with one instance of R ³ wherein R ³ is selected from the group consisting of halo (e.g., –F, –Cl, Br), –Me, =O. [0328] In some embodiments, Ring B is selected from the group consisting of: R wherein each R ³ is independently as defined in any of the embodiments described herein. [0329] In some embodiments, Ring B is selected from the group consisting of: wherein ³ each R is independently as defined in any of the embodiments described herein. [0330] In some embodiments, Ring B is _{In some embodiments, Ring B is} wherein R ³ is as defined in any of the embodiments described herein. In some embodiments, Ring B is ³ wherein R is as defined in any of the embodiments

[0331] In some embodiments, Ring B is an optionally substituted 5-6 membered monocyclic heteroaryl (e.g., a 5-membered monocyclic heteroaryl containing 1-3 heteroatoms independently selected from the group consisting of O, N and S, a 6-membered monocyclic heteroaryl containing 1-3 N heteroatoms). [0332] In some embodiments, the 5-6 membered monocyclic heteroaryl is unsubstituted. In some embodiments, the 5-6 membered monocyclic heteroaryl is substituted with 0, 1, 2 or 3 instances of R ³ , wherein each R ³ is as described herein. In some embodiments, the 5-6 membered monocyclic heteroaryl is substituted with 1 instance of R ³ . In some embodiments, the 5-6 membered monocyclic heteroaryl is substituted with 2 instances of R ³ . In some embodiments, the 5-6 membered monocyclic heteroaryl is substituted with 2 instances of R ³ . In some embodiments, the 5-6 membered monocyclic heteroaryl is substituted with 3 instances of R ³ . [0333] In some embodiments, Ring B is selected from the group consisting of pyrazolyl, thiophenyl, oxazolyl and pyridinyl, each optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0334] In some embodiments, Ring B is a 5-membered monocyclic heteroaryl (e.g., pyrazolyl, pyrrolyl, thiophenyl, furyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, triazolyl, thiadiazolyl, oxadiazolyl). In some embodiments, Ring B is selected from the group consisting of pyrazolyl, thiophenyl and oxazolyl, each optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0335] In some embodiments, Ring B is pyrazolyl (e.g., pyrazol-3-yl, pyrazol-4-yl, pyrazol- 5-yl). In some embodiments, Ring B is pyrrolyl (e.g., pyrrol-1-yl, pyrrol-2-yl, pyrrol-3-yl). In some embodiments, Ring B is thiophenyl (e.g., thiophen-2-yl, thiophen-3-yl). In some embodiments, Ring B is furyl (e.g., fur-2-yl, fur-3-yl). In some embodiments, Ring B is thiazolyl (e.g., thiazol-2-yl, thiazol-4-yl, thiazol-5-yl). In some embodiments, Ring B is isothiazolyl (e.g., isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl). In some embodiments, Ring B is oxazolyl (e.g., oxazol-2-yl, oxazol-4-yl, oxazol-5-yl). In some embodiments, Ring B is isoxazolyl (e.g., isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl). In some embodiments, Ring B is imidazolyl (e.g., imidazol-2-yl, imidazol-4-yl). In some embodiments, Ring B is triazolyl. In some embodiments, Ring B is thiadiazolyl. In some embodiments, Ring B is oxadiazolyl. In some embodiments, Ring B is pyrazol-5-yl. In some embodiments, Ring B is pyrazol-3-yl. In some embodiments, Ring B is thiophen-3-yl. In some embodiments, Ring B is oxazol-5-yl. [0336] In certain embodiments, the 5-membered monocyclic heteroaryl is unsubstituted. In some embodiments, the 5-membered monocyclic heteroaryl is substituted with 1 instance of R ³ . In some embodiments, the 5-membered monocyclic heteroaryl is substituted with 2 instances of R ³ . In some embodiments, the 5-membered monocyclic heteroaryl is substituted with 3 instances of R ³ . [0337] In some embodiments, Ring B is a 6-membered monocyclic heteroaryl (e.g., pyridyl, pyrimidinyl, triazinyl, pyrazinyl, pyridazinyl). In some embodiments, the 6-membered monocyclic heteroaryl is unsubstituted. In some embodiments, the 6-membered monocyclic heteroaryl is substituted with 0, 1, 2 or 3 instances of R ³ . In some embodiments, the 6- membered monocyclic heteroaryl is substituted with 1 instance of R ³ . In some embodiments, the 6-membered monocyclic heteroaryl is substituted with 2 instances of R ³ . In some embodiments, the 6-membered monocyclic heteroaryl is substituted with 3 instances of R ³ . In some embodiments, Ring B is pyridinyl (e.g., pyridin-2-yl, pyridin-3-yl, pyridin-4-yl). In some embodiments, Ring B is pyridin-2-yl. In some embodiments, Ring B is pyridin-3-yl. In some embodiments, Ring B is pyridin-4-yl. In some embodiments, Ring B is pyrimidinyl (e.g, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl). [0338] In some embodiments, Ring B is selected from the group consisting of:

wherein R ³ is as defined in any of the embodiments described herein. [0340] In some embodiments, Ring B is an 8-10 membered bicyclic heteroaryl, wherein the bicyclic heteroaryl is optionally substituted (e.g., substituted with 0, 1, 2 or 3 instances of R ³ wherein R ³ is as defined in any of the embodiments described herein). In certain embodiments, Ring B is an 8-10 membered bicyclic heteroaryl (e.g., a 5,5 bicyclic heteroaryl (e.g., 1H-thieno[2,3-c]pyrazolyl, 1H-thieno[3,2-c]pyrazolyl), a 5,6 bicyclic heteroaryl (e.g., indolyl, benzofuranyl, 1H-indazolyl, 2H-indazolyl, benzo[b]thiophenyl, benzo[d]imidazolyl, benzo[d]thiazolyl, benzo[d]oxazolyl, [1,2,4]triazolo[4,3-a]pyridinyl, benzo[d]isothiazolyl, imidazo[1,2-a]pyridinyl, imidazo[1,2-a]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl),1H- pyrazolo[3,4-b]pyridinyl, thiazolo[5,4-b]pyridinyl), or a 6, 6 bicyclic heteroaryl (e.g., quinolinyl, 1,5-naphthyridinyl, 1,2-dihydro-1,5-naphthyridinyl, 1,2,3,4-tetrahydro-1,8- naphthyridinyl, isoquinolinyl),wherein each bicyclic heteroaryl contains 1, 2, 3 or 4 heteroatoms independently selected from the group consisting of O, N and S, and wherein each bicyclic heteroaryl is optionally substituted (e.g., substituted with 0, 1, 2 or 3 instances of R ³ wherein R ³ is as defined in any of the embodiments described herein). In some embodiments, Ring B is a 5,6 bicyclic heteroaryl (e.g., indolyl, benzofuranyl, 1H-indazolyl, 2H-indazolyl, benzo[b]thiophenyl, benzo[d]imidazolyl, benzo[d]thiazolyl, benzo[d]oxazolyl, [1,2,4]triazolo[4,3-a]pyridinyl, benzo[d]isothiazolyl, imidazo[1,2-a]pyridinyl, imidazo[1,2- a]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl),1H- pyrazolo[3,4-b]pyridinyl, thiazolo[5,4- b]pyridinyl) or a 6,6 bicyclic heteroaryl (e.g., quinolinyl, isoquinolinyl, 1,5-naphthyridinyl, 1,2-dihydro-1,5-naphthyridinyl, 1,2,3,4-tetrahydro-1,8-naphthyridinyl, isoquinolinyl). [0341] In some embodiments, Ring B is a 5,6 bicyclic heteroaryl (e.g., indolyl, benzofuranyl, 1H-indazolyl, 2H-indazolyl, benzo[b]thiophenyl, benzo[d]imidazolyl, benzo[d]thiazolyl, benzo[d]oxazolyl, [1,2,4]triazolo[4,3-a]pyridinyl, benzo[d]isothiazolyl, imidazo[1,2-a]pyridinyl, imidazo[1,2-a]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl),1H- pyrazolo[3,4-b]pyridinyl, thiazolo[5,4-b]pyridinyl). [0342] In some embodiments, ring B is a 6,6 bicyclic heteroaryl (e.g., quinolinyl, isoquinolinyl, 1,5-naphthyridinyl, 1,2-dihydro-1,5-naphthyridinyl, 1,2,3,4-tetrahydro-1,8- naphthyridinyl, isoquinolinyl) [0343] In some embodiments, the bicyclic heteroaryl (e.g., the 5,5 bicyclic heteroaryl, 5,6 bicyclic heteroaryl, 6,6 bicyclic heteroaryl) contains 1, 2 or 3 heteroatoms selected from the group consisting of O, N and S. In some embodiments, the bicyclic heteroaryl contains 1 or 2 heteroatoms selected from the group consisting of O, N and S. In some embodiments, the bicyclic heteroaryl contains 1 heteroatom selected from the group consisting of O, N and S. In some embodiments, the bicyclic heteroaryl contains 2 heteroatoms selected from the group consisting of O, N and S. In some embodiments, the bicyclic heteroaryl contains 3 heteroatoms selected from the group consisting of O, N and S. In some embodiments, the bicyclic heteroaryl contains 4 heteroatoms selected from the group consisting of O, N and S. [0344] In some embodiments Ring B is selected from the group consisting of indolyl, benzofuranyl, 1H-indazolyl, 2H-indazolyl, benzo[b]thiophenyl, quinolinyl, 1,5- naphthyridinyl, 1,2-dihydro-1,5-naphthyridinyl, 1,2,3,4-tetrahydro-1,8-naphthyridinyl, imidazo[1,2-a]pyridinyl, imidazo[1,5-a]pyridinyl, isoquinolinyl, benzo[d]imidazolyl, benzo[d]thiazolyl, benzo[d]isothiazolyl, benzo[d]oxazolyl, [1,2,4]triazolo[4,3-a]pyridinyl, imidazo[1,2-a]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl),1H- pyrazolo[3,4-b]pyridinyl, 1H- thieno[2,3-c]pyrazolyl, 1H-thieno[3,2-c]pyrazolyl, thiazolo[5,4-b]pyridinyl and 1,2,3,4- tetrahydro-1,8-naphthyridinyl, each optionally substituted (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). [0345] In certain embodiments, Ring B is selected from the group consisting of 1H- indazolyl, 2H-indazolyl, quinolinyl, isoquinolinyl and benzo[d]thiazolyl, each optionally substituted (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). [0346] In certain embodiments, Ring B is selected from the group consisting of 2H- indazolyl, quinolinyl, isoquinolinyl and benzo[d]thiazolyl, each optionally substituted (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). In some embodiments, Ring B is 1H indazolyl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0347] In some embodiments, Ring B is 2H-indazolyl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0348] In some embodiments, Ring B is quinolinyl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0349] In some embodiments, Ring B is isoquinolinyl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0350] In some embodiments, Ring B is and benzo[d]thiazolyl, optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0351] In some embodiments, Ring B is selected from the group consisting of indol-4-yl, indol-5-yl, benzofuran-5-yl, benzofuran-6-yl, 1H indazol-5-yl, 1H indazol-4-yl, 2H-indazol- 6-yl, 2H-indazol-5-yl, benzo[b]thiophen-3-yl, benzo[b]thiophen-5-yl, quinolin-6-yl, quinolin- 7-yl, quinoline-3-yl, isoquinolin-6-yl, benzo[d]imidazo-5-yl, 1H-benzo[d]imidazol-4-yl, benzo[d]thiazol-5-yl, benzo[d]thiazol-6-yl, benzo[d]thiazol-4-yl, benzo[d]isothiazol-5-yl, benzo[d]oxazol-4-yl, benzo[d]oxazol-5-yl, [1,2,4]triazolo[4,3-a]pyridin-6-yl, imidazo[1,2- a]pyridin-6-yl, imidazo[1,2-a]pyridin-7-yl, imidazo[1,5-a]pyridin-6-yl, pyrazolo[4,3- b]pyridin-6-yl, 1H-pyrazolo[3,4-b]pyridin-5-yl, 1H-pyrazolo[3,4-b]pyridin-5-yl, 1H- pyrazolo[4,3-b]pyridin-5-yl, 1H-pyrazolo[4,3-b]pyridin-6-yl, 1H-thieno[2,3-c]pyrazol-5-yl, 1H-thieno[3,2-c]pyrazol-5-yl and thiazolo[5,4-b]pyridin-6-yl, each optionally substituted (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). [0352] In some embodiments, Ring B is independently selected from the group consisting of 1H-indazol-5-yl, 1H indazol-4-yl, 2H-indazol-6-yl, 2H-indazol-5-yl, quinolin-6-yl, quinolin-7-yl, isoquinolin-6-yl and benzo[d]thiazol-5-yl, each optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ³ , wherein R ³ is as defined in any of the embodiments described herein). [0353] In some embodiments, Ring B is independently selected from the group consisting of 1H-indazol-5-yl, 2H-indazol-6-yl, 2H-indazol-5-yl, quinolin-6-yl, quinolin-7-yl, isoquinolin-6-yl and benzo[d]thiazol-5-yl, each optionally substituted (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). In some embodiments, Ring B is optionally substituted 2H- indazol-6-yl (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). In some embodiments, Ring B is independently selected from the group consisting of 2H-indazol-6-yl, 2H-indazol-5-yl, quinolin-6-yl, quinolin-7-yl, isoquinolin-6-yl and benzo[d]thiazol-5-yl, each optionally substituted (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). In some embodiments, Ring B is optionally substituted 1H-indazol-5-yl (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). In some embodiments, Ring B is optionally substituted 1H indazol-4-yl (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). [0354] In some embodiments, Ring B is optionally substituted 2H-indazol-6-yl (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). In some embodiments, Ring B is optionally substituted 2H-indazol-5-yl (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). In some embodiments, Ring B is optionally substituted quinolin-6-yl (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). In some embodiments, Ring B is optionally substituted quinolin-7-yl (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). In some embodiments, Ring B is optionally substituted isoquinolin-6-yl (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). In some embodiments, Ring B is optionally substituted benzo[d]thiazol-5-yl (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). [0355] In some embodiments Ring B is an 8-10 membered bicyclic heteroaryl selected from the group consisting of:

, each optionally substituted (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). [0356] In certain embodiments, Ring B is selected from the group consisting of: each optionally substituted (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). [0357] In certain embodiments, Ring B is selected from the group consisting of: each optionally substituted (e.g., substituted with 0, 1, 2 or 3 instances of R ³ ). [0358] In some embodiments, the 8-10 membered bicyclic heteroaryl is unsubstituted. In some embodiments, the 8-10 membered bicyclic heteroaryl is substituted with 1 instance of R ³ . In some embodiments, the 8-10 membered bicyclic heteroaryl is substituted with 2 instances of R ³ . In some embodiments, 8-10 membered bicyclic heteroaryl is substituted with 3 instances of R ³ . [0359] In some embodiments, Ring B is selected from the group consisting of: wherein each R ³ is independently as defined in any of the embodiments described herein. [0360] In certain embodiments, Ring B is selected from the group consisting of: wherein R ³ is as defined in any of the embodiments described herein. [0361] In certain embodiments, Ring B is selected from the group consisting of: wherein R ³ is as defined in any of the embodiments described herein. [0362] In some embodiments, Ring B is selected from the group consisting of: Ring B is selected from the group consisting of: and wherein R3 is as defined in any of the embodiments described herein. In some embodiments, Ring B is selected from the group consisting of: wherein R ³ is as defined in any of the embodiments described herein. [0363] In some embodiments, Ring B is selected from the group consisting of: wherein R ³ is as defined in any of the embodiments described herein. [0364] In certain embodiments, Ring B is selected from the group consisting of: whe ³ rein R is as defined in any of the embodiments described herein. [0365] In some embodiments, Ring B is selected from the group consisting of: where ³ in R is as defined in any of the embodiments described herein. [0366] In some embodiments, Ring B is wherein R ³ is as defined in any of the

[0367] In certain embodiments, Ring B is ³ wherein R is as defined in any of the embodiments described herein. In some embodiments, Ring B is wherein R ³ is as defined in any of the embodiments described herein. In other embodiments, Ring B is . [0368] In certain embodiments, Ring B is ³ wherein R is as defined in any of the embodiments described herein. [0369] In certain embodiments, Ring B is [0370] In certain embodiments, Ring B is wher ³ ein R is as defined in any of the embodiments described herein. [0371] In certain embodiments, Ring B is ³ wherein R is as defined in any of the embodiments described herein. [0372] In certain embodiments, Ring B is [0373] In certain embodiments, Ring B is ³ wherein R is as defined in any of the embodiments described herein. [0374] In some embodiments, the compounds of Formula (I) are of Formula (III2): wherein Ring A, R ¹ , R ² and n are as defined in any of the embodiments described herein and the 2H indazole is substituted with 0, 1, 2 or 3 instances of R ³ as defined in any of the embodiments described herein. In some embodiments, the compounds of Formula (I) are of Formula (III2)a: wherein Ring A, R ¹ , R ² and n are as defined in any of the embodiments described herein and the 2H indazole is substituted with 0, 1, 2 or 3 instances of R ³ as defined in any of the embodiments described herein. In yet some embodiments, compounds of Formula (I) are of Formula (III2b),

wherein Ring A, R ¹ , R ² R ³ and n are as defined in any of the embodiments described herein. [0375] In some embodiments, the compounds of Formula (I) are of Formula (III3): wherein R ^{1 2} ing A, R , R and n are as defined in any of the embodiments described herein and the 2H indazole is substituted with 0, 1, 2 or 3 instances of R ³ as defined in any of the embodiments described herein. In some embodiments, the compounds of Formula (I) are of Formula (III3a): wherein Ring A, R ¹ , R ² and n are as defined in any of the embodiments described herein and the 2H indazole is substituted with 0, 1, 2 or 3 instances of R ³ as defined in any of the embodiments described herein. In yet some embodiments, compounds of Formula (I) are of Formula (III3b), wherein Ring A, R ¹ , R ² R ³ and n are as defined in any of the embodiments described herein.

[0376] In some embodiments, the compounds of Formula (I) are of Formula (III4): wherein Ring A, R ¹ , R ² and n are as defined in any of the embodiments described herein and the benzothiazole is substituted with 0, 1, 2 or 3 instances of R ³ as defined in any of the embodiments described herein. In some embodiments, the compounds of Formula (I) are of Formula (III4a): wherein Ring A, R ¹ , R ² and n are as defined in any of the embodiments described herein and the benzothiazole is substituted with 0, 1, 2 or 3 instances of R ³ as defined in any of the embodiments described herein. In yet some embodiments, compounds of Formula (I) are of

Formula (III4b),

wherein Ring A, R ¹ , R ² R ³ and n are as defined in any of the embodiments described herein. [0377] In some embodiments, the compounds of Formula (I) are of Formula (III4c): wherein Ring A, R ¹ , R ² and n are as defined in any of the embodiments described herein and the benzothiazole is unsubstituted. [0378] In some embodiments, the compounds of Formula (I) are of Formula (III5): wherein Ring A, R ¹ , R ² and n are as defined in any of the embodiments described herein and the quinoline is substituted with 0, 1, 2 or 3 instances of R ³ as defined in any of the embodiments described herein. In some embodiments, the compounds of Formula (I) are of Formula (III5a): wherein Ring A, R ¹ , R ² and n are as defined in any of the embodiments described herein and the quinoline is substituted with 0, 1, 2 or 3 instances of R ³ as defined in any of the embodiments described herein. In yet some embodiments, compounds of Formula (I) are of Formula (III5b), wherein Ring A, R ¹ , R ² R ³ and n are as defined in any of the embodiments described herein.

