SUBSTITUTED PIPERIDINES AND SUBSTITUTED TETRAHYDROPYRIDINES AS IMMUNE-MODULATING COMPOUNDS CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Patent Application No. 63/333,044, filed April 20, 2022, which is incorporated herein by reference in its entirety. BACKGROUND OF THE INVENTION [0002] Glutaminyl-peptide cyclotransferase like (QPCTL) protein has emerged as a potential target for cancer immunotherapy. The inhibition of QPCTL prevents formation of pyroglutamate on CD47 at the SIRPα binding site, therefore interfering with the critical CD47 signaling pathway. Genetic and pharmacological interference with QPCTL activity enhances antibody- dependent cellular phagocytosis and cellular cytotoxicity of tumor cells, and interference with QPCTL expression leads to an increase in neutrophil-mediated killing of tumor cells in vivo. Accordingly, QPCTL represents an attractive target for the treatment of conditions, diseases, or disorders that would benefit from modulating such activity, including cancer. SUMMARY OF THE INVENTION [0003] Compounds described herein are glutaminyl-peptide cyclotransferase like (QPCTL) protein modulator compounds. In some embodiments, the compounds described herein are glutaminyl-peptide cyclotransferase like (QPCTL) protein modulator compounds. In some embodiments, the compounds described herein are glutaminyl-peptide cyclotransferase like (QPCTL) protein antagonists. In some embodiments, the compounds described herein are glutaminyl-peptide cyclotransferase like (QPCTL) protein inhibitors. [0004] In one aspect, provided herein is a compound of Formula (A-1) Formula (A-1), or a pharmaceutically acceptable salt, or solvate thereof, wherein: X is O or NM ³ ; M ¹ , M ² , and M ³ are each independently hydrogen, unsubstituted or substituted C ₁ -C ₄ alkyl, unsubstituted or substituted C ₂ -C ₄ alkenyl, unsubstituted or substituted C ₂ -C ₄ alkynyl, unsubstituted or substituted C1-C4 fluoroalkyl, unsubstituted or substituted C3 cycloalkyl, or unsubstituted or substituted C1-C4 heteroalkyl; is a single bond or a double bond; Y ¹ is N or CR ¹ ; Y ² is N or CR ² ; Y ³ is N or CR ³ ; and Y ⁴ is N or CR ⁴ ; Z ¹ is N or CR ⁵ ; Z ² is N or CR ⁶ ; Z ³ is N or CR ⁷ ; Z ⁴ is N or CR ⁸ ; and Z ⁵ is N or CR ⁹ ; R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, -CN, - OR ¹⁰ , -CO2R ¹⁰ , -C(=O)N(R ¹⁰ )2, -N(R ¹⁰ )2, -NR ¹⁰ C(=O)R ¹¹ , -SR ¹⁰ , -S(=O)R ¹¹ , -SO2R ¹¹ , - SO2N(R ¹⁰ )2, or -N(R ¹⁰ )SO2R ¹¹ ; each R ¹⁰ is independently selected from hydrogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, and 4- to 6-membered heterocycloalkyl; or two R ¹⁰ on the same N atom are taken together with the N atom to which they are attached to form an unsubstituted or substituted N-containing 4- to 6-membered heterocycloalkyl; and each R ¹¹ is independently selected from unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, and 4- to 6-membered heterocycloalkyl; wherein each substituted alkyl, substituted alkenyl, substituted alkynyl, substituted fluoroalkyl, substituted heteroalkyl, substituted cycloalkyl, and substituted heterocycloalkyl is substituted with one or more R ^s groups independently selected from halogen, C1-C6 alkyl, monocyclic carbocycle, monocyclic heterocycle, -CN, -OR ¹² , - CO ₂ R ¹² , -C(=O)N(R ¹² ) ₂ , -N(R ¹² ) ₂ , -NR ¹² C(=O)R ¹³ , -SR ¹² , -S(=O)R ¹³ , -SO ₂ R ¹³ , - SO ₂ N(R ¹² ) ₂ , and -N(R ¹² )SO ₂ R ¹³ ; each R ¹² is independently selected from hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl and 6-membered heteroaryl; or two R ¹² groups are taken together with the N atom to which they are attached to form a N-containing 4- to 6-membered heterocycloalkyl; each R ¹³ is independently selected from C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl, and 6-membered heteroaryl; wherein 0, 1, or 2 of Y ¹ , Y ² , Y ³ , and Y ⁴ are N; wherein 0, 1, or 2 of Z ¹ , Z ² , Z ³ , Z ⁴ , and Z ⁵ are N; and wherein M is not . [0005] In some embodiments, the compound is a compound of Formula (A1-1): Formula (A1-1), or a pharmaceutically acceptable salt, or solvate thereof. [0006] In some embodiments, the compound is a compound of Formula (A2-1): Formula (A2-1), or a