[0379] In some embodiments, the compounds of Formula (I) are of Formula (III6): wherein Ring A, R ¹ , R ² and n are as defined in any of the embodiments described herein and the quinoline is substituted with 0, 1, 2 or 3 instances of R ³ as defined in any of the embodiments described herein. In some embodiments, the compounds of Formula (I) are of Formula (III6a): wherein Ring A, R ¹ , R ² and n are as defined in any of the embodiments described herein and the quinoline is substituted with 0, 1, 2 or 3 instances of R ³ as defined in any of the embodiments described herein. In yet some embodiments, the quinoline is unsubstituted. [0380] In some embodiments, the compounds of Formula (I) are of Formula (III7): (III7), wherein Ring A, R ¹ , R ² and n are as defined in any of the embodiments described herein and the isoquinoline is substituted with 0, 1, 2 or 3 instances of R ³ as defined in any of the embodiments described herein. In some embodiments, the compounds of Formula (I) are of Formula (III7a): wherein Ring A, R ¹ , R ² and n are as defined in any of the embodiments described herein and the isoquinoline is substituted with 0, 1, 2 or 3 instances of R ³ as defined in any of the embodiments described herein. In yet some embodiments, the isoquinoline is unsubstituted. [0381] As generally defined herein, each R ¹ is independently absent or selected from the group consisting of H, –D, halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, – C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, 5-6-membered monocyclic heteroaryl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a1 , –N(R ^a1 ) ₂ , –C(=O)R ^a1 , – C(=O)OR ^a1 , –NR ^a1 C(=O)R ^a1 , –NR ^a1 C(=O)OR ^a1 , –C(=O)N(R ^a1 ) ₂ , –OC(=O)N(R ^a1 ) ₂ , – S(=O)R ^a1 , –S(=O) ₂ R ^a1 , –SR ^a1 , –S(=O)(=NR ^a1 )R ^a1 , –NR ^a1 S(=O) ₂ R ^a1 and –S(=O) ₂ N(R ^a1 ) ₂ , wherein R ^a1 is as defined in any of the embodiments described herein. [0382] In some embodiments, each R ¹ is independently selected from the group consisting of H, halo (e.g., –F, –Cl), –CN, –C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr, –sec-Bu, – ^t Bu), 5- membered heteroaryl (e.g., pyrazolyl), –C ₁ –C ₆ haloalkyl (e.g., –CF ₃ , –CHF ₂ , –CH ₂ CF ₃ ), –C ₁ – C ₆ heteroalkyl (e.g., –CH ₂ OH), –C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl), –OR ^a1 (e.g., –OH, ––OCH ₃ , –OCHF ₂ ), –N(R ^a1 ) ₂ and – C(=O)N(R ^a1 ) ₂ (e.g., –C(=O)NH ₂ , –C(=O)NHCH ₃ ), wherein each R ^a1 is as defined in any of the embodiments described herein. In some embodiments, each R ^a1 is independently selected from the group consisting of H and –C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec- Bu, –iso-Bu). [0383] In some embodiments, each R ¹ is independently selected from the group consisting of H, –Me and –Et. [0384] In certain embodiments, each R ¹ is independently selected from the group consisting of H and methyl. [0385] In some embodiments, R ¹ is H. In some embodiments R ¹ is –D. [0386] In certain embodiments, R ¹ is halo (e.g., fluoro, chloro, bromo, iodo). In some embodiments, R ¹ is –Cl. In some embodiments, R ¹ is –F. In some embodiments, R ¹ is –Br. In some embodiments, R ¹ is –I. [0387] In some embodiments, R ¹ is –CN. [0388] In certain embodiments, R ¹ is –C ₁ –C ₆ alkyl. In some embodiments, R ¹ is selected from –Me and –Et. In some embodiments, R ¹ is –Me. In some embodiments, R ¹ is –Et. In some embodiments R ¹ is –Pr or –iPr. [0389] In some embodiments, R ¹ is –C ₁ –C ₆ heteroalkyl. In some embodiments, R ¹ is methoxymethyl (–CH ₂ OCH ₃ ). In some embodiments, R ¹ is hydroxymethyl (–CH ₂ OH). In some embodiments, R ¹ is aminomethyl (e.g.,–CH ₂ NH ₂ , –CH ₂ NHCH ₃ , –CH ₂ N(CH ₃ ) ₂ . [0390] In some embodiments, R ¹ is –C ₁ –C ₆ haloalkyl. In some embodiments, R ¹ is trifluoromethyl (–CF ₃ ). In other embodiments, R ¹ is difluoromethyl (–CHF ₂ ). [0391] In some embodiments, R ¹ is C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl). In some embodiments, R ¹ is cyclopropyl. In some embodiments R ¹ is cyclobutyl. In some embodiments, R ¹ is cyclopentyl. In some embodiments, R ¹ is cyclohexyl. [0392] In some embodiments, R ¹ is 3-10 membered heterocyclyl (e.g., oxetanyl, tetrahydropyranyl, tetrahydrofuranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl). In some embodiments, R ¹ is oxetanyl. In some embodiments, R ¹ is tetrahydropyranyl. In some embodiments, R ¹ is tetrahydrofuranyl. In some embodiments, R ¹ is azetidinyl. In some embodiments, R ¹ is pyrrolidinyl. In some embodiments, R ¹ is piperidinyl. In some embodiments, R ¹ is piperazinyl. In some embodiments, R ¹ is morpholinyl. In some embodiments, R ¹ is azepanyl. [0393] In some embodiments, R ¹ is a 5-6 membered monocyclic heteroaryl (e.g., a 5- membered monocyclic heteroaryl containing 1-3 heteroatoms independently selected from the group consisting of O, N and S, a 6-membered monocyclic heteroaryl containing 1-3 N heteroatoms). In some embodiments, R ¹ is a 5-membered monocyclic heteroaryl (e.g., pyrazolyl, pyrrolyl, thiophenyl, furyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, triazolyl, thiadiazolyl, oxadiazolyl). In some embodiments, R ¹ is thiophenyl (e.g., thiophen- 2-yl, thiophen-3-yl). In some embodiments, R ¹ is pyrazolyl (e.g., pyrazol-1-yl, pyrazol-3-yl, pyrazol-5-yl). In some embodiments, R ¹ is thiazolyl (e.g., thiazol-2-yl, thiazol-4-yl, thiazol- 5-yl). In some embodiments, R ¹ is a 6-membered monocyclic heteroaryl (e.g., pyridyl, pyrimidinyl, triazinyl, pyrazinyl, pyridazinyl). In some embodiments, R ¹ is pyridinyl (e.g., pyridin-2-yl, pyridin-3-yl, pyridin-4-yl). In some embodiments, R ¹ is pyrimidinyl (e.g, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl). [0394] In some embodiments R ¹ is cycloalkylalkyl (e.g., cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl). [0395] In some embodiments, R ¹ is heterocyclylalkyl (e.g., oxetanylmethyl, aziridinylmethyl, tetrahydrofuranylmethyl, pyrrolidinylmethyl, tetrahydropyranylmethyl, piperidinylmethyl, piperazinylmethyl, morpholinylmethyl, azepanylmethyl). [0396] In some embodiments, R ¹ is arylalkyl. In some embodiments, R ¹ is benzyl. [0397] In some embodiments, R ¹ is heteroarylalkyl (e.g., pyridinylmethyl, thiazolylmethyl, triazolylmethyl, pyrazolylmethyl). [0398] In some embodiments, R ¹ is –OR ^a1 wherein R ^a1 is as described herein (e.g., hydroxy (–OH), methoxy, difluoromethoxy (–OCHF ₂ ), trifluoromethoxy (–OCF ₃ ), ethoxy, propoxy, isopropoxy, cyclopropyloxy, cyclobutyloxy). In some embodiments, R ¹ is hydroxy. In some embodiments, R ¹ is methoxy. In some embodiments, R ¹ is ethoxy. In some embodiments, R ¹ is propoxy. In some embodiments, R ¹ is isopropoxy. In some embodiments R ¹ is difluoromethoxy. (–OCHF ₂ ). In some embodiments, R ¹ is trifluoromethoxy (–OCF ₃ ). [0399] In some embodiments, R ¹ is –N(R ^a1 ) ₂ (e.g., –NH ₂ , –NHR ^a1 , –N(CH ₃ )R ^a1 ). In some embodiments, R ¹ is –NH ₂ . In some embodiments, R ¹ is –NHR ^a1 (e.g., –NHCH ₃ , – NHCH ₂ CH ₃ , –NHPr, –NH ⁱ Pr, –NHcyclopropyl, –NHcyclobutyl). In some embodiments, R ¹ is –N(CH ₃ )R ^a1 (e.g., –N(CH ₃ ) ₂ , –N(CH ₃ )CH ₂ CH ₃ , –N(CH ₃ )CH ₂ CH ₂ CH ₃ , –N(CH ₃ ) ⁱ Pr, – N(CH ₃ )cyclopropyl, –N(CH ₃ )cyclobutyl). [0400] In some embodiments, R ¹ is –C(=O)R ^a1 or –C(=O)OR ^a1 wherein R ^a1 is as described herein. In some embodiments, R ¹ is –C(=O)R ^a1 wherein R ^a1 is as described herein. In some embodiments, R ¹ is –C(=O)alkyl. In some embodiments, R ¹ is –C(=O)CH ₃ , – C(=O)cyclopropyl, –C(=O)cyclobutyl, –C(=O) ^t Bu, –C(=O) ⁱ Pr, –C=(O)CH ₂ CH ₂ CH ₃ , or – C(=O)OCH ₃ . In some embodiments, R ¹ is acetyl (–C(=O)CH ₃ ). In some embodiments, R ¹ is –C(=O)OR ^a1 . In some embodiments, R ¹ is –COOH. In some embodiments, R ¹ is COOCH ₃ . [0401] In some embodiments, R ¹ is –NR ^a1 C(=O)R ^a1 wherein R ^a1 is as described herein. In certain embodiments, R ¹ is –NHC(=O)R ^a1 (e.g., –NHC(=O)CH ₃ , –NHC(=O)CH ₂ CH ₃ , – NHC(=O)CH ₂ CH ₂ CH ₃ , –NHC(=O) ⁱ Pr, –NHC(=O)Bu, –NHC(=O) ^t Bu, – NHC(=O)Cyclopropyl, –NHC(=O)Cyclobutyl). In some embodiments, R ¹ is – N(CH ₃ )C(=O)R ^a1 (e.g., –N(CH ₃ )C(=O)CH ₃ , –N(CH ₃ )C(=O)CH ₂ CH ₃ , – N(CH ₃ )C(=O)CH ₂ CH ₂ CH ₃ , –N(CH ₃ )C(=O) ⁱ Pr, –N(CH ₃ )C(=O)Bu, –N(CH ₃ )C(=O) ^t Bu, – N(CH ₃ )C(=O)Cyclopropyl, –N(CH ₃ )C(=O)Cyclobutyl). [0402] In some embodiments, R ¹ is –NR ^a1 C(=O)OR ^a1 wherein R ^a1 is as described herein. In certain embodiments, R ¹ is –NHC(=O)OR ^a1 (e.g., –NHC(=O)OCH ₃ , – NHC(=O)OCH ₂ CH ₃ , –NHC(=O)OCH ₂ CH ₂ CH ₃ , –NHC(=O)O ⁱ Pr, –NHC(=O)OBu, – NHC(=O)O ^t Bu, –NHC(=O)OCyclopropyl, –NHC(=O)OCyclobutyl). In some embodiments, R ¹ is –N(CH ₃ )C(=O)OR ^a1 (e.g., –N(CH ₃ )C(=O)OCH ₃ , –N(CH ₃ )C(=O)OCH ₂ CH ₃ , – N(CH ₃ )C(=O)OCH ₂ CH ₂ CH ₃ , –N(CH ₃ )C(=O)O ⁱ Pr, –N(CH ₃ )C(=O)OBu, – N(CH ₃ )C(=O)O ^t Bu, –N(CH ₃ )C(=O)OCyclopropyl, –N(CH ₃ )C(=O)OCyclobutyl). [0403] In some embodiments, R ¹ is –C(=O)N(R ^a1 ) ₂ (e.g., –C(=O)NH ₂ , –C(=O)NHR ^a1 , – C(=O)N(CH ₃ )R ^a1 ). In some embodiments, R ¹ is –C(=O)NH ₂ . In certain embodiments, R ¹ is –C(=O)NHR ^a1 (e.g., –C(=O)NHCH ₃ , –C(=O)NHCH ₂ CH ₃ , –C(=O)NHPr, –C(=O)NH ⁱ Pr, – C(=O)NHBu, –C(=O)NH ^t Bu, –C(=O)NHCyclopropyl, –C(=O)NHCyclobutyl). In certain embodiments, R ¹ is –C(=O)N(CH ₃ )R ^a1 (e.g., –C(=O)N(CH ₃ ) ₂ , –C(=O)N(CH ₃ )CH ₂ CH ₃ , – C(=O)N(CH ₃ )CH ₂ CH ₂ CH ₃ , –C(=O)N(CH ₃ ) ⁱ Pr, –C(=O)N(CH ₃ )Bu, –C(=O)N(CH ₃ ) ^t Bu, – C(=O)N(CH ₃ )Cyclopropyl, –C(=O)N(CH ₃ )Cyclobutyl). [0404] In some embodiments, R ¹ is –OC(=O)N(R ^a1 ) ₂ wherein R ^a1 is as described herein. In certain embodiments, R ¹ is –OC(=O)NHR ^a1 (e.g., –OC(=O)NHCH ₃ , –OC(=O)NHCH ₂ CH ₃ , – OC(=O)NHPr, –OC(=O)NH ⁱ Pr, –OC(=O)NHBu, –OC(=O)NH ^t Bu, – OC(=O)NHCyclopropyl, –OC(=O)NHCyclobutyl). In certain embodiments, R ¹ is – OC(=O)N(CH ₃ )R ^a1 (e.g., –OC(=O)N(CH ₃ ) ₂ , –OC(=O)N(CH ₃ )CH ₂ CH ₃ , – OC(=O)N(CH ₃ )CH ₂ CH ₂ CH ₃ , –OC(=O)N(CH ₃ ) ⁱ Pr, –OC(=O)N(CH ₃ )Bu, – OC(=O)N(CH ₃ ) ^t Bu, –OC(=O)N(CH ₃ )Cyclopropyl, –OC(=O)N(CH ₃ )Cyclobutyl). [0405] In some embodiments, R ¹ is –S(=O)R ^a1 wherein R ^a1 is as described herein. In certain embodiments, R ¹ is –S(=O)alkyl (e.g., –S(=O)CH ₃ , –S(=O)CH ₂ CH ₃ , – S(=O)CH ₂ CH ₂ CH ₃ , –S(=O) ⁱ Pr). In certain embodiments, R ¹ is –S(=O)cycloalkyl (e.g., – S(=O)cyclopropyl, –S(=O)cyclobutyl, –S(=O)cyclopentyl, –S(=O)cyclohexyl). [0406] In some embodiments, R ¹ is –S(=O) ₂ R ^a1 wherein R ^a1 is as described herein. In certain embodiments, R ¹ is –S(=O) ₂ alkyl (e.g., –S(=O) ₂ CH ₃ , –S(=O) ₂ CH ₂ CH ₃ , –S(=O) ₂ Pr, – S(=O) ₂ ⁱ Pr). In certain embodiments, R ¹ is –S(=O) ₂ cycloalkyl (e.g., –S(=O) ₂ cyclopropyl, – S(=O) ₂ cyclobutyl, –S(=O) ₂ cyclopentyl, –S(=O) ₂ cyclohexyl). In some embodiments, R ¹ is S(=O) ₂ aryl (e.g., –S(=O) ₂ phenyl). [0407] In some embodiments, R ¹ is –SR ^a1 wherein R ^a1 is as described herein. In certain embodiments, R ¹ is –Salkyl (e.g., –SCH ₃ , –SCH ₂ CH ₃ , –SPr, –S ⁱ Pr). In certain embodiments, R ¹ is –Scycloalkyl (e.g., –Scyclopropyl, –Scyclobutyl, –Scyclopentyl, –Scyclohexyl). In certain embodiments, R ¹ is –Saryl (e.g., –Sphenyl). [0408] In some embodiments, R ¹ is –S(=O)(=NR ^a1 )R ^a1 wherein R ^a1 is as described herein. In certain embodiments, R ¹ is –S(=O)(=NH)R ^a1 (e.g., –S(=O)(=NH)CH ₃ , – S(=O)(=NH)CH ₂ CH ₃ , –S(=O)(=NH)CH ₂ CH ₂ CH ₃ , –S(=O)(=NH) ⁱ Pr, –S(=O)(=NH)Bu, – S(=O)(=NH) ^t Bu, –S(=O)(=NH)Cyclopropyl, –S(=O)(=NH)Cyclobutyl). In some embodiments, R ¹ is –S(=O)(=NCH ₃ )R ^a1 (e.g., –S(=O)(=NCH ₃ )CH ₃ , – S(=O)(=NCH ₃ )CH ₂ CH ₃ , –S(=O)(=NCH ₃ )CH ₂ CH ₂ CH ₃ , –S(=O)(=NCH ₃ ) ⁱ Pr, – S(=O)(=NCH ₃ )Bu, –S(=O)(=NCH ₃ ) ^t Bu, –S(=O)(=NCH ₃ )Cyclopropyl, – S(=O)(=NCH ₃ )Cyclobutyl). [0409] In some embodiments, R ¹ is –NR ^a1 S(=O) ₂ R ^a1 wherein R ^a1 is as described herein. In certain embodiments, R ¹ is –NHS(=O) ₂ alkyl (e.g., –NHS(=O) ₂ CH ₃ , –NHS(=O) ₂ CH ₂ CH ₃ , – NHS(=O) ₂ Pr, –NHS(=O) ₂ ⁱ Pr). In certain embodiments, R ¹ is –NHS(=O) ₂ cycloalkyl (e.g., – NHS(=O) ₂ cyclopropyl, –NHS(=O) ₂ cyclobutyl, –NHS(=O) ₂ cyclopentyl, – NHS(=O) ₂ cyclohexyl). In certain embodiments, R ¹ is –N(CH ₃ )S(=O) ₂ alkyl (e.g., – N(CH ₃ )S(=O) ₂ CH ₃ , –N(CH ₃ )S(=O) ₂ CH ₂ CH ₃ , –N(CH ₃ )S(=O) ₂ Pr, –N(CH ₃ )S(=O) ₂ ⁱ Pr). In certain embodiments, R ¹ is –N(CH ₃ )S(=O) ₂ cycloalkyl (e.g., –N(CH ₃ )S(=O) ₂ cyclopropyl, – N(CH ₃ )S(=O) ₂ cyclobutyl, –N(CH ₃ )S(=O) ₂ cyclopentyl, –N(CH ₃ )S(=O) ₂ cyclohexyl). [0410] In some embodiments, R ¹ is –S(=O) ₂ N(R ^a1 ) ₂ wherein R ^a1 is as described herein. (e.g., –S(=O) ₂ NH ₂ , –S(=O) ₂ NHR ^a1 , –S(=O) ₂ N(CH ₃ )R ^a1 ). In some embodiments, R ¹ is – S(=O) ₂ NH ₂ . In some embodiments, R ¹ is –S(=O) ₂ NHR ^a1 (e.g., –S(=O) ₂ NHCH ₃ , – S(=O) ₂ NHCH ₂ CH ₃ , –S(=O) ₂ NHPr, –S(=O) ₂ NH ⁱ Pr, –S(=O) ₂ NHcyclopropyl, – S(=O) ₂ NHcyclobutyl). In some embodiments, R ¹ is –S(=O) ₂ N(CH ₃ )R ^a1 (e.g., – S(=O) ₂ N(CH ₃ ) ₂ , –S(=O) ₂ N(CH ₃ )CH ₂ CH ₃ , –S(=O) ₂ N(CH ₃ )CH ₂ CH ₂ CH ₃ , –S(=O) ₂ N(CH ₃ ) ⁱ Pr, –S(=O) ₂ N(CH ₃ )cyclopropyl, –S(=O) ₂ N(CH ₃ )cyclobutyl). [0411] As generally defined herein, each R ² is independently selected from the group consisting of –D, =O, halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ – C ₉ cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, –OR ^a2 , –N(R ^a2 ) ₂ , –C(=O)R ^a2 , –C(=O)OR ^a2 , –NR ^a2 C(=O)R ^a2 , – NR ^a2 C(=O)OR ^a2 , –CH ₂ C(=O)N(R ^a2 ) ₂ –C(=O)N(R ^a2 ) ₂ , –OC(=O)N(R ^a2 ) ₂ , –CH ₂ C(=O)N(R ^a2 ) ₂ , –S(=O)R ^a2 , –S(=O) ₂ R ^a2 , –SR ^a2 , –S(=O)(=NR ^a2 )R ^a2 , –NR ^a2 S(=O) ₂ R ^a2 and –S(=O) ₂ N(R ^a2 ) ₂ or two instances of R ² together with the atom or atoms to which they are attached can be taken together to form a 3-10 membered cycloalkyl or heterocyclyl ring (e.g., a ring that together with the piperidine ring of Formula (I) or Formula (A) can form a bridged, fused or spiro bicyclic heterocyclic ring), wherein R ^a2 is as defined in any of the embodiments described herein. [0412] In some embodiments of Formula A or Formula (I), two R ² groups are taken together with the atom to which they are attached to form a 3-10 membered spiro cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl) or spiro heterocyclyl ring (e.g., oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl, tetrahydrothiopyranyl, thiomorpholinyl). [0413] In some embodiments of Formula (A) or Formula (I), two R ² groups are taken together with the adjacent atoms to which they are attached to form a 3-10 membered fused cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl) or fused heterocyclyl ring (e.g., oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl, tetrahydrothiopyranyl, thiomorpholinyl). [0414] In some embodiments, the two R ² groups taken together with the atoms to which they are attached form a bridged piperidine-containing carbocyclyl or heterocyclyl ring (e.g., 2-azabicyclo[2.2.1]heptane, 2-azabicyclo[2.2.2]octane, 3-azabicyclo[3.2.1]octane). [0415] In other embodiments, the R ² groups are not taken together to form cycloalkyl or heterocyclyl rings (i.e., each R ² is independently selected from the group consisting of –D, =O, halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3- 10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, – OR ^a2 , –N(R ^a2 ) ₂ , –C(=O)R ^a2 , –C(=O)OR ^a2 , –NR ^a2 C(=O)R ^a2 , –NR ^a2 C(=O)OR ^a2 , – CH ₂ C(=O)N(R ^a2 ) ₂ –C(=O)N(R ^a2 ) ₂ , –OC(=O)N(R ^a2 ) ₂ , –CH ₂ C(=O)N(R ^a2 ) ₂ , –S(=O)R ^a2 , – S(=O) ₂ R ^a2 , –SR ^a2 , –S(=O)(=NR ^a2 )R ^a2 , –NR ^a2 S(=O) ₂ R ^a2 and –S(=O) ₂ N(R ^a2 ) ₂ , wherein R ^a2 is as defined in any of the embodiments described herein. [0416] In some embodiments, each R ² is independently selected from the group consisting of halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl), 3-6 membered heterocyclyl (e.g., oxetanyl, tetrahydrofuranyl), – OR ^a2 , –N(R ^a2 ) ₂ , –C(=O)R ^a2 , –C(=O)OR ^a2 , –NR ^a4 C(=O)R ^a2 , –NR ^a2 C(=O)OR ^a2 , – C(=O)N(R ^a2 ) ₂ , –OC(=O)N(R ^a2 ) ₂ , wherein each R ^a2 is as defined in any of the embodiments described herein. In some embodiments, each R ² is independently selected from the group consisting of halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl), 3-6 membered heterocyclyl (e.g., oxetanyl, tetrahydrofuranyl), –OR ^a2 , –N(R ^a2 ) _2, –C(=O)R ^a2 , –C(=O)N(OR ^a2 )(R ^a2 ), and –C(=O)N(R ^a2 ) ₂ , wherein each R ^a2 is as defined in any of the embodiments described herein. In some embodiments, each R ^a2 is independently selected from the group consisting of H, –CF ₃ , and –C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu). [0417] In some embodiments, each R ² is independently selected from the group consisting of halo (e.g., –Cl), –C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu), – C ₁ –C ₆ haloalkyl (e.g., –CF ₃ , –CHF ₂ ) and ––OCH ₃ . [0418] In some embodiments, each R ² is independently selected from the group consisting of halo (e.g., –Cl), –C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu), – C ₁ –C ₆ haloalkyl (e.g., –CF ₃ , –CHF ₂ ), –C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl), –C ₁ – C ₆ haloalkoxy, (e.g., –OCF ₃ , –OCHF ₂ ), ––OCH ₃ , –C(=O)H, –C(=O)NHOH, and –C(=O)NH ₂ [0419] In some embodiments, each R ² is independently selected from the group consisting of halo (e.g., –Cl), –C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu), – C ₁ –C ₆ haloalkyl (e.g., –CF ₃ , –CHF ₂ ), –C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl), and ––OCH _3. [0420] In some embodiments, each R ² is independently selected from the group consisting of halo (e.g., –Cl), –C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu) and ––OCH ₃ . [0421] In some embodiments, each R ² is independently selected from the group consisting of –F, –Me, –CF ₃ and ––OCH ₃ . [0422] In some embodiments, each R ² is independently selected from the group consisting of –Me, –Et, – ^t Bu, –CF ₃ , cyclobutyl and ––OCH ₃ . [0423] In some embodiments, R ² is –D. [0424] In certain embodiments, R ² is =O. [0425] In certain embodiments, R ² is halo (e.g., fluoro, chloro, bromo, iodo). In some embodiments, R ² is –Cl. In some embodiments, R ² is –F. In some embodiments, R ² is –Br. In some embodiments, R ² is –I. [0426] In some embodiments, R ² is –CN. [0427] In certain embodiments, R ² is –C ₁ –C ₆ alkyl. In some embodiments, R ² is –Me. In some embodiments, R ² is –Et. In some embodiments R ² is –Pr or –iPr. [0428] In some embodiments, R ² is –C ₁ –C ₆ heteroalkyl. In some embodiments, R ² is methoxymethyl (–CH ₂ OCH ₃ ). In some embodiments, R ² is hydroxymethyl (-CH ₂ OH). In some embodiments, R ² is aminomethyl (e.g.,–CH ₂ NH ₂ , –CH ₂ NHCH ₃ , –CH ₂ N(CH ₃ ) ₂ . In some embodiments, R ² is –C ₁ –C ₆ haloalkyl. In some embodiments, R ² is trifluoromethyl (–CF ₃ ). [0429] In some embodiments, R ² is C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl). In some embodiments, R ² is cyclopropyl. In some embodiments R ² is cyclobutyl. In some embodiments, R ² is cyclopentyl. In some embodiments, R ² is cyclohexyl. [0430] In some embodiments, R ² is 3-10 membered heterocyclyl (e.g., oxetanyl, tetrahydropyranyl, tetrahydrofuranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl). In some embodiments, R ² is 3-6 membered heterocyclyl (e.g., oxetanyl, tetrahydropyranyl, tetrahydrofuranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl). In some embodiments, R ² is oxetanyl. In some embodiments, R ² is tetrahydropyranyl. In some embodiments, R ² is tetrahydrofuranyl. In some embodiments, R ² is azetidinyl. In some embodiments, R ² is pyrrolidinyl. In some embodiments, R ² is piperidinyl. In some embodiments, R ² is piperazinyl. In some embodiments, R ² is morpholinyl. In some embodiments, R ² is azepanyl. [0431] In some embodiments R ² is cycloalkylalkyl (e.g., cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl). In some embodiments, R ² is heterocyclylalkyl (e.g., oxetanylmethyl, aziridinylmethyl, tetrahydrofuranylmethyl, pyrrolidinylmethyl, tetrahydropyranylmethyl, piperidinylmethyl, piperazinylmethyl, morpholinylmethyl, azepanylmethyl). In some embodiments, R ² is arylalkyl (e.g., benzyl). In some embodiments, R ² is heteroarylalkyl (e.g., pyridinylmethyl, thiazolylmethyl, triazolylmethyl, pyrazolylmethyl). [0432] In some embodiments, R ² is –CH ₂ C(=O)N(R ^a2 ) ₂ (e.g., –CH ₂ C(=O)N(R ^a2 ) ₂ ). [0433] In some embodiments, R ² is –OR ^a2 wherein R ^a2 is as defined in any of the embodiments described herein (e.g., –OH, methoxy, isopropoxy, difluoromethoxy (–OCHF ₂ ), trifluoromethoxy (–OCF ₃ ), ethoxy, propoxy, isopropoxy, cyclopropyloxy, cyclobutyloxy). In some embodiments R ² is –OH. In some embodiments, R ² is methoxy. In some embodiments, R ² is ethoxy. In some embodiments, R ² is propoxy. In some embodiments, R ² is isopropoxy. In some embodiments, R ² is –C ₁ –C ₆ haloalkoxy, (e.g., –OCF ₃ , –OCHF ₂ ). In some embodiments R ² is difluoromethoxy. (–OCHF ₂ ). In some embodiments, R ² is trifluoromethoxy (–OCF ₃ ). [0434] In some embodiments, R ² is –N(R ^a2 ) ₂ wherein R ^a2 is as defined in any of the embodiments described herein (e.g., –NH ₂ , –NHR ^a2 , –N(CH ₃ )R ^a2 ). In some embodiments, R ² is –NH ₂ . In some embodiments, R ² is –NHR ^a2 (e.g., –NHCH ₃ , –NHCH ₂ CH ₃ , –NHPr, – NH ⁱ Pr, –NHcyclopropyl, –NHcyclobutyl). In some embodiments, R ² is –N(CH ₃ )R ^a2 (e.g., – N(CH ₃ ) ₂ , –N(CH ₃ )CH ₂ CH ₃ , –N(CH ₃ )CH ₂ CH ₂ CH ₃ , –N(CH ₃ ) ⁱ Pr, –N(CH ₃ )cyclopropyl, – N(CH ₃ )cyclobutyl). [0435] In some embodiments, R ² is –C(=O)R ^a2 wherein R ^a2 is as described herein. In some embodiments R ² is –C(=O)R ^a2 wherein R ^a2 is C ₁ -C ₆ alkyl, C ₃ -C ₉ cycloalkyl or 3-10 membered heterocyclyl (e.g., –C(=O)CH ₃ , –C(=O)CH ₂ CH ₃ , –C(=O) ^t Bu, –C(=O) ⁱ Pr, – C(=O)CH ₂ CH ₂ CH ₃ , –C(=O)cyclopropyl, –C(=O)cyclobutyl, –C(=O)oxetanyl, – C(=O)tetrahydropyranyl). In some embodiments, R ² is –C(=O)CH ₃ , –C(=O)CH ₂ CH ₃ , – C(=O) ^t Bu, –C(=O) ⁱ Pr or –C(=O)CH ₂ CH ₂ CH ₃ . In some embodiments, R ² is –C(=O) ⁱ Pr. [0436] In some embodiments, R ² is –C(=O)OR ^a2 wherein R ^a2 is as described herein. In some embodiments R ² is –C(=O)OR ^a2 wherein R ^a2 is C ₁ -C ₆ alkyl or C ₃ -C ₉ cycloalkyl (e.g., – C(=O)OCH ₃ , –C(=O)OCH ₂ CH ₃ , –C(=O)O ^t Bu, –C(=O)O ⁱ Pr, –C(=O)OCH ₂ CH ₂ CH ₃ , – C(=O)Ocyclopropyl, –C(=O)Ocyclobutyl). In some embodiments, R ² is –C(=O)OCH ₃ , – C(=O)OCH ₂ CH ₃ , –C(=O)O ^t Bu, –C(=O) ⁱ Pr or –C(=O)OCH ₂ CH ₂ CH ₃ . In some embodiments, R ² is –C(=O)O ⁱ Pr. [0437] In some embodiments, R ² is –NR ^a2 C(=O)R ^a2 wherein R ^a2 is as described herein. In certain embodiments, R ² is –NHC(=O)R ^a2 (e.g., –NHC(=O)CH ₃ , –NHC(=O)CH ₂ CH ₃ , – NHC(=O)CH ₂ CH ₂ CH ₃ , –NHC(=O) ⁱ Pr, –NHC(=O)Bu, –NHC(=O) ^t Bu, – NHC(=O)Cyclopropyl, –NHC(=O)Cyclobutyl). In certain embodiments, R ² is NHC(=O)CH ₃ . In some embodiments, R ² is –N(CH ₃ )C(=O)R ^a2 (e.g., –N(CH ₃ )C(=O)CH ₃ , – N(CH ₃ )C(=O)CH ₂ CH ₃ , –N(CH ₃ )C(=O)CH ₂ CH ₂ CH ₃ , –N(CH ₃ )C(=O) ⁱ Pr, –N(CH ₃ )C(=O)Bu, –N(CH ₃ )C(=O) ^t Bu, –N(CH ₃ )C(=O)Cyclopropyl, –N(CH ₃ )C(=O)Cyclobutyl). [0438] In some embodiments, R ² is –NR ^a2 C(=O)OR ^a2 wherein R ^a2 is as described herein. In certain embodiments, R ² is –NHC(=O)OR ^a2 (e.g., –NHC(=O)OCH ₃ , – NHC(=O)OCH ₂ CH ₃ , –NHC(=O)OCH ₂ CH ₂ CH ₃ , –NHC(=O)O ⁱ Pr, –NHC(=O)OBu, – NHC(=O)O ^t Bu, –NHC(=O)OCyclopropyl, –NHC(=O)OCyclobutyl). In some embodiments, R ² is –N(CH ₃ )C(=O)OR ^a2 (e.g., –N(CH ₃ )C(=O)OCH ₃ , –N(CH ₃ )C(=O)OCH ₂ CH ₃ , – N(CH ₃ )C(=O)OCH ₂ CH ₂ CH ₃ , –N(CH ₃ )C(=O)O ⁱ Pr, –N(CH ₃ )C(=O)OBu, – N(CH ₃ )C(=O)O ^t Bu, –N(CH ₃ )C(=O)OCyclopropyl, –N(CH ₃ )C(=O)OCyclobutyl). [0439] In some embodiments, R ² is –C(=O)N(R ^a2 ) ₂ wherein R ^a2 is as described herein (e.g., –C(=O)NH ₂ , –C(=O)NHR ^a2 , –C(=O)N(CH ₃ )R ^a2 ). In some embodiments, R ² is –C(=O)NH ₂ . In certain embodiments, R ² is –C(=O)NHR ^a2 (e.g., –C(=O)NHCH ₃ , –C(=O)NHCH ₂ CH ₃ , – C(=O)NHPr, –C(=O)NH ⁱ Pr, –C(=O)NHBu, –C(=O)NH ^t Bu, –C(=O)NHCyclopropyl, – C(=O)NHCyclobutyl). In certain embodiments, R ² is –C(=O)N(CH ₃ )R ^a2 (e.g., – C(=O)N(CH ₃ ) ₂ , –C(=O)N(CH ₃ )CH ₂ CH ₃ , –C(=O)N(CH ₃ )CH ₂ CH ₂ CH ₃ , –C(=O)N(CH ₃ ) ⁱ Pr, – C(=O)N(CH ₃ )Bu, –C(=O)N(CH ₃ ) ^t Bu, –C(=O)N(CH ₃ )Cyclopropyl, – C(=O)N(CH ₃ )Cyclobutyl). [0440] In some embodiments, R ² is –OC(=O)N(R ^a2 ) ₂ wherein R ^a2 is as described herein. In certain embodiments, R ² is –OC(=O)NHR ^a2 (e.g., –OC(=O)NHCH ₃ , –OC(=O)NHCH ₂ CH ₃ , – OC(=O)NHPr, –OC(=O)NH ⁱ Pr, –OC(=O)NHBu, –OC(=O)NH ^t Bu, – OC(=O)NHCyclopropyl, –OC(=O)NHCyclobutyl). In certain embodiments, R ² is – OC(=O)N(CH ₃ )R ^a2 (e.g., –OC(=O)N(CH ₃ ) ₂ , –OC(=O)N(CH ₃ )CH ₂ CH ₃ , – OC(=O)N(CH ₃ )CH ₂ CH ₂ CH ₃ , –OC(=O)N(CH ₃ ) ⁱ Pr, –OC(=O)N(CH ₃ )Bu, – OC(=O)N(CH ₃ ) ^t Bu, –OC(=O)N(CH ₃ )Cyclopropyl, –OC(=O)N(CH ₃ )Cyclobutyl). [0441] In some embodiments, R ² is –S(=O)R ^a2 wherein R ^a2 is as described herein. In certain embodiments, R ² is –S(=O)alkyl (e.g., –S(=O)CH ₃ , –S(=O)CH ₂ CH ₃ , – S(=O)CH ₂ CH ₂ CH ₃ , –S(=O) ⁱ Pr). In certain embodiments, R ² is –S(=O)cycloalkyl (e.g., – S(=O)cyclopropyl, –S(=O)cyclobutyl, –S(=O)cyclopentyl, –S(=O)cyclohexyl). [0442] In some embodiments, R ² is –S(=O) ₂ R ^a2 . In certain embodiments, R ² is – S(=O) ₂ alkyl (e.g., –S(=O) ₂ CH ₃ , –S(=O) ₂ CH ₂ CH ₃ , –S(=O) ₂ Pr, –S(=O) ₂ ⁱ Pr). In certain embodiments, R ² is –S(=O) ₂ cycloalkyl (e.g., –S(=O) ₂ cyclopropyl, –S(=O) ₂ cyclobutyl, – S(=O) ₂ cyclopentyl, –S(=O) ₂ cyclohexyl). In some embodiments, R ² is S(=O) ₂ aryl (e.g., – S(=O) ₂ phenyl). [0443] In some embodiments, R ² is –SR ^a2 wherein R ^a2 is as described herein. In certain embodiments, R ² is –Salkyl (e.g., –SCH ₃ , –SCH ₂ CH ₃ , –SPr, –S ⁱ Pr). In certain embodiments, R ² is –Scycloalkyl (e.g., –Scyclopropyl, –Scyclobutyl, –Scyclopentyl, –Scyclohexyl). In certain embodiments, R ² is –Saryl (e.g., –Sphenyl). [0444] In some embodiments, R ² is –S(=O)(=NR ^a2 )R ^a2 wherein R ^a2 is as described herein. In certain embodiments, R ² is –S(=O)(=NH)R ^a2 (e.g., –S(=O)(=NH)CH ₃ , – S(=O)(=NH)CH ₂ CH ₃ , –S(=O)(=NH)CH ₂ CH ₂ CH ₃ , –S(=O)(=NH) ⁱ Pr, –S(=O)(=NH)Bu, – S(=O)(=NH) ^t Bu, –S(=O)(=NH)Cyclopropyl, –S(=O)(=NH)Cyclobutyl). In some embodiments, R ² is –S(=O)(=NCH ₃ )R ^a2 (e.g., –S(=O)(=NCH ₃ )CH ₃ , – S(=O)(=NCH ₃ )CH ₂ CH ₃ , –S(=O)(=NCH ₃ )CH ₂ CH ₂ CH ₃ , –S(=O)(=NCH ₃ ) ⁱ Pr, – S(=O)(=NCH ₃ )Bu, –S(=O)(=NCH ₃ ) ^t Bu, –S(=O)(=NCH ₃ )Cyclopropyl, – S(=O)(=NCH ₃ )Cyclobutyl). [0445] In some embodiments, R ² is –NR ^a2 S(=O) ₂ R ^a2 wherein R ^a2 is as described herein. In certain embodiments, R ² is –NHS(=O) ₂ alkyl (e.g., –NHS(=O) ₂ CH ₃ , –NHS(=O) ₂ CH ₂ CH ₃ , – NHS(=O) ₂ Pr, –NHS(=O) ₂ ⁱ Pr). In certain embodiments, R ² is –NHS(=O) ₂ cycloalkyl (e.g., – NHS(=O) ₂ cyclopropyl, –NHS(=O) ₂ cyclobutyl, –NHS(=O) ₂ cyclopentyl, – NHS(=O) ₂ cyclohexyl). In certain embodiments, R ² is –N(CH ₃ )S(=O) ₂ alkyl (e.g., – N(CH ₃ )S(=O) ₂ CH ₃ , –N(CH ₃ )S(=O) ₂ CH ₂ CH ₃ , –N(CH ₃ )S(=O) ₂ Pr, –N(CH ₃ )S(=O) ₂ ⁱ Pr). In certain embodiments, R ² is –N(CH ₃ )S(=O) ₂ cycloalkyl (e.g., –N(CH ₃ )S(=O) ₂ cyclopropyl, – N(CH ₃ )S(=O) ₂ cyclobutyl, –N(CH ₃ )S(=O) ₂ cyclopentyl, –N(CH ₃ )S(=O) ₂ cyclohexyl). [0446] In some embodiments, R ² is –S(=O) ₂ N(R ^a2 ) ₂ wherein R ^a2 is as described herein. (e.g., –S(=O) ₂ NH ₂ , –S(=O) ₂ NHR ^a2 , –S(=O) ₂ N(CH ₃ )R ^a2 ). In some embodiments, R ² is – S(=O) ₂ NH ₂ . In some embodiments, R ² is –S(=O) ₂ NHR ^a2 (e.g., –S(=O) ₂ NHCH ₃ , – S(=O) ₂ NHCH ₂ CH ₃ , –S(=O) ₂ NHPr, –S(=O) ₂ NH ⁱ Pr, –S(=O) ₂ NHcyclopropyl, – S(=O) ₂ NHcyclobutyl). In some embodiments, R ² is –S(=O) ₂ N(CH ₃ )R ^a2 (e.g., – S(=O) ₂ N(CH ₃ ) ₂ , –S(=O) ₂ N(CH ₃ )CH ₂ CH ₃ , –S(=O) ₂ N(CH ₃ )CH ₂ CH ₂ CH ₃ , –S(=O) ₂ N(CH ₃ ) ⁱ Pr, –S(=O) ₂ N(CH ₃ )cyclopropyl, –S(=O) ₂ N(CH ₃ )cyclobutyl). [0447] As generally defined herein, each R ³ is independently selected from the group consisting of –D, =O, –CN, halo, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ – C ₉ cycloalkyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, –OR ^a3 , –N(R ^a3 ) ₂ , –C(=O)R ^a3 , – C(=O)OR ^a3 , –NR ^a3 C(=O)R ^a3 , –NR ^a3 C(=O)OR ^a3 , –C(=O)N(R ^a3 ) ₂ , –OC(=O)R ^a3 , – OC(=O)N(R ^a3 ) ₂ , –S(=O)R ^a3 , –S(=O) ₂ R ^a3 , –SR ^a3 , –S(=O)(=NR ^a3 )R ^a3 , –NR ^a3 S(=O) ₂ R ^a3 and – S(=O) ₂ N(R ^a3 ) ₂ , wherein R ^a3 is as described herein, and wherein each alkyl, cycloalkyl, heteroalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl and heteroarylalkyl of R ³ is optionally substituted at any available position (e.g., substituted with 0, 1, 2, 3, 4, or 5 instances of R ⁶ , wherein each R ⁶ is as described herein. [0448] In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl and heteroarylalkyl of R ³ is unsubstituted. In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl and heteroarylalkyl of R ³ is independently substituted with 1 instance of R ⁶ . In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl and heteroarylalkyl of R ³ is independently substituted with 2 instances of R ⁶ . In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl and heteroarylalkyl of R ³ is independently substituted with 3 instances of R ⁶ . In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl and heteroarylalkyl of R ³ is independently substituted with 4 instances of R ⁶ . In some embodiments, each alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl and heteroarylalkyl of R ³ is independently substituted with 5 instances of R ⁶ . [0449] In some embodiments, each R ³ is independently selected from the group consisting of –D, =O, halo (e.g., –F, –Cl, Br), –CN, –C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr, –sec–Bu, – ^t Bu, –CH ₂ (CH ₃ )( ⁱ Pr)), –C ₁ –C ₆ heteroalkyl (e.g., –CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )CH ₂ N(CH ₃ ) ₂ , – CH ₂ CH ₂ N(CH ₃ ) ₂ , –CH ₂ C(CH ₃ ) ₂ N(CH ₃ ) ₂ , –CH ₂ CH ₂ CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )N(CH ₃ ) ₂ , – CH ₂ CH(CH ₃ )N(CH ₃ ) ₂ , –CH ₂ OH, –CH(OH)(CH ₃ ) _, –C(OH)(CH ₃ ) ₂ , –CH ₂ NH ₂ ), –C ₁ –C ₆ haloalkyl (e.g., –CHF ₂ , –CH ₂ CF ₃ , –CF ₃ ), –C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl), 3-10 membered heterocyclyl (e.g., tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, morpholinyl, pyrrolidinyl, piperidinyl, piperidin-2-onyl, tetrahydropyridinyl (e.g., 1,2,3,6 tetrahydropyridinyl), piperazinyl, piperazin-2-onyl, azetidinyl, decahydro-1,6-naphthyridinyl, 2-azaspiro[3.3]heptanyl, 5-oxa-2,8- diazaspiro[3.5]nonanyl, 8-azabicyclo[3.2.1]octanyl, 2-azabicyclo[2.2.2]octanyl, 1- azabicyclo[2.2.1]heptanyl, 3-azabicyclo[3.2.0]heptanyl, 3-azabicyclo[3.1.1]heptanyl, 3- azabicyclo[3.1.0]hexanyl, 2-azabicyclo[2.1.1]hexanyl, 1-azabicyclo[2.2.1]heptanyl, 3- azabicyclo[3.2.0]heptanyl, bicyclo[1.1.1]pentanyl, octahydrocyclopenta[c]pyrrolyl, decahydro-1,6-naphthyridinyl, octahydro-1H-pyrrolo[3,4-c]pyridinyl, decahydro-2,7- naphthyridinyl), cycloalkylalkyl (e.g., –CH ₂ -cyclopropyl), heterocyclylalkyl (e.g., –CH ₂ - morpholinyl, –CH ₂ -pyrrolidinyl, –CH(CH ₃ )CH ₂ -pyrrolidinyl, –(CH ₂ ) ₂ -pyrrolidinyl, –(CH ₂ ) ₃ - pyrrolidinyl, –CH ₂ -morpholinyl, –(CH ₂ ) ₂ -morpholinyl), –OR ^a3 (e.g., –OH, –OCH ₃ , – OCH ₂ CH ₃ , –OCH ₂ CH ₂ N(CH ₃ ) ₂ , –O-tetrahydrofuranyl, –O-tetrahydropyran-4-yl, –OCF ₃ , – OCHF ₂ , –OCH ₂ CH(CH ₃ )N(CH ₃ ) ₂ , –Opiperidinyl, –O-(CH ₂ ) ₂ -pyrrolidinyl, –O-CH ₂ - piperidinyl, –O-CH ₂ -oxetanyl, –O-CH ₂ -tetrahydrofuranyl, –O-CH ₂ -tetrahydropyranyl), – N(R ^a3 ) ₂ , (e.g., –NH ₂ , –NHR ^a3 , –NHCH ₃ , –N(CH ₃ ) ₂ , –NHCH ₂ CF ₃ , –NH-oxetan-3-yl, –NH- (N-Me-2-oxo-pyrrolidin-3-yl) and –C(=O)N(R ^a3 ) ₂ , (e.g., –C(=O)NH ₂ , –C(=O)NHCH ₃ , – C(=O)CH ₂ CH ₂ N(CH ₃ ) ₂ ), wherein each alkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl and heteroarylalkyl is optionally substituted (e.g., with 0, 1, 2, 3, 4, or 5 instances of R ⁶ , and wherein each R ^a3 is as described herein. [0450] In some embodiments, each R ³ is independently selected from the group consisting of D, –CN, halo (e.g., –F, –Cl, Br), –C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr, –sec–Bu, – ^t Bu, – CH ₂ (CH ₃ )( ⁱ Pr)), –C ₁ –C ₆ heteroalkyl (e.g., –CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )CH ₂ N(CH ₃ ) ₂ , – CH ₂ CH ₂ N(CH ₃ ) ₂ , –CH ₂ C(CH ₃ ) ₂ N(CH ₃ ) ₂ , –CH ₂ CH ₂ CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )N(CH ₃ ) ₂ , – CH ₂ CH(CH ₃ )N(CH ₃ ) ₂ ,) –C ₁ –C ₆ haloalkyl, (e.g., –CF ₃ ), –C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl), 3-10 membered heterocyclyl (e.g., tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, morpholinyl, pyrrolidinyl, piperidinyl, tetrahydropyridinyl (e.g., 1,2,3,6 tetrahydropyridinyl), piperidin-2-onyl, piperazinyl, piperazin-2-onyl, azetidinyl, decahydro-1,6-naphthyridinyl, 2-azaspiro[3.3]heptanyl, 5-oxa-2,8-diazaspiro[3.5]nonanyl, 8- azabicyclo[3.2.1]octanyl, 2-azabicyclo[2.2.2]octanyl, 1-azabicyclo[2.2.1]heptanyl, 3- azabicyclo[3.2.0]heptanyl, 3-azabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.1.0]hexanyl, 2- azabicyclo[2.1.1]hexanyl, 1-azabicyclo[2.2.1]heptanyl, 3-azabicyclo[3.2.0]heptanyl, bicyclo[1.1.1]pentanyl, octahydrocyclopenta[c]pyrrolyl, decahydro-1,6-naphthyridinyl, octahydro-1H-pyrrolo[3,4-c]pyridinyl, decahydro-2,7-naphthyridinyl), cycloalkylalkyl (e.g., –CH ₂ -cyclopropyl), heterocyclylalkyl (e.g., –CH ₂ -morpholinyl, –CH ₂ -piperidinyl, –CH ₂ - pyrrolidinyl, –CH(CH ₃ )CH ₂ -pyrrolidinyl, –(CH ₂ ) ₂ -pyrrolidinyl, –(CH ₂ ) ₃ -pyrrolidinyl), –OR ^a3 (e.g., –OH, –OCH ₃ , –OCH ₂ CH ₃ , –OCH ₂ CH ₂ N(CH ₃ ) ₂ , –OCH ₂ CH(CH ₃ )N(CH ₃ ) ₂ , –OCF ₃ , – OCHF ₂ , –O-piperidinyl, –OCH ₂ -pyrrolidinyl), –NR ^a3 ) ₂ , –NR ^a3 C(=O)R ^a3 (e.g., – NHC(=O)CH ₃ ), –NHC(=O)CH ₂ CH ₂ N(CH ₃ ) ₂ ), wherein each alkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, and heterocyclylalkyl is optionally substituted (e.g., with 0, 1, 2, 3, 4, or 5 instances of R ⁶ ; and each R ^a3 is independently selected from the group consisting of H, –C ₁ –C ₆ alkyl, (e.g., –Me, – Et, –Pr, – ⁱ Pr, –sec-Bu, – ^t Bu), –C ₁ –C ₆ haloalkyl (e.g., –CF ₃ , –CHF ₂ , –CH ₂ CF ₃ ), –C ₁ –C ₆ heteroalkyl substituted with 0 or 1 instances of =O (e.g., –CH ₂ CH ₂ N(CH ₃ ) ₂ , – CH ₂ CH(CH ₃ )N(CH ₃ ) ₂ , –CH ₂ C(=O)N(CH ₃ ) ₂ , –CH(CH ₃ )CH ₂ N(CH ₃ ) ₂ , – CH(CH ₃ )C(=O)N(CH ₃ ) ₂ )), C ₃ -C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl), heterocyclylalkyl (e.g., –CH ₂ (N-methyl pyrrolidin-2-yl)) and 3-10 membered heterocyclyl (e.g., piperidinyl, e.g., N-methyl piperidin-4-yl), wherein each R ⁶ is as define in any of the embodiments described herein. [0451] In some embodiments, each R ³ is independently selected from the group consisting of –CN, halo (e.g., –F, –Cl, Br), –C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr, –sec–Bu, – ^t Bu, – CH ₂ (CH ₃ )( ⁱ Pr)), –C ₁ –C ₆ heteroalkyl (e.g., –CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )CH ₂ N(CH ₃ ) ₂ , – CH ₂ CH ₂ N(CH ₃ ) ₂ , –CH ₂ C(CH ₃ ) ₂ N(CH ₃ ) ₂ , –CH ₂ CH ₂ CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )N(CH ₃ ) ₂ , – CH ₂ CH(CH ₃ )N(CH ₃ ) ₂ ,) –C ₁ –C ₆ haloalkyl, (e.g., –CF ₃ ), –C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl), 3-10 membered heterocyclyl (e.g., tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, morpholinyl, pyrrolidinyl, piperidinyl, tetrahydropyridinyl (e.g., 1,2,3,6 tetrahydropyridinyl), piperidin-2-onyl, piperazinyl, piperazin-2-onyl, azetidinyl, decahydro-1,6-naphthyridinyl, 2-azaspiro[3.3]heptanyl, 5-oxa-2,8-diazaspiro[3.5]nonanyl, 8- azabicyclo[3.2.1]octanyl, 2-azabicyclo[2.2.2]octanyl, 1-azabicyclo[2.2.1]heptanyl, 3- azabicyclo[3.2.0]heptanyl, 3-azabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.1.0]hexanyl, 2- azabicyclo[2.1.1]hexanyl, 1-azabicyclo[2.2.1]heptanyl, 3-azabicyclo[3.2.0]heptanyl, bicyclo[1.1.1]pentanyl, octahydrocyclopenta[c]pyrrolyl, decahydro-1,6-naphthyridinyl, octahydro-1H-pyrrolo[3,4-c]pyridinyl, decahydro-2,7-naphthyridinyl), cycloalkylalkyl (e.g., –CH ₂ -cyclopropyl), heterocyclylalkyl (e.g., –CH ₂ -morpholinyl, –CH ₂ -piperidinyl, –CH ₂ - pyrrolidinyl, –CH(CH ₃ )CH ₂ -pyrrolidinyl, –(CH ₂ ) ₂ -pyrrolidinyl, –(CH ₂ ) ₃ -pyrrolidinyl), –OR ^a3 (e.g., –OH, –OCH ₃ , –OCH ₂ CH ₃ , –OCH ₂ CH ₂ N(CH ₃ ) ₂ , –OCH ₂ CH(CH ₃ )N(CH ₃ ) ₂ , –OCF ₃ , – OCHF ₂ , –O-piperidinyl, –OCH ₂ -pyrrolidinyl), –NR ^a3 C(=O)R ^a3 (e.g., –NHC(=O)CH ₃ ), – NHC(=O)CH ₂ CH ₂ N(CH ₃ ) ₂ ), wherein each alkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, and heterocyclylalkyl is optionally substituted (e.g., with 0, 1, 2, 3, 4, or 5 instances of R ⁶ , wherein R ⁶ is as described herein). [0452] In some embodiments, R ³ is independently selected from the group consisting of – Me, –CN, –F, –Cl, –Br, –CF ₃ , –Et, –Pr, – ⁱ Pr, –sec–Bu, – ^t Bu, –CH ₂ (CH ₃ )( ⁱ Pr), –CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )CH ₂ N(CH ₃ ) ₂ , –CH ₂ CH ₂ N(CH ₃ ) ₂ , –CH ₂ CH ₂ CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )N(CH ₃ ) ₂ , – CH ₂ CH(CH ₃ )N(CH ₃ ) ₂ , –CH(CH ₃ )N(CH ₃ ) ₂ , –CH ₂ C(CH ₃ ) ₂ N(CH ₃ ) ₂ , cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, morpholinyl, pyrrolidinyl, piperidinyl, tetrahydropyridinyl (e.g., 1,2,3,6 tetrahydropyridinyl) piperidin-2- onyl, piperazinyl, piperazin-2-onyl, azetidinyl, decahydro-1,6-naphthyridinyl, 2- azaspiro[3.3]heptanyl, 5-oxa-2,8-diazaspiro[3.5]nonanyl, 8-azabicyclo[3.2.1]octanyl, 2- azabicyclo[2.2.2]octanyl, 1-azabicyclo[2.2.1]heptanyl, 3-azabicyclo[3.2.0]heptanyl, 3- azabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.1.0]hexanyl, 2-azabicyclo[2.1.1]hexanyl, 1- azabicyclo[2.2.1]heptanyl, 3-azabicyclo[3.2.0]heptanyl, bicyclo[1.1.1]pentanyl, octahydrocyclopenta[c]pyrrolyl, decahydro-1,6-naphthyridinyl, octahydro-1H-pyrrolo[3,4- c]pyridinyl, decahydro-2,7-naphthyridinyl, –CH ₂ -cyclopropyl, –CH ₂ -morpholinyl, –CH ₂ - piperidinyl, –CH ₂ -pyrrolidinyl, –CH(CH ₃ )CH ₂ -pyrrolidinyl, –(CH ₂ ) ₂ -pyrrolidinyl, –(CH ₂ ) ₃ - pyrrolidinyl), –OH, –OCH ₃ , –OCH ₂ CH ₃ , –OCH ₂ CH ₂ N(CH ₃ ) ₂ , –OCF ₃ , – OCH ₂ CH(CH ₃ )N(CH ₃ ) ₂ , –OCH ₂ (pyrrolidinyl), –Opiperidinyl, –OCHF ₂ , –C(=O)CH ₃ ), and – C(=O)CH ₂ CH ₂ N(CH ₃ ) ₂ ), each optionally substituted (e.g., with 0, 1, 2, 3, 4, or 5 instances of R ⁶ , wherein R ⁶ is as described herein). [0453] In some embodiments, each R ³ is independently selected from the group consisting of D, –CN, –Me, –Et, – ⁱ Pr, –F, –Cl, –CF ₃ , –N(CH ₃ ) ₂ , –N(CH ₂ CH ₃ ) ₂ , –N(CH ₃ )CH ₂ CH ₃ , – OMe, –OEt, –O-cyclopropyl, –CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )CH ₂ N(CH ₃ ) ₂ , –CH ₂ CH ₂ N(CH ₃ ) ₂ , – CH ₂ CH ₂ CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )N(CH ₃ ) ₂ , –CH ₂ C(CH ₃ ) ₂ N(CH ₃ ) ₂ , cyclopropyl, cyclobutyl, cyclohexyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, morpholinyl, pyrrolidinyl, piperidinyl, tetrahydropyridinyl (e.g., 1,2,3,6 tetrahydropyridinyl), piperidin-2-onyl, piperazinyl, azetidinyl, 2-azaspiro[3.3]heptanyl, 2-azabicyclo[2.2.2]octanyl, 2- azabicyclo[2.2.1]heptanyl, 1-azabicyclo[2.2.1]heptanyl, –CH ₂ -piperidinyl, –CH ₂ - pyrrolidinyl, –CH(CH ₃ )CH ₂ -pyrrolidinyl, –(CH ₂ ) ₂ -pyrrolidinyl, –(CH ₂ ) ₃ -pyrrolidinyl, – OCH ₂ CH ₂ N(CH ₃ ) ₂ ,–OCH ₂ CH(CH ₃ )N(CH ₃ ) ₂ , –OCH ₂ (pyrrolidinyl), –Opiperidinyl, and – NHC(=O)CH ₂ CH ₂ N(CH ₃ ) ₂ ), wherein each cyclopropyl, cyclobutyl, cyclohexyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, morpholinyl, pyrrolidinyl, piperidinyl, tetrahydropyridinyl, piperidin-2-onyl, piperazinyl, azetidinyl, 2-azaspiro[3.3]heptanyl, 2- azabicyclo[2.2.2]octanyl, 1-azabicyclo[2.2.1]heptanyl, 2-azabicyclo[2.2.1]heptanyl, –CH ₂ - piperidinyl, –CH ₂ -pyrrolidinyl, –CH(CH ₃ )CH ₂ -pyrrolidinyl, –(CH ₂ ) ₂ -pyrrolidinyl, –(CH ₂ ) ₃ - pyrrolidinyl, –CH(CH ₃ )CH ₂ -pyrrolidinyl and –(CH ₂ ) ₃ -pyrrolidinyl is optionally substituted (e.g., with 0, 1, 2, 3, 4, or 5 instances of R ⁶ , wherein each R ⁶ is as defined in any of the embodiments described herein). [0454] In some embodiments, each R ³ is independently selected from the group consisting of –CN, –Me, –Et, – ⁱ Pr, –F, –Cl, –CF ₃ , –N(CH ₃ ) ₂ , –N(CH ₃ )CH ₂ CH ₃ , –OMe, –OEt, –OCH ₂ - cyclopropyl, –CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )CH ₂ N(CH ₃ ) ₂ , –CH ₂ CH ₂ N(CH ₃ ) ₂ , – CH ₂ CH ₂ CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )N(CH ₃ ) ₂ , –CH ₂ C(CH ₃ ) ₂ N(CH ₃ ) ₂ , cyclopropyl, cyclobutyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, morpholinyl, pyrrolidinyl, piperidinyl, tetrahydropyridinyl (e.g., 1,2,3,6 tetrahydropyridinyl), piperidin-2-onyl, piperazinyl, azetidinyl, 2-azaspiro[3.3]heptanyl, 2-azabicyclo[2.2.2]octanyl, 1-azabicyclo[2.2.1]heptanyl, –CH ₂ -piperidinyl, –CH ₂ -pyrrolidinyl, –CH(CH ₃ )CH ₂ -pyrrolidinyl, –(CH ₂ ) ₂ -pyrrolidinyl, – (CH ₂ ) ₃ -pyrrolidinyl, –OCH ₂ CH ₂ N(CH ₃ ) ₂ ,–OCH ₂ CH(CH ₃ )N(CH ₃ ) ₂ , –OCH ₂ (pyrrolidinyl), – Opiperidinyl, and –NHC(=O)CH ₂ CH ₂ N(CH ₃ ) ₂ ), wherein each cyclopropyl, cyclobutyl, tetrahydropyranyl, oxetanyl, morpholinyl, pyrrolidinyl, piperidinyl, piperidin-2-onyl, piperazinyl, azetidinyl, 2-azaspiro[3.3]heptanyl, 2-azabicyclo[2.2.2]octanyl, 1- azabicyclo[2.2.1]heptanyl, –CH ₂ -piperidinyl, –CH ₂ -pyrrolidinyl, –(CH ₂ ) ₂ -pyrrolidinyl, – CH(CH ₃ )CH ₂ -pyrrolidinyl and –(CH ₂ ) ₃ -pyrrolidinyl is optionally substituted (e.g., with 0, 1, 2, 3, 4, or 5 instances of R ⁶ ) [0455] In some embodiments, each R ³ is independently selected from the group consisting of –CN, –Me, –F, –Cl, –CF ₃ , –CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )CH ₂ N(CH ₃ ) ₂ , –CH ₂ CH ₂ N(CH ₃ ) ₂ , – CH ₂ CH ₂ CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )N(CH ₃ ) ₂ , –CH ₂ C(CH ₃ ) ₂ N(CH ₃ ) ₂ , cyclopropyl, cyclobutyl, tetrahydrofuranyl, tetrahydropyranyl, oxetanyl, morpholinyl, pyrrolidinyl, piperidinyl, tetrahydropyridinyl (e.g., 1,2,3,6 tetrahydropyridinyl), piperidin-2-onyl, piperazinyl, azetidinyl, 2-azaspiro[3.3]heptanyl, 2-azabicyclo[2.2.2]octanyl, 1-azabicyclo[2.2.1]heptanyl, –CH ₂ -piperidinyl, –CH ₂ -pyrrolidinyl, –CH(CH ₃ )CH ₂ -pyrrolidinyl, –(CH ₂ ) ₂ -pyrrolidinyl, – (CH ₂ ) ₃ -pyrrolidinyl, –OCH ₂ CH ₂ N(CH ₃ ) ₂ ,–OCH ₂ CH(CH ₃ )N(CH ₃ ) ₂ , –OCH ₂ (pyrrolidinyl), – Opiperidinyl, and –NHC(=O)CH ₂ CH ₂ N(CH ₃ ) ₂ ), wherein each cyclopropyl, cyclobutyl, tetrahydropyranyl, oxetanyl, morpholinyl, pyrrolidinyl, piperidinyl, piperidin-2-onyl, piperazinyl, azetidinyl, 2-azaspiro[3.3]heptanyl, 2-azabicyclo[2.2.2]octanyl, 1- azabicyclo[2.2.1]heptanyl, –CH ₂ -piperidinyl, –CH ₂ -pyrrolidinyl, –(CH ₂ ) ₂ -pyrrolidinyl, – CH(CH ₃ )CH ₂ -pyrrolidinyl and –(CH ₂ ) ₃ -pyrrolidinyl is optionally substituted (e.g., with 0, 1, 2, 3, 4, or 5 instances of R ⁶ ). [0456] In some embodiments, each R ³ is independently selected from the group consisting of: D, –CN, –Me, –Et, – ⁱ Pr, –F, –Cl, –CF ₃ , –N(CH ₃ ) ₂ , –N(CH ₃ )CH ₂ CH ₃ , –OMe, –OEt, – OCH ₂ -cyclopropyl, –CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )CH ₂ N(CH ₃ ) ₂ , –CH ₂ CH ₂ N(CH ₃ ) ₂ , – CH ₂ CH ₂ CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )N(CH ₃ ) ₂ , –CH ₂ C(CH ₃ ) ₂ N(CH ₃ ) ₂ , cyclopropyl, cyclobutyl, cyclohexyl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl, oxetan-3-yl, morpholin-2-yl, piperazin-4-yl, pyrrolidin-1-yl, pyrrolidin-3-yl, piperidin-4-yl, piperidin-3-yl, piperidin-2- one-4-yl, 1,2,3,6 tetrahydropyridin-4-yl, azetidin-3-yl, 2-azabicyclo[2.2.2]octan-4-yl, 2- azaspiro[3.3]heptan-6-yl, 1-azabicyclo[2.2.1]heptan-4-yl, 4-azabicyclo[2.2.1]heptan-4-yl, 1- azabicyclo[2.2.1]heptan-3-yl, –CH ₂ -piperidin-4-yl, –CH ₂ -pyrrolidin-1-yl, –(CH ₂ ) ₂ -pyrrolidin- 1-yl, –CH(CH ₃ )CH ₂ -pyrrolidin-1-yl, –O(CH ₂ ) ₂ N(CH ₃ ) ₂ –OCH ₂ (pyrrolidin-2-yl), – Opiperidin-4-yl, –OCH ₂ CH(CH ₃ )N(CH ₃ ) ₂ and –NHC(=O)(CH ₂ ) ₂ N(CH ₃ ) ₂ , wherein each cyclopropyl, cyclobutyl, cyclohexyl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl, oxetan-3- yl, morpholin-2-yl, piperazin-4-yl, pyrrolidin-1-yl, pyrrolidin-3-yl, piperidin-4-yl, piperidin- 3-yl, piperidin-2-one-4-yl, 1,2,3,6 tetrahydropyridin-4-yl, azetidin-3-yl, 2- azabicyclo[2.2.2]octan-4-yl, 2-azaspiro[3.3]heptan-6-yl, 1-azabicyclo[2.2.1]heptan-4-yl, 4- azabicyclo[2.2.1]heptan-4-yl, 1-azabicyclo[2.2.1]heptan-3-yl, –CH ₂ -piperidin-4-yl, –CH ₂ - pyrrolidin-1-yl, –(CH ₂ ) ₂ -pyrrolidin-1-yl and –CH(CH ₃ )CH ₂ -pyrrolidin-1-yl is optionally substituted (e.g., with 0, 1, 2, 3, 4, or 5 instances of R ^6, wherein each R ⁶ is as described in any of the embodiments described herein. [0457] In some embodiments, each R ³ is independently selected from the group consisting of: –CN, –Me, –Et, – ⁱ Pr, –F, –Cl, –CF ₃ , –N(CH ₃ ) ₂ , –N(CH ₃ )CH ₂ CH ₃ , –OMe, –OEt, –OCH ₂ - cyclopropyl, –CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )CH ₂ N(CH ₃ ) ₂ , –CH ₂ CH ₂ N(CH ₃ ) ₂ , – CH ₂ CH ₂ CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )N(CH ₃ ) ₂ , –CH ₂ C(CH ₃ ) ₂ N(CH ₃ ) ₂ , cyclopropyl, cyclobutyl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl, oxetan-3-yl, morpholin-2-yl, piperazin-4-yl, pyrrolidin-3-yl, piperidin-4-yl, piperidin-3-yl, piperidin-2-one-4-yl, 1,2,3,6 tetrahydropyridin- 4-yl, azetidin-3-yl, 2-azabicyclo[2.2.2]octan-4-yl, 2-azaspiro[3.3]heptan-6-yl, 1- azabicyclo[2.2.1]heptan-4-yl, 1-azabicyclo[2.2.1]heptan-3-yl, –CH ₂ -piperidin-4-yl, –CH ₂ - pyrrolidin-1-yl, –(CH ₂ ) ₂ -pyrrolidin-1-yl, –CH(CH ₃ )CH ₂ -pyrrolidin-1-yl, –O(CH ₂ ) ₂ N(CH ₃ ) ₂ – OCH ₂ (pyrrolidin-2-yl), –Opiperidin-4-yl, –OCH ₂ CH(CH ₃ )N(CH ₃ ) ₂ and – NHC(=O)(CH ₂ ) ₂ N(CH ₃ ) ₂ , wherein each cyclopropyl, cyclobutyl, tetrahydropyran-4-yl, oxetan-3-yl, morpholin-2-yl, piperazin-4-yl, pyrrolidin-3-yl, piperidin-4-yl, piperidin-3-yl, piperidin-2-one-4-yl, piperazin-4-yl, azetidin-3-yl, 2-azabicyclo[2.2.2]octan-4-yl, 2- azaspiro[3.3]heptan-6-yl, 1-azabicyclo[2.2.1]heptan-4-yl, –CH ₂ -piperidin-4-yl, –CH ₂ - pyrrolidin-1-yl, –(CH ₂ ) ₂ -pyrrolidin-1-yl and –CH(CH ₃ )CH ₂ -pyrrolidin-1-yl is optionally substituted (e.g., with 0, 1, 2, 3, 4, or 5 instances of R ⁶ ). [0458] In some embodiments, each R ³ is independently selected from the group consisting of: –CN, –Me, –F, –Cl, –CF ₃ , –CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )CH ₂ N(CH ₃ ) ₂ , –CH ₂ CH ₂ N(CH ₃ ) ₂ , – CH ₂ CH ₂ CH ₂ N(CH ₃ ) ₂ , –CH(CH ₃ )N(CH ₃ ) ₂ , –CH ₂ C(CH ₃ ) ₂ N(CH ₃ ) ₂ , cyclopropyl, cyclobutyl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl, oxetan-3-yl, morpholin-2-yl, piperazin-4-yl, pyrrolidin-3-yl, piperidin-4-yl, piperidin-3-yl, piperidin-2-one-4-yl, 1,2,3,6 tetrahydropyridin- 4-yl, azetidin-3-yl, 2-azabicyclo[2.2.2]octan-4-yl, 2-azaspiro[3.3]heptan-6-yl, 1- azabicyclo[2.2.1]heptan-4-yl, 1-azabicyclo[2.2.1]heptan-3-yl, –CH ₂ -piperidin-4-yl, –CH ₂ - pyrrolidin-1-yl, –(CH ₂ ) ₂ -pyrrolidin-1-yl, –CH(CH ₃ )CH ₂ -pyrrolidin-1-yl, –O(CH ₂ ) ₂ N(CH ₃ ) ₂ – OCH ₂ (pyrrolidin-2-yl), –Opiperidin-4-yl, –OCH ₂ CH(CH ₃ )N(CH ₃ ) ₂ and – NHC(=O)(CH ₂ ) ₂ N(CH ₃ ) ₂ , wherein each cyclopropyl, cyclobutyl, tetrahydropyran-4-yl, oxetan-3-yl, morpholin-2-yl, piperazin-4-yl, pyrrolidin-3-yl, piperidin-4-yl, piperidin-3-yl, piperidin-2-one-4-yl, piperazin-4-yl, azetidin-3-yl, 2-azabicyclo[2.2.2]octan-4-yl, 2- azaspiro[3.3]heptan-6-yl, 1-azabicyclo[2.2.1]heptan-4-yl, –CH ₂ -piperidin-4-yl, –CH ₂ - pyrrolidin-1-yl, –(CH ₂ ) ₂ -pyrrolidin-1-yl and –CH(CH ₃ )CH ₂ -pyrrolidin-1-yl is optionally substituted (e.g., with 0, 1, 2, 3, 4, or 5 instances of R ⁶ ). [0459] In some embodiments, R ³ is selected from the group consisting of –D, –CN, –Me, – Et, – ⁱ Pr, –OMe, –OEt, –F, –Cl, –CF ₃ ,

[0460] In some embodiments, R ³ is selected from the group consisting of –D, –CN, –Me, – Et, – ⁱ Pr, –OMe, –OEt, –F, –Cl, –CF ₃ ,

[0461] In some embodiments, R ³ is selected from the group consisting of –D, –CN, –Me, – F, –Cl, –CF ₃ , [0462] In some embodiments R ³ is –D. [0463] In certain embodiments, R ³ is –C ₁ –C ₆ alkyl. In some embodiments, R ³ is –Me. In some embodiments, R ³ is –Et. In some embodiments R ³ is –Pr or – ⁱ Pr. In some embodiments R ³ is – ^t Bu or –sec-Bu. In some embodiments R ³ is –CH ₂ (CH ₃ )( ⁱ Pr). [0464] In certain embodiments, R ³ is halo (e.g., fluoro, chloro, bromo, iodo). In some embodiments, R ³ is –Cl. In some embodiments, R ³ is –F. In some embodiments, R ³ is –Br. In some embodiments, R ³ is –I. [0465] In some embodiments, R ³ is –CN. [0466] In some embodiments, R ³ is –C ₁ –C ₆ heteroalkyl. In some embodiments, R ³ is methoxymethyl (–CH ₂ OCH ₃ ). In some embodiments, R ³ is hydroxymethyl (–CH ₂ OH). In some embodiments, R ³ is –CH(OH)CH ₃ , –C(OH)(CH3) ₂ . In some embodiments, R ³ is aminomethyl (e.g.,–CH ₂ NH ₂ , –CH ₂ NHCH ₃ ,–CH ₂ NHCH ₂ CH ₃ –CH ₂ N(CH ₃ ) ₂ , – CH(CH ₃ )(N(CH ₃ ) ₂ ), –CH(CH ₃ )CH ₂ (N(CH ₃ ) ₂ ), –CH ₂ CH ₂ N(CH ₃ ) ₂ , –CH ₂ CH ₂ CH ₂ N(CH ₃ ) ₂ , – CH ₂ CH ₂ N(Me)(oxetan-3-yl), –CH(CH ₃ )N(CH ₃ ) ₂ , –CH ₂ C(CH ₃ ) ₂ N(CH ₃ ) ₂ , – CH ₂ CH(CH ₃ )(N(CH ₃ ) ₂ ). In some embodiments, the heteroalkyl is further substituted with =O (e.g., –CH ₂ NHC(=O)CH ₃ ). In some embodiments, R ³ is –C ₁ –C ₆ haloalkyl. In some embodiments, R ³ is trifluoromethyl (–CF ₃ ). In other embodiments, R ³ is difluoromethyl (– CHF ₂ ). In some embodiments R ³ is trifluoroethyl (–CH ₂ CF ₃ ) [0467] In some embodiments, R ³ is C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl). In some embodiments, R ³ is cyclopropyl. In some embodiments, the cyclopropyl is substituted with 1 instance of R ⁶ . In some embodiments, R ³ is cycloprop- 1-yl substituted at the 1 position with R ⁶ . In some embodiments R ³ is cyclobutyl. In some embodiments, R ³ is cyclopentyl. In some embodiments, R ³ is cyclohexyl. In some embodiments, the cycloalkyl is substituted with –OH (e.g., hydroxycyclobutyl). In some embodiments, R ³ is In so ³ me embodiments, R is In some embodiments, R ³ is [0468] In some embodiments, R ³ is 3-10 membered heterocyclyl (e.g., oxetanyl, tetrahydropyranyl, tetrahydrofuranyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyridinyl (e.g., 1,2,3,6 tetrahydropyridinyl), piperazinyl, morpholinyl, azepanyl, piperidin-2-onyl, piperazin-2-onyl, decahydro-1,6-naphthyridinyl, 2-azaspiro[3.3]heptanyl, 5-oxa-2,8- diazaspiro[3.5]nonanyl, 8-azabicyclo[3.2.1]octanyl, 2-azabicyclo[2.2.2]octanyl, 3- azabicyclo[3.2.0]heptanyl, 3-azabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.1.0]hexanyl, 2- azabicyclo[2.1.1]hexanyl, 1-azabicyclo[2.2.1]heptanyl, 3-azabicyclo[3.2.0]heptanyl, bicyclo[1.1.1]pentanyl, octahydrocyclopenta[c]pyrrolyl, decahydro-1,6-naphthyridinyl, octahydro-1H-pyrrolo[3,4-c]pyridinyl, decahydro-2,7-naphthyridinyl), each substituted with 0, 1, 2, 3, 4 or 5 instances of R ⁶ . [0469] In some embodiments, R ³ is 3-8 membered monocyclic heterocyclyl (e.g., oxetanyl, tetrahydropyranyl, tetrahydrofuranyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyridinyl (e.g., 1,2,3,6 tetrahydropyridinyl), piperazinyl, morpholinyl, azepanyl, piperidin-2-onyl, piperazin-2-onyl) or 5-10 membered bicyclic heterocyclyl (decahydro-1,6-naphthyridinyl, 2- azaspiro[3.3]heptanyl, 5-oxa-2,8-diazaspiro[3.5]nonanyl, 8-azabicyclo[3.2.1]octanyl, 2- azabicyclo[2.2.2]octanyl, 3-azabicyclo[3.2.0]heptanyl, 3-azabicyclo[3.1.1]heptanyl, 3- azabicyclo[3.1.0]hexanyl, 2-azabicyclo[2.1.1]hexanyl, 1-azabicyclo[2.2.1]heptanyl, 3- azabicyclo[3.2.0]heptanyl, bicyclo[1.1.1]pentanyl, octahydrocyclopenta[c]pyrrolyl, decahydro-1,6-naphthyridinyl, octahydro-1H-pyrrolo[3,4-c]pyridinyl, decahydro-2,7- naphthyridinyl) each substituted with 0, 1, 2, 3, 4 or 5 instances of R ⁶ . [0470] In some embodiments, R ³ is 3-8 membered monocyclic heterocyclyl (e.g., oxetanyl, tetrahydropyranyl, tetrahydrofuranyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyridinyl (e.g., 1,2,3,6 tetrahydropyridinyl), piperazinyl, morpholinyl, azepanyl, piperidin-2-onyl, piperazin-2-onyl), each substituted with 0, 1, 2, 3, 4 or 5 instances of R ⁶ . In some embodiments, R ³ is selected from the group consisting of oxetanyl, tetrahydropyranyl, tetrahydrofuranyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydropyridinyl (e.g., 1,2,3,6 tetrahydropyridinyl), piperazinyl, morpholinyl, azepanyl, piperidin-2-onyl and piperazin-2- onyl, each substituted with 0, 1, 2, 3, 4 or 5 instances of R ⁶ . In some embodiments, R ³ is oxetanyl. In some embodiments, R ³ is tetrahydropyranyl. In some embodiments, R ³ is tetrahydrofuranyl. In some embodiments, R ³ is azetidinyl. In some embodiments, R ³ is pyrrolidinyl. In some embodiments, R ³ is piperidinyl. In some embodiments, R ³ is tetrahydropyridinyl (e.g., 1,2,3,6 tetrahydropyridinyl). In some embodiments, R ³ is piperazinyl. In some embodiments, R ³ is morpholinyl. In some embodiments, R ³ is azepanyl. In some embodiments, R ³ is piperidin-2-onyl. In some embodiments, R ³ is piperazin-2-onyl. [0471] In some embodiments, R ³ is selected from the group consisting of azetidin-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl, oxetan-3-yl, morpholin-2-yl, pyrrolidin-1-yl, pyrrolidin-3-yl, piperidin-4-yl, 1,2,3,6 tetrahydropyridin-4-yl, piperidin-3-yl, piperidin-2-one- 4-yl, piperazin-4-yl and piperazin-2-on-5-yl. In some embodiments, R ³ is selected from the group consisting of azetidin-3-yl, tetrahydropyran-4-yl, oxetan-3-yl, morpholin-2-yl, pyrrolidin-3-yl, piperidin-4-yl, piperidin-3-yl, 1,2,3,6 tetrahydropyridin-4-yl, piperidin-2-one- 4-yl and piperazin-4-yl. [0472] In some embodiments, R ³ is tetrahydrofuran-3-yl. In some embodiments, R ³ is tetrahydropyran-4-yl. In some embodiments, R ³ is oxetan-3-yl. In some embodiments, R ³ is morpholin-2-yl. In some embodiments, R ³ is pyrrolidin-1-yl. In some embodiments, R ³ is pyrrolidin-3-yl. In some embodiments, R ³ is piperidin-4-yl. In some embodiments, R ³ is piperidin-3-yl. In some embodiments, R ³ is 1,2,3,6 tetrahydropyridin-4-yl. In some embodiments, R ³ is piperidin-2-one-4-yl. In some embodiments, R ³ is piperazin-4-yl. In some embodiments, R ³ is piperazin-2-on-5-yl. In some embodiments, R ³ is azetidin-3-yl. [0473] In some embodiments, R ³ is

[0474] In some embodiments, R ³ is a 5-10 membered bicyclic heterocyclyl (e.g., decahydro-1,6-naphthyridinyl, 2-azaspiro[3.3]heptanyl, 5-oxa-2,8-diazaspiro[3.5]nonanyl, 8- azabicyclo[3.2.1]octanyl, 2-azabicyclo[2.2.2]octanyl, 3-azabicyclo[3.2.0]heptanyl, 3- azabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.1.0]hexanyl, 2-azabicyclo[2.1.1]hexanyl, 1- azabicyclo[2.2.1]heptanyl, 2-azabicyclo[2.2.1]heptanyl, 3-azabicyclo[3.2.0]heptanyl, bicyclo[1.1.1]pentanyl, octahydrocyclopenta[c]pyrrolyl, decahydro-1,6-naphthyridinyl, octahydro-1H-pyrrolo[3,4-c]pyridinyl, decahydro-2,7-naphthyridinyl), each substituted with 0, 1, 2, 3, 4 or 5 instances of R ⁶ . [0475] In some embodiments, R ³ is a 5-10 membered bicyclic heterocyclyl (e.g., decahydro-1,6-naphthyridinyl, 2-azaspiro[3.3]heptanyl, 5-oxa-2,8-diazaspiro[3.5]nonanyl, 8- azabicyclo[3.2.1]octanyl, 2-azabicyclo[2.2.2]octanyl, 3-azabicyclo[3.2.0]heptanyl, 3- azabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.1.0]hexanyl, 2-azabicyclo[2.1.1]hexanyl, 1- azabicyclo[2.2.1]heptanyl, 3-azabicyclo[3.2.0]heptanyl, bicyclo[1.1.1]pentanyl, octahydrocyclopenta[c]pyrrolyl, decahydro-1,6-naphthyridinyl, octahydro-1H-pyrrolo[3,4- c]pyridinyl, decahydro-2,7-naphthyridinyl), each substituted with 0, 1, 2, 3, 4 or 5 instances of R ⁶ . [0476] In some embodiments, R ³ is selected from the group consisting of decahydro-1,6- naphthyridinyl, 2-azaspiro[3.3]heptanyl, 5-oxa-2,8-diazaspiro[3.5]nonanyl, 8- azabicyclo[3.2.1]octanyl, 2-azabicyclo[2.2.2]octanyl, 3-azabicyclo[3.2.0]heptanyl, 3- azabicyclo[3.1.1]heptanyl, 3-azabicyclo[3.1.0]hexanyl, 2-azabicyclo[2.1.1]hexanyl, 1- azabicyclo[2.2.1]heptanyl, 3-azabicyclo[3.2.0]heptanyl, bicyclo[1.1.1]pentanyl, octahydrocyclopenta[c]pyrrolyl, decahydro-1,6-naphthyridinyl, octahydro-1H-pyrrolo[3,4- c]pyridinyl and decahydro-2,7-naphthyridinyl, each substituted with 0, 1, 2, 3, 4 or 5 instances of R ⁶ . [0477] In some embodiments, R ³ is selected from the group consisting of 2- azaspiro[3.3]heptanyl, 2-azabicyclo[2.2.2]octanyl, 1-azabicyclo[2.2.1]heptanyl, and 2- azabicyclo[2.2.1]heptanyl each substituted with 0 or 1 instances of R ⁶ . [0478] In some embodiments, R ³ is selected from the group consisting of 2- azaspiro[3.3]heptanyl, 2-azabicyclo[2.2.2]octanyl and 1-azabicyclo[2.2.1]heptanyl. [0479] In some embodiments, R ³ is selected from the group consisting of decahydro-1,6- naphthyridin-6-yl, 2-azaspiro[3.3]heptan-6-yl, 5-oxa-2,8-diazaspiro[3.5]nonan-8-yl, 8- azabicyclo[3.2.1]octan-3-yl, 2-azabicyclo[2.2.2]octan-4-yl, 3-azabicyclo[3.2.0]heptan-6-yl, 3-azabicyclo[3.1.1]heptan-1-yl, 3-azabicyclo[3.1.0]hexan-6-yl, 1-azabicyclo[2.2.1]heptan-4- yl, 2-azabicyclo[2.2.1]heptan-4-yl, 3-azabicyclo[3.2.0]heptan-6-yl, 2-azabicyclo[2.1.1]hexan- 4-yl, bicyclo[1.1.1]pentan-2-yl, octahydrocyclopenta[c]pyrrol-5-yl, decahydro-1,6- naphthyridin-6-yl, octahydro-1H-pyrrolo[3,4-c]pyridine-5-yl and decahydro-2,7- naphthyridin-2-yl. [0480] In some embodiments, R ³ is selected from the group consisting of decahydro-1,6- naphthyridin-6-yl, 2-azaspiro[3.3]heptan-6-yl, 5-oxa-2,8-diazaspiro[3.5]nonan-8-yl, 8- azabicyclo[3.2.1]octan-3-yl, 2-azabicyclo[2.2.2]octan-4-yl, 3-azabicyclo[3.2.0]heptan-6-yl, 3-azabicyclo[3.1.1]heptan-1-yl, 3-azabicyclo[3.1.0]hexan-6-yl, 1-azabicyclo[2.2.1]heptan-4- yl, 3-azabicyclo[3.2.0]heptan-6-yl, 2-azabicyclo[2.1.1]hexan-4-yl, bicyclo[1.1.1]pentan-2- yl, octahydrocyclopenta[c]pyrrol-5-yl, decahydro-1,6-naphthyridin-6-yl, octahydro-1H- pyrrolo[3,4-c]pyridine-5-yl and decahydro-2,7-naphthyridin-2-yl. [0481] In some embodiments, R ³ is selected from the group consisting of 2- azabicyclo[2.2.2]octan-4-yl, 2-azaspiro[3.3]heptan-6-yl, 2-azabicyclo[2.2.1]heptan-4-yl and 1-azabicyclo[2.2.1]heptan-4-yl. [0482] In some embodiments, R ³ is selected from the group consisting of 2- azabicyclo[2.2.2]octan-4-yl, 2-azaspiro[3.3]heptan-6-yl and 1-azabicyclo[2.2.1]heptan-4-yl. [0483] In some embodiments, R ³ is decahydro-1,6-naphthyridinyl. In some embodiments, R ³ is 2-azaspiro[3.3]heptanyl. In some embodiments, R ³ is 5-oxa-2,8- diazaspiro[3.5]nonanyl. In some embodiments, R ³ is 8-azabicyclo[3.2.1]octanyl. In some embodiments, R ³ is 2-azabicyclo[2.2.2]octanyl. In some embodiments, R ³ is 3- azabicyclo[3.2.0]heptanyl. In some embodiments, R ³ is 3-azabicyclo[3.1.1]heptanyl. In some embodiments, R ³ is 3-azabicyclo[3.1.0]hexanyl. In some embodiments, R ³ is 2- azabicyclo[2.1.1]hexanyl. In some embodiments, R ³ is 1-azabicyclo[2.2.1]heptanyl. In some embodiments, R ³ is 2-azabicyclo[2.2.1]heptanyl. In some embodiments, R ³ is 3- azabicyclo[3.2.0]heptanyl. In some embodiments, R ³ is bicyclo[1.1.1]pentanyl. In some embodiments, R ³ is octahydrocyclopenta[c]pyrrolyl. In some embodiments, R ³ is decahydro- 1,6-naphthyridinyl. In some embodiments, R ³ is octahydro-1H-pyrrolo[3,4-c]pyridinyl. In some embodiments, R ³ is decahydro-2,7-naphthyridinyl. [0484] In some embodiments, R ³ is decahydro-1,6-naphthyridin-6-yl. In some embodiments, R ³ is 2-azaspiro[3.3]heptan-6-yl. In some embodiments, R ³ is 5-oxa-2,8- diazaspiro[3.5]nonan-8-yl. In some embodiments, R ³ is 8-azabicyclo[3.2.1]octan-3-yl. In some embodiments, R ³ is 2-azabicyclo[2.2.2]octan-4-yl. In some embodiments, R ³ is 3- azabicyclo[3.2.0]heptan-6-yl. In some embodiments, R ³ is 3-azabicyclo[3.1.1]heptan-1-yl. In some embodiments, R ³ is 3-azabicyclo[3.1.0]hexan-6-yl. In some embodiments, R ³ is 1- azabicyclo[2.2.1]heptan-4-yl. In some embodiments, R ³ is 2-azabicyclo[2.2.1]heptan-4-yl. In some embodiments, R ³ is 3-azabicyclo[3.2.0]heptan-6-yl. In some embodiments, R ³ is 2- azabicyclo[2.1.1]hexan-4-yl. In some embodiments, R ³ is bicyclo[1.1.1]pentan-2-yl. In some embodiments, R ³ is octahydrocyclopenta[c]pyrrol-5-yl. In some embodiments, R ³ is decahydro-1,6-naphthyridin-6-yl. In some embodiments, R ³ is octahydro-1H-pyrrolo[3,4- c]pyridine-5-yl. In some embodiments, R ³ is decahydro-2,7-naphthyridin-2-yl. [0485] In some embodiments, R ³ is [0486] In some embodiments, the heterocyclyl is substituted with 0, 1, 2, 3, 4 or 5 instances of –D, =O, –Me, –CD ₃ , –Et, –C(=O)CH ₃ cyclopropyl, oxetan-3-yl, –OH, –N(CH ₃ ) ₂ , – CH ₂ N(CH ₃ ) ₂ or –C(=O)NHCH ₃ . In some embodiments, the heterocyclyl is substituted with 0, 1, 2, 3, 4 or 5 instances of –Me, –CD3, –Et, cyclopropyl, oxetan-3-yl, –OH, =O, –N(CH ₃ ) ₂ and –CH ₂ N(CH ₃ ) ₂ . [0487] In some embodiments, R ³ is monocyclic heterocyclylalkyl (e.g., oxetanylmethyl, aziridinylmethyl, tetrahydrofuranylmethyl, pyrrolidinylmethyl, pyrrolidinylethyl, pyrrolidinylpropyl, –CH(CH ₃ )CH ₂ -pyrrolidinyl, tetrahydropyranylmethyl, piperidinylmethyl, piperazinylmethyl, morpholinylmethyl, azepanylmethyl). In some embodiments, R ³ is selected from the group consisting of –CH ₂ -oxetan-3-yl, –CH ₂ -piperidin-4-yl, –CH ₂ - pyrrolidin-1-yl, –(CH ₂ ) ₂ -pyrrolidin-1-yl, –CH(CH ₃ )CH ₂ -pyrrolidin-1-yl. In some embodiments, R ³ is selected from the group consisting of –CH ₂ -piperidin-4-yl, –CH ₂ - pyrrolidin-1-yl, –(CH ₂ ) ₂ -pyrrolidin-1-yl, –CH(CH ₃ )CH ₂ -pyrrolidin-1-yl. In some embodiments, R ³ is selected from the group consisting of –CH ₂ -piperidin-4-yl, –CH ₂ - pyrrolidin-1-yl, –(CH ₂ ) ₂ -pyrrolidin-1-yl, –CH(CH ₃ )CH ₂ -pyrrolidin-1-yl. [0488] In some embodiments, R ³ is –CH ₂ -morpholin-4-yl. In some embodiments, R ³ is – (CH ₂ ) ₂ -morpholin-4-yl. In some embodiments, R ³ is –CH ₂ -oxetan-3-yl. In some embodiments, R ³ is –CH ₂ -piperidin-4-yl. In some embodiments, R ³ is –CH ₂ -pyrrolidin-1-yl. In some embodiments, R ³ is –(CH ₂ ) ₂ -pyrrolidin-1-yl. In some embodiments, R ³ is – CH(CH ₃ )CH ₂ -pyrrolidin-1-yl. In some embodiments, the monocyclic heterocyclylalkyl is unsubstitued. In some embodiments, the monocyclic heterocyclylalkyl e.g., substituted with 0, 1, 2, 3, 4, or 5 instances of R ⁶ , wherein R ⁶ is as described herein. In some embodiments, the monocyclic heterocyclylalkyl is substituted with 0, 1 or 2 instances of –Me. In some embodiments R ³ is cycloalkylalkyl (e.g., cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl). In some embodiments, R ³ is cyclopropylmethyl. [0489] In some embodiments, R ³ is a 5-10 membered heteroaryl (e.g., a 5-6 membered monocyclic heteroaryl or an 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from the group consisting of N, O and S). In some embodiments, R ³ is a 5-6 membered monocyclic heteroaryl (e.g., a 5-membered monocyclic heteroaryl containing 1-3 heteroatoms selected from the group consisting of O, N and S, a 6-membered monocyclic heteroaryl containing 1-3 N heteroatoms). In some embodiments, R ³ is a 5-membered monocyclic heteroaryl (e.g., pyrazolyl, pyrrolyl, thiophenyl, furyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, triazolyl, thiadiazolyl, oxadiazolyl). In some embodiments, R ³ is thiophenyl (e.g., thiophen-2-yl, thiophen-3-yl). In some embodiments, R ³ is pyrazolyl (e.g., pyrazol-1-yl, pyrazol-3-yl, pyrazol-5-yl). In some embodiments, R ³ is thiazolyl (e.g., thiazol-2-yl, thiazol-4-yl, thiazol-5-yl). In some embodiments, R ³ is a 6-membered monocyclic heteroaryl (e.g., pyridyl, pyrimidinyl, triazinyl, pyrazinyl, pyridazinyl). In some embodiments, R ³ is pyridinyl (e.g., pyridin-2-yl, pyridin-3-yl, pyridin-4-yl). In some embodiments, R ³ is pyrimidinyl (e.g, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl). In some embodiments, the heteroaryl is substituted with 0, 1, 2, 3, 4 or 5 instances of R ⁶ as defined in any of the embodiments described herein. [0490] In some embodiments, R ³ is a 6-10 membered mono or bicyclic aryl. In some embodiments, R ³ is phenyl. In some embodiments, the phenyl is substituted with 0, 1, 2, 3, 4 or 5 instances of R ⁶ as defined in any of the embodiments described herein. [0491] In some embodiments, R ³ is arylalkyl. In some embodiments, R ³ is benzyl. [0492] In some embodiments, R ³ is heteroarylalkyl (e.g., pyridinylmethyl, thiazolylmethyl, triazolylmethyl, pyrazolylmethyl). [0493] In some embodiments, R ³ is –OR ^a3 (e.g., hydroxy (–OH), methoxy, difluoromethoxy (–OCHF ₂ ), trifluoromethoxy (–OCF ₃ ), ethoxy, propoxy, isopropoxy, cyclopropyloxy, cyclobutyloxy, –O(CH ₂ ) ₂ N(CH ₃ ) ₂ , –O-tetrahydrofuran-3-yl, –O-tetrahydropyran-4-yl, –O(N- methyl piperidin-4-yl), –O-(N-Me-2-oxo-pyrrolidin-3-yl), –OCH ₂ CH(CH ₃ )N(CH ₃ ) ₂ , – OCH ₂ (N-Methylpyrrolidin-2-yl), –O(N-methyl piperidin-4-yl), –O-(CH ₂ ) ₂ -pyrrolidin-2-yl, – O-CH ₂ -piperidin-4-yl, –O-CH ₂ -oxetan-3-yl). In some embodiments, R ³ is hydroxy. In some embodiments, R ³ is methoxy. In some embodiments, R ³ is difluoromethoxy (–OCHF ₂ ). In some embodiments, R ³ is trifluoromethoxy (–OCF ₃ ). In some embodiments, R ³ is ethoxy. In some embodiments, R ³ is propoxy. In some embodiments, R ³ is isopropoxy. In some embodiments, R ³ is cyclopropyloxy. In some embodiments, R ³ is cyclobutyloxy. In some embodiments, R ³ is –O(CH ₂ ) ₂ N(CH ₃ ) ₂ . In some embodiments, R ³ is –O-tetrahydrofuran-3- yl. In some embodiments, R ³ is –O-tetrahydropyran-4-yl. In some embodiments, R ³ is – O(N-methyl piperidin-4-yl). In some embodiments, R ³ is –OCH ₂ (N-Methylpyrrolidin-2-yl). In some embodiments, R ³ is –O-(N-Me-2-oxo-pyrrolidin-3-yl). In some embodiments, R ³ is –O-(CH ₂ ) ₂ -pyrrolidin-2-yl. In some embodiments, R ³ is –O-CH ₂ -piperidin-4-yl. In some embodiments, R ³ is –O-CH ₂ -oxetan-3-yl. [0494] In some embodiments, R ³ is hydroxy. In some embodiments, R ³ is methoxy. In some embodiments, R ³ is ethoxy. In some embodiments, R ³ is propoxy. In some embodiments, R ³ is isopropoxy. In some embodiments R ³ is difluoromethoxy. (–OCHF ₂ ). In some embodiments, R ³ is trifluoromethoxy (–OCF ₃ ). In some embodiments, R ³ is – O(CH ₂ ) ₂ N(CH ₃ ) ₂ . [0495] In some embodiments, R ³ is –N(R ^a3 ) ₂ wherein R ^a3 is as described herein (e.g., –NH ₂ , –NHR ^a3 , –N(CH ₃ )R ^a3 ). In some embodiments, R ³ is –NH ₂ . In some embodiments, R ³ is – NHR ^a3 (e.g., –NHCH ₃ , –NHCH ₂ CH ₃ , –NHPr, –NHCH ₂ CF ₃ , –NH ⁱ Pr, –NHcyclopropyl, – NHcyclobutyl). In some embodiments, R ³ is NHCH ₂ CF ₃ . In some embodiments, R ³ is – N(CH ₃ )R ^a3 (e.g., –N(CH ₃ ) ₂ , –N(CH ₃ )CH ₂ CH ₃ , –N(CH ₂ CH ₃ ) ₂ , –N(CH ₃ )CH ₂ CH ₂ CH ₃ , – N(CH ₃ ) ⁱ Pr, –N(CH ₃ )cyclopropyl, –N(CH ₃ )cyclobutyl). [0496] In some embodiments, R ³ is –C(=O)R ^a3 or –C(=O)OR ^a3 wherein R ^a3 is as described herein. In some embodiments, R ³ is –C(=O)R ^a3 wherein R ^a3 is as described herein. In some embodiments, R ³ is –C(=O)alkyl. In some embodiments, R ³ is –C(=O)CH ₃ , – C(=O)cyclopropyl, –C(=O)cyclobutyl, –C(=O) ^t Bu, –C(=O) ⁱ Pr, –C(=O)CH ₂ CH ₂ CH ₃ , – C(=O)OCH ₃ or –C(O)CH ₂ CH ₂ N(CH ₃ ) ₂ . In some embodiments, R ³ is acetyl (–C(=O)CH ₃ ). In some embodiments, R ³ is –C(=O)CH ₂ CH ₂ N(CH ₃ ) ₂ . In some embodiments, R ³ is – C(=O)OR ^a3 . In some embodiments, R ³ is –COOH. In some embodiments, R ³ is COOCH ₃ . [0497] In some embodiments, R ³ is –NR ^a3 C(=O)R ^a3 wherein R ^a3 is as described herein. In certain embodiments, R ³ is ––NHC(=O)R ^a3 (e.g., –NHC(=O)CH ₃ , –NHC(=O)CH ₂ CH ₃ , – NHC(=O)CH ₂ CH ₂ CH ₃ , –NHC(=O) ⁱ Pr, –NHC(=O)Bu, –NHC(=O) ^t Bu, – NHC(=O)Cyclopropyl, –NHC(=O)Cyclobutyl, –C(O)CH ₂ CH ₂ N(CH ₃ ) ₂ .). In some embodiments, R ³ is –NHC(=O)CH ₃ . In some embodiments, R ³ is –C(O)CH ₂ CH ₂ N(CH ₃ ) ₂ . [0498] In some embodiments, R ³ is –N(CH ₃ )C(=O)R ^a3 wherein R ^a3 is as described herein (e.g., –N(CH ₃ )C(=O)CH ₃ , –N(CH ₃ )C(=O)CH ₂ CH ₃ , –N(CH ₃ )C(=O)CH ₂ CH ₂ CH ₃ , – N(CH ₃ )C(=O) ⁱ Pr, –N(CH ₃ )C(=O)Bu, –N(CH ₃ )C(=O) ^t Bu, –N(CH ₃ )C(=O)Cyclopropyl, – N(CH ₃ )C(=O)Cyclobutyl). [0499] In some embodiments, R ³ is –NR ^a3 C(=O)OR ^a3 wherein R ^a3 is as described herein. In certain embodiments, R ³ is –NHC(=O)OR ^a3 (e.g., –NHC(=O)OCH ₃ , – NHC(=O)OCH ₂ CH ₃ , –NHC(=O)OCH ₂ CH ₂ CH ₃ , –NHC(=O)O ⁱ Pr, –NHC(=O)OBu, – NHC(=O)O ^t Bu, –NHC(=O)OCyclopropyl, –NHC(=O)OCyclobutyl). In some embodiments, R ³ is –N(CH ₃ )C(=O)OR ^a3 (e.g., –N(CH ₃ )C(=O)OCH ₃ , –N(CH ₃ )C(=O)OCH ₂ CH ₃ , – N(CH ₃ )C(=O)OCH ₂ CH ₂ CH ₃ , –N(CH ₃ )C(=O)O ⁱ Pr, –N(CH ₃ )C(=O)OBu, – N(CH ₃ )C(=O)O ^t Bu, –N(CH ₃ )C(=O)OCyclopropyl, –N(CH ₃ )C(=O)OCyclobutyl). [0500] In some embodiments, R ³ is –C(=O)N(R ^a3 ) ₂ wherein R ^a3 is as described herein (e.g., –C(=O)NH ₂ , –C(=O)NHR ^a3 , –C(=O)N(CH ₃ )R ^a3 ). In some embodiments, R ³ is –C(=O)NH ₂ . In certain embodiments, R ³ is –C(=O)NHR ^a3 (e.g., –C(=O)NHCH ₃ , –C(=O)NHCH ₂ CH ₃ , – C(=O)NHPr, –C(=O)NH ⁱ Pr, –C(=O)NHBu, –C(=O)NH ^t Bu, –C(=O)NHCyclopropyl, – C(=O)NHCyclobutyl). In some embodiments, R ³ is –C(=O)NHCH ₃ . In certain embodiments, R ³ is –C(=O)N(CH ₃ )R ^a3 (e.g., –C(=O)N(CH ₃ ) ₂ , –C(=O)N(CH ₃ )CH ₂ CH ₃ , – C(=O)N(CH ₃ )CH ₂ CH ₂ CH ₃ , –C(=O)N(CH ₃ ) ⁱ Pr, –C(=O)N(CH ₃ )Bu, –C(=O)N(CH ₃ ) ^t Bu, – C(=O)N(CH ₃ )Cyclopropyl, –C(=O)N(CH ₃ )Cyclobutyl). [0501] In some embodiments, R ³ is –OC(=O)N(R ^a3 ) ₂ wherein R ^a3 is as described herein. In certain embodiments, R ³ is –OC(=O)NHR ^a3 (e.g., –OC(=O)NHCH ₃ , –OC(=O)NHCH ₂ CH ₃ , – OC(=O)NHPr, –OC(=O)NH ⁱ Pr, –OC(=O)NHBu, –OC(=O)NH ^t Bu, – OC(=O)NHCyclopropyl, –OC(=O)NHCyclobutyl). In certain embodiments, R ³ is – OC(=O)N(CH ₃ )R ^a3 (e.g., –OC(=O)N(CH ₃ ) ₂ , –OC(=O)N(CH ₃ )CH ₂ CH ₃ , – OC(=O)N(CH ₃ )CH ₂ CH ₂ CH ₃ , –OC(=O)N(CH ₃ ) ⁱ Pr, –OC(=O)N(CH ₃ )Bu, – OC(=O)N(CH ₃ ) ^t Bu, –OC(=O)N(CH ₃ )Cyclopropyl, –OC(=O)N(CH ₃ )Cyclobutyl). [0502] In some embodiments, R ³ is –OC(=O)R ^a3 wherein R ^a3 is as described herein. (e.g., –OC(=O)CH ₃ , –OC(=O)CH ₂ CH ₃ , –OC(=O)CH ₂ CH ₂ CH ₃ , –OC(=O)CH ₂ CH ₂ CH ₃ , – OC(=O)Bu, –OC(=O)Bu, –OC(=O)Cyclopropyl, –OC(=O)Cyclobutyl). In some embodiments, R ³ is –OC(=O)CH ₃ . [0503] In some embodiments, R ³ is –S(=O)R ^a3 wherein R ^a3 is as described herein. In certain embodiments, R ³ is –S(=O)alkyl (e.g., –S(=O)CH ₃ , –S(=O)CH ₂ CH ₃ , – S(=O)CH ₂ CH ₂ CH ₃ , –S(=O) ⁱ Pr). In some embodiments R ³ is –S(=O)CH ₃ . In certain embodiments, R ³ is –S(=O)cycloalkyl (e.g., –S(=O)cyclopropyl, –S(=O)cyclobutyl, – S(=O)cyclopentyl, –S(=O)cyclohexyl). [0504] In some embodiments, R ³ is –S(=O) ₂ R ^a3 wherein R ^a3 is as described herein. In certain embodiments, R ³ is –S(=O) ₂ alkyl (e.g., –S(=O) ₂ CH ₃ , –S(=O) ₂ CH ₂ CH ₃ , –S(=O) ₂ Pr, – S(=O) ₂ ⁱ Pr). In some embodiments R ³ is –S(=O) ₂ CH ₃ . In certain embodiments, R ³ is – S(=O) ₂ cycloalkyl (e.g., –S(=O) ₂ cyclopropyl, –S(=O) ₂ cyclobutyl, –S(=O) ₂ cyclopentyl, – S(=O) ₂ cyclohexyl). In some embodiments, R ³ is S(=O) ₂ aryl (e.g., –S(=O) ₂ phenyl). [0505] In some embodiments, R ³ is –SR ^a3 wherein R ^a3 is as described herein. In certain embodiments, R ³ is –Salkyl (e.g., –SCH ₃ , –SCH ₂ CH ₃ , –SPr, –S ⁱ Pr). In certain embodiments, R ³ is –Scycloalkyl (e.g., –Scyclopropyl, –Scyclobutyl, –Scyclopentyl, –Scyclohexyl). In certain embodiments, R ³ is –Saryl (e.g., –Sphenyl). [0506] In some embodiments, R ³ is –S(=O)(=NR ^a3 )R ^a3 wherein R ^a3 is as described herein. In certain embodiments, R ³ is –S(=O)(=NH)R ^a3 (e.g., –S(=O)(=NH)CH ₃ , – S(=O)(=NH)CH ₂ CH ₃ , –S(=O)(=NH)CH ₂ CH ₂ CH ₃ , –S(=O)(=NH) ⁱ Pr, –S(=O)(=NH)Bu, – S(=O)(=NH) ^t Bu, –S(=O)(=NH)Cyclopropyl, –S(=O)(=NH)Cyclobutyl). In some embodiments, R ³ is –S(=O)(=NCH ₃ )R ^a3 (e.g., –S(=O)(=NCH ₃ )CH ₃ , – S(=O)(=NCH ₃ )CH ₂ CH ₃ , –S(=O)(=NCH ₃ )CH ₂ CH ₂ CH ₃ , –S(=O)(=NCH ₃ ) ⁱ Pr, – S(=O)(=NCH ₃ )Bu, –S(=O)(=NCH ₃ ) ^t Bu, –S(=O)(=NCH ₃ )Cyclopropyl, – S(=O)(=NCH ₃ )Cyclobutyl). [0507] In some embodiments, R ³ is –NR ^a3 S(=O) ₂ R ^a3 wherein R ^a3 is as described herein. In certain embodiments, R ³ is –NHS(=O) ₂ alkyl (e.g., –NHS(=O) ₂ CH ₃ , –NHS(=O) ₂ CH ₂ CH ₃ , – NHS(=O) ₂ Pr, –NHS(=O) ₂ ⁱ Pr). In certain embodiments, R ³ is –NHS(=O) ₂ cycloalkyl (e.g., – NHS(=O) ₂ cyclopropyl, –NHS(=O) ₂ cyclobutyl, –NHS(=O) ₂ cyclopentyl, – NHS(=O) ₂ cyclohexyl). In certain embodiments, R ³ is –N(CH ₃ )S(=O) ₂ alkyl (e.g., – N(CH ₃ )S(=O) ₂ CH ₃ , –N(CH ₃ )S(=O) ₂ CH ₂ CH ₃ , –N(CH ₃ )S(=O) ₂ Pr, –N(CH ₃ )S(=O) ₂ ⁱ Pr). In certain embodiments, R ³ is –N(CH ₃ )S(=O) ₂ cycloalkyl (e.g., –N(CH ₃ )S(=O) ₂ cyclopropyl, – N(CH ₃ )S(=O) ₂ cyclobutyl, –N(CH ₃ )S(=O) ₂ cyclopentyl, –N(CH ₃ )S(=O) ₂ cyclohexyl). [0508] In some embodiments, R ³ is –S(=O) ₂ N(R ^a3 ) ₂ wherein R ^a3 is as described herein. (e.g., –S(=O) ₂ NH ₂ , –S(=O) ₂ NHR ^a3 , –S(=O) ₂ N(CH ₃ )R ^a3 ). In some embodiments, R ³ is – S(=O) ₂ NH ₂ . In some embodiments, R ³ is –S(=O) ₂ NHR ^a3 (e.g., –S(=O) ₂ NHCH ₃ , – S(=O) ₂ NHCH ₂ CH ₃ , –S(=O) ₂ NHPr, –S(=O) ₂ NH ⁱ Pr, –S(=O) ₂ NHcyclopropyl, – S(=O) ₂ NHcyclobutyl). In some embodiments, R ³ is –S(=O) ₂ N(CH ₃ )R ^a3 (e.g., – S(=O) ₂ N(CH ₃ ) ₂ , –S(=O) ₂ N(CH ₃ )CH ₂ CH ₃ , –S(=O) ₂ N(CH ₃ )CH ₂ CH ₂ CH ₃ , –S(=O) ₂ N(CH ₃ ) ⁱ Pr, –S(=O) ₂ N(CH ₃ )cyclopropyl, –S(=O) ₂ N(CH ₃ )cyclobutyl). [0509] As generally defined herein, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently selected from the group consisting of H, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, C6-C ₁₀ aryl, 5-10 membered heteroaryl, arylalkyl and heteroarylalkyl wherein each alkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is optionally substituted at any available position (e.g., substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is as defined in any of the embodiments described herein). [0510] In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently unsubstituted. In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently substituted with 1 instance of R ⁵ . In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently substituted with 2 instances of R ⁵ . In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently substituted with 3 instances of R ⁵ . [0511] In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently selected from the group consisting of H, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ haloalkyl, –C ₁ –C ₆ heteroalkyl substituted with 0 or 1 instances of =O, C ₃ –C ₉ cycloalkyl, and 3-10 membered heterocyclyl substituted with 0 or 1 instances of =O, –Me or a combination thereof. [0512] In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently selected from the group consisting of H, –C ₁ –C ₆ alkyl, (e.g., –Me, –Et, –Pr, – ⁱ Pr, –sec-Bu, – ^t Bu), –C ₁ –C ₆ haloalkyl (e.g., –CF ₃ , –CHF ₂ , –CH ₂ CF ₃ ) and –C ₁ –C ₆ heteroalkyl substituted with 0 or 1 instances of =O (e.g., –CH ₂ CH ₂ N(CH ₃ ) ₂ , –CH ₂ C(=O)N(CH ₃ ) ₂ , –CH(CH ₃ )CH ₂ N(CH ₃ ) ₂ , – CH(CH ₃ )C(=O)N(CH ₃ ) ₂ ). [0513] In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently selected from the group consisting of H, –Me, –Et, –Pr, – ⁱ Pr, –sec-Bu, – ^t Bu, –CF ₃ , –CHF ₂ , –CH ₂ CF ₃ and – CH ₂ CH ₂ N(CH ₃ ) ₂ . [0514] In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently selected from the group consisting of H, –C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu) and –C ₁ –C ₆ haloalkyl (e.g., –CHF ₂ , –CF ₃ ). In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently selected from the group consisting of H and –C ₁ –C ₆ alkyl (e.g., –Me, –Et, – Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu). [0515] In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently H. [0516] In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently –C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu). In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently –Me. In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently –Et. In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently –Pr or – ⁱ Pr. [0517] In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently –C ₁ –C ₆ heteroalkyl. In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently methoxymethyl (–CH ₂ OCH ₃ ). In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently hydroxymethyl (–CH ₂ OH). In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently aminomethyl (e.g.,–CH ₂ NH ₂ , –CH ₂ NHCH ₃ , –CH ₂ N(CH ₃ ) ₂ , – CH ₂ CH ₂ N(CH ₃ ) ₂ ). In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently – CH ₂ CH ₂ N(CH ₃ ) ₂ ). [0518] In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently –C ₁ –C ₆ haloalkyl. In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently trifluoromethyl (–CF ₃ ). In other embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently difluoromethyl (–CHF ₂ ). [0519] In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl). In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently cyclopropyl. In some embodiments each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently cyclobutyl. In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently cyclopentyl. In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently cyclohexyl. In some embodiments, the cycloalkyl is substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is as defined in any of the embodiments described herein. [0520] In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently 3-10 membered heterocyclyl (e.g., oxetanyl, tetrahydropyranyl, tetrahydrofuranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl). In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently is oxetanyl. In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently tetrahydropyranyl. In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently tetrahydrofuranyl. In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently azetidinyl. In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently pyrrolidinyl. In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently piperidinyl. In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently piperazinyl. In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently morpholinyl. In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently azepanyl. In some embodiments, each heterocyclyl is substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is as defined in any of the embodiments described herein. [0521] In some embodiments, R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently a 5-10 membered heteroaryl (e.g., a 5-6 membered monocyclic heteroaryl or an 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms independently selected from the group consisting of N, O and S). In some embodiments, R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently a 5-6 membered monocyclic heteroaryl (e.g., a 5-membered monocyclic heteroaryl containing 1-3 heteroatoms independently selected from the group consisting of O, N and S, a 6-membered monocyclic heteroaryl containing 1-3 N heteroatoms). In some embodiments, R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently a 5-membered monocyclic heteroaryl (e.g., pyrazolyl, pyrrolyl, thiophenyl, furyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, triazolyl, thiadiazolyl, oxadiazolyl). In some embodiments, R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently thiophenyl (e.g., thiophen-2-yl, thiophen-3-yl). In some embodiments, R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently pyrazolyl (e.g., pyrazol-1-yl, pyrazol-3-yl, pyrazol-5-yl). In some embodiments, R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently thiazolyl (e.g., thiazol-2-yl, thiazol-4-yl, thiazol-5-yl). In some embodiments, R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently a 6-membered monocyclic heteroaryl (e.g., pyridyl, pyrimidinyl, triazinyl, pyrazinyl, pyridazinyl). In some embodiments, R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently pyridinyl (e.g., pyridin-2-yl, pyridin-3- yl, pyridin-4-yl). In some embodiments, R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently pyrimidinyl (e.g, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl). In some embodiments, the heteroaryl is substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is as defined in any of the embodiments described herein. [0522] In some embodiments, R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently C ₆ -C ₁₀ aryl. In some embodiments, R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently 6-10 membered mono or bicyclic aryl. In some embodiments, R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently phenyl. In some embodiments, the phenyl is substituted with 0, 1, 2 or 3 instances of R ⁵ as defined in any of the embodiments described herein. In some embodiments, the aryl is substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is as defined in any of the embodiments described herein. [0523] In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently cycloalkylalkyl (e.g., cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl). In some embodiments, the cycloalkylalkyl is substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is as defined in any of the embodiments described herein. [0524] In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently heterocyclylalkyl (e.g., oxetanylmethyl, aziridinylmethyl, tetrahydrofuranylmethyl, pyrrolidinylmethyl, tetrahydropyranylmethyl, piperidinylmethyl, piperazinylmethyl, morpholinylmethyl, azepanylmethyl). In some embodiments, the heterocyclylalkyl is substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is as defined in any of the embodiments described herein. [0525] In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently arylalkyl. In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently benzyl. In some embodiments, the arylalkyl is substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is as defined in any of the embodiments described herein. [0526] In some embodiments, each R ^a1 , R ^a2 , R ^a3 and R ^a4 is independently heteroarylalkyl (e.g., pyridinylmethyl, thiazolylmethyl, triazolylmethyl, pyrazolylmethyl). In some embodiments, the heteroarylalkyl is substituted with 0, 1, 2 or 3 instances of R ⁵ , wherein each R ⁵ is as defined in any of the embodiments described herein. [0527] As generally defined herein, each R ⁵ is independently selected from the group consisting of =O, halo, –CN, –C ₁ –C ₆ alkyl, –C ₁ –C ₆ heteroalkyl, –C ₁ –C ₆ haloalkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, C ₆ –C ₁₀ aryl, 5-10 membered heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, –OR ^b , –N(R ^b ) ₂ , –C(=O)R ^b , – C(=O)OR ^b , –NR ^b C(=O)R ^b , –NR ^b C(=O)OR ^b , –C(=O)N(R ^b ) ₂ , –OC(=O)N(R ^b ) ₂ , –S(=O)R ^b , – S(=O) ₂ R ^b , –SR ^b , –S(=O)(=NR ^b )R ^b , –NR ^b S(=O) ₂ R ^b and –S(=O) ₂ N(R ^b ) ₂ , wherein each R ^b is independently selected from the group consisting of H, –C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu).and C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl). [0528] In some embodiments, each R ⁵ is independently selected from the group consisting of =O, halo, –CN, –C ₁ –C ₆ alkyl (e.g., –Me, –Et, –Pr, – ⁱ Pr,– ⁿ Bu, – ^t Bu, –sec-Bu, –iso-Bu), – C ₁ –C ₆ haloalkyl (e.g., –CF3, –CHF2), –C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl), 3-10 membered heterocyclyl (e.g., oxetanyl, tetrahydropyranyl, tetrahydrofuranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl), C ₆ –C ₁₀ aryl (e.g., phenyl), 5-10 membered heteroaryl (e.g., pyrazolyl, pyrrolyl, thiophenyl, furyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, triazolyl, thiadiazolyl, oxadiazolyl), cycloalkylalkyl (e.g., cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl), heterocyclylalkyl (e.g., oxetanylmethyl, aziridinylmethyl, tetrahydrofuranylmethyl, pyrrolidinylmethyl, tetrahydropyranylmethyl, piperidinylmethyl, piperazinylmethyl, morpholinylmethyl, azepanylmethyl), arylalkyl (e.g., benzyl), heteroarylalkyl (e.g., pyridinylmethyl, thiazolylmethyl, triazolylmethyl, pyrazolylmethyl), –OR ^b , –N(R ^b ) ₂ , –C(=O)R ^b , –C(=O)OR ^b , –NR ^b C(=O)R ^b , –NR ^b C(=O)OR ^b , –C(=O)N(R ^b ) ₂ , –OC(=O)N(R ^b ) ₂ , –S(=O)R ^b , –S(=O) ₂ R ^b , –SR ^b , –S(=O)(=NR ^b )R ^b , – NR ^b S(=O) ₂ R ^b and –S(=O) ₂ N(R ^b ) ₂ , wherein each R ^b is as defined in any of the embodiments described herein. In some embodiments, each R ^b is H or –Me. In some embodiments, R ⁵ is – Me. [0529] As generally defined herein, each R ⁶ is independently selected from the group consisting of –C ₁ –C ₆ alkyl, –C ₃ –C ₉ cycloalkyl, 3-10 membered heterocyclyl, –OH, =O, halo, –OC ₁ -C ₆ alkyl, –C ₁ –C ₆ haloalkyl, –C(=O)C ₁ -C ₆ alkyl, –N(C ₁ -C ₆ alkyl) ₂ , –C ₁ –C ₆ heteroalkyl, and –NHC(=O)C ₁ -C ₆ alkyl, wherein one or more hydrogens of the –C ₁ –C ₆ alkyl can be replaced with deuterium. [0530] In some embodiments, each R ⁶ is independently selected from the group consisting of –Me, –Et, – ⁱ Pr, –CD ₃ , cyclopropyl, oxetan-3-yl, –OH, =O, –F, –OCH ₃ , –CH ₂ CH ₂ F, – CH ₂ CHF ₂ , –CH ₂ CH ₂ CF ₃ , –C(=O)CH ₃ , –N(CH ₃ ) ₂ , –CH ₂ N(CH ₃ ) ₂ , –CH ₂ N(CH ₃ )CH ₂ CH ₃ , – N( ⁱ Pr)(CH ₂ CH ₃ ), –N( ⁱ Pr)(CH ₃ ), –N(CH ₂ CH ₃ ) ₂ , –N(CH ₃ )(CH ₂ CH ₃ ), –NHC(=O)CH ₃ ). [0531] In some embodiments, each R ⁶ is independently selected from the group consisting of –Me, –Et, –CD3, cyclopropyl, oxetan-3-yl, –OH, =O, –N(CH ₃ ) ₂ and –CH ₂ N(CH ₃ ) ₂ . [0532] In some embodiments, R ⁶ is =O. [0533] In certain embodiments, R ⁶ is halo (e.g., fluoro, chloro, bromo, iodo). In some embodiments, R ⁶ is –Cl. In some embodiments, R ⁶ is –F. In some embodiments, R ⁶ is –Br. In some embodiments, R ⁶ is –I. [0534] In certain embodiments, R ⁶ is –C ₁ –C ₆ alkyl. In some embodiments, one or more hydrogens of the –C ₁ –C ₆ alkyl can be replaced with deuterium. In some embodiments, R ⁶ is –Me. In some embodiments, R ⁶ is –CD ₃ . In some embodiments, R ⁶ is –Et. In some embodiments R ⁶ is –Pr or –iPr. [0535] In some embodiments, R ⁶ is C ₃ –C ₉ cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl). In some embodiments, R ⁶ is cyclopropyl. In some embodiments R ⁶ is cyclobutyl. In some embodiments, R ⁶ is cyclopentyl. In some embodiments, R ⁶ is cyclohexyl. [0536] In some embodiments, R ⁶ is 3-10 membered heterocyclyl (e.g., oxetanyl, tetrahydropyranyl, tetrahydrofuranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl). In some embodiments, R ⁶ is 3-6 membered heterocyclyl (e.g., oxetanyl, tetrahydropyranyl, tetrahydrofuranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl). In some embodiments, R ⁶ is oxetanyl (e.g., oxetan-3-yl). In some embodiments, R ⁶ is tetrahydropyranyl. In some embodiments, R ⁶ is tetrahydrofuranyl. In some embodiments, R ⁶ is azetidinyl. In some embodiments, R ⁶ is pyrrolidinyl. In some embodiments, R ⁶ is piperidinyl. In some embodiments, R ⁶ is piperazinyl. In some embodiments, R ⁶ is morpholinyl. In some embodiments, R ⁶ is azepanyl. [0537] In some embodiments, R ⁶ is OH. [0538] In some embodiments, R ⁶ is –OC ₁ -C ₆ alkyl (e.g., methoxy, ethoxy, propoxy, isopropoxy). In some embodiments, R ⁶ is methoxy. In some embodiments, R ⁶ is ethoxy. In some embodiments, R ⁶ is propoxy. In some embodiments, R ⁶ is isopropoxy. [0539] In some embodiments, R ⁶ is –C ₁ –C ₆ haloalkyl (e.g., –CF ₃ , –CHF ₂ , –CH ₂ F, – CH ₂ CF ₃ ). In some embodiments, R ⁶ is trifluoromethyl (–CF ₃ ). In other embodiments, R ⁶ is difluoromethyl (–CHF ₂ ). [0540] In some embodiments, R ⁶ is –C(=O)C ₁ -C ₆ alkyl (e.g., –C(=O)CH ₃ , –C(=O) ⁱ Pr, – C(=O)CH ₂ CH ₂ CH ₃ , –C(O) ⁱ Bu)). [0541] In some embodiments, R ⁶ is –N(C ₁ -C ₆ alkyl) ₂ (e.g., –N(CH ₃ ) ₂ , –N(CH ₃ )CH ₂ CH ₃ , – N(CH ₃ )CH ₂ CH ₂ CH ₃ , –N(CH ₃ ) ⁱ Pr). In some embodiments, R ⁶ is –N(CH ₃ ) ₂ . [0542] In some embodiments, R ⁶ is –C ₁ –C ₆ heteroalkyl. In some embodiments, R ⁶ is methoxymethyl (–CH ₂ OCH ₃ ). In some embodiments, R ⁶ is hydroxymethyl (–CH ₂ OH). In some embodiments, R ⁶ is aminomethyl (e.g.,–CH ₂ NH ₂ , –CH ₂ NHCH ₃ , –CH ₂ N(CH ₃ ) ₂ . [0543] In some embodiments, R ⁶ is –NHC(=O)C ₁ -C ₆ alkyl (e.g., –NHC(=O)CH ₃ , – NHC(=O)CH ₂ CH ₃ , –NHC(=O)CH ₂ CH ₂ CH ₃ , –NHC(=O) ⁱ Pr, –NHC(=O)Bu, –NHC(=O) ^t Bu). [0544] In one embodiment, provided is a compound selected from the compounds of Table 1, or pharmaceutically acceptable salts thereof. [0545] Compounds described herein (e.g., a compound of Formula (A) and Formula (I) to (III7a) or a compound of Table 1, or pharmaceutically acceptable salts thereof) are useful as inhibitors of PRMT5 (e.g., MTA uncompetitive PRMT5 inhibitors). [0546] Table 1 indicates IC ₅₀ and IC ₉₀ values in an MTAP-isogenic cell line pair for exemplary compounds in an SDMA in-cell western assay (described in Example 246) (columns 4-6). HAP1 MTAP-intact is a cell line in which endogenous levels of MTAP are expressed, and HAP1 MTAP-deleted is an MTAP-null cell line. For Table 1, “a” and “aa” indicates an IC ₅₀ of < 5 nM, “b” and “bb” indicates an IC ₅₀ equal to or greater than 5 nM but less than 50 nM, and “c” and “cc” indicates an IC ₅₀ of greater than or equal to 50 nM in the HAP1 MTAP-intact (column 4) and the HAP1 MTAP-deleted (column 5) assays, respectively. Similarly, “aaa” indicates an IC90 of < 75 nM, “bbb” indicates an IC90 equal to or greater than 75 nM but less than 125 nM, and “ccc” indicates an IC90 of greater than or equal to 125 nM in the HAP1 MTAP-deleted (column 6) assay. [0547] In column 7, “A” indicates an IC ₅₀ ratio greater than or equal to 30 fold between the IC ₅₀ in the HAP1 MTAP-intact cell line and the HAP1 MTAP-deleted cell line; “B” indicates an IC ₅₀ ratio greater than or equal to 15 fold but lower than 30 fold between the IC ₅₀ in the HAP1 MTAP-intact cell line and the HAP1 MTAP-deleted cell line; “C” indicates an IC ₅₀ ratio of less than 15 fold between the IC ₅₀ in the HAP1 MTAP-intact cell line and the HAP1 MTAP-deleted cell line. Compounds with a ratio in the SDMA in-cell western assay of equal to or greater than 3 fold are considered MTAP-selective. [0548] Table 1 additionally indicates IC ₅₀ values in a viability assay for the MTAP-deleted cell line (described in Example 247) (column 8), indicating the effect of treatment with compound on cell survival. In column 8, a value of A ^* indicates an IC ₅₀ of less than 100 nM, a value of B ^* indicates an IC ₅₀ equal to or greater than 100 nM but less than 1 μM, and a value of C ^* indicates an IC ₅₀ greater than or equal to 1 μM. [0549] Unless otherwise indicated, the absolute stereochemistry of all chiral atoms is as depicted. Compounds marked with (or) or (rel) are single enantiomers wherein the absolute stereochemistry was arbitrarily assigned (e.g., based on chiral SFC elution as described in the Examples section). Compounds marked with (and) or (rac) are mixtures of enantiomers wherein the relative stereochemistry is as shown. Compounds marked with (abs) are single enantiomers wherein the absolute stereochemistry is as indicated. In some instances, different indicators selected from (abs) (or) and (and) apply to different portions of the molecule. For example, compound 2 is described as “(abs) core piperidine, (or) R ³ pyrrolidine”. The “(abs) core piperidine” designation indicates that the absolute stereochemistry of the piperidine attached to the oxamide of Formula (I) is as depicted. The “(or) R ³ pyrrolidine” designation indicates that the stereochemistry on the pyrrolidine corresponding to R ³ of Formula (I) is either R or S (i.e., not a mixture of R and S), but the absolute configuration has been arbitrarily assigned.