pharmaceutically acceptable salt, or solvate thereof. [0007] In some embodiments, the compound is a compound of Formula (B-1): or a pharmaceutically acceptable salt, or solvate thereof. [0008] In some embodiments, the compound is a compound of Formula (B1-1): or a pharmaceutically acceptable salt, or solvate thereof. [0009] In some embodiments, the compound is a compound of Formula (B2-1): Formula (B2-1), or a pharmaceutically acceptable salt, or solvate thereof. [0010] In some embodiments, the compound is a compound of Formula (C-1): Formula (C-1), or a pharmaceutically acceptable salt, or solvate thereof. [0011] In some embodiments, the compound is a compound of Formula (C1-1): or a pharmaceutically acceptable salt, or solvate thereof. [0012] In some embodiments, the compound is a compound of Formula (C2-1): or a pharmaceutically acceptable salt, or solvate thereof. [0013] In some embodiments, the compound is a compound of Formula (D-1): Formula (D-1), or a pharmaceutically acceptable salt, or solvate thereof. [0014] In some embodiments, the compound is a compound of Formula (D1-1): or a pharmaceutically acceptable salt, or solvate thereof. [0015] In some embodiments, the compound is a compound of Formula (D2-1): or a pharmaceutically acceptable salt, or solvate thereof. [0016] In one aspect, provided herein is a compound of Formula (A-2): , or a pharmaceutically acceptable salt, or solvate thereof, wherein: X is O or NM ³ ; M ¹ , M ² , and M ³ are each independently hydrogen, unsubstituted or substituted C1-C4 alkyl, unsubstituted or substituted C ₂ -C ₄ alkenyl, unsubstituted or substituted C ₂ -C ₄ alkynyl, unsubstituted or substituted C1-C4 fluoroalkyl, unsubstituted or substituted C3 cycloalkyl, or unsubstituted or substituted C1-C4 heteroalkyl; is a single bond or a double bond; Y ¹ is N or CR ¹ ; Y ² is N or CR ² ; Y ³ is N or CR ³ ; and Y ⁴ is N or CR ⁴ ; Z ⁴ is N or CR ⁸ ; R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, -CN, -OR ¹⁰ , -CO2R ¹⁰ , - C(=O)N(R ¹⁰ ) ₂ , -N(R ¹⁰ ) ₂ , -NR ¹⁰ C(=O)R ¹¹ , -SR ¹⁰ , -S(=O)R ¹¹ , -SO ₂ R ¹¹ , -SO ₂ N(R ¹⁰ ) ₂ , or - N(R ¹⁰ )SO ₂ R ¹¹ ; each R ¹⁰ is independently selected from hydrogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, and 4- to 6-membered heterocycloalkyl; or two R ¹⁰ on the same N atom are taken together with the N atom to which they are attached to form an unsubstituted or substituted N-containing 4- to 6-membered heterocycloalkyl; and each R ¹¹ is independently selected from unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, and 4- to 6-membered heterocycloalkyl; wherein each substituted alkyl, substituted alkenyl, substituted alkynyl, substituted fluoroalkyl, substituted heteroalkyl, substituted cycloalkyl, and substituted heterocycloalkyl is substituted with one or more R ^s groups independently selected from halogen, C ₁ -C ₆ alkyl, monocyclic carbocycle, monocyclic heterocycle, -CN, -OR ¹² , - CO2R ¹² , -C(=O)N(R ¹² )2, -N(R ¹² )2, -NR ¹² C(=O)R ¹³ , -SR ¹² , -S(=O)R ¹³ , -SO2R ¹³ , - SO2N(R ¹² )2, and -N(R ¹² )SO2R ¹³ ; each R ¹² is independently selected from hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₃ -C ₆ cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl and 6-membered heteroaryl; or two R ¹² groups are taken together with the N atom to which they are attached to form a N-containing 4- to 6-membered heterocycloalkyl; each R ¹³ is independently selected from C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl and 6-membered heteroaryl; and wherein 0, 1, or 2 of Y ¹ , Y ² , Y ³ , and Y ⁴ are N. [0017] In some embodiments, the compound is a compound of Formula (A1-2): or a pharmaceutically acceptable salt, or solvate thereof. [0018] In some embodiments, the compound is a compound of Formula (A2-2): or a pharmaceutically acceptable salt, or solvate thereof. [0019] In some embodiments, the compound is a compound of Formula (B-2): Formula (B-2), or a pharmaceutically acceptable salt, or solvate thereof. [0020] In some embodiments, the compound is a compound of Formula (B1-2): Formula (B1-2), or a pharmaceutically acceptable salt, or solvate thereof. [0021] In some embodiments, the compound is a compound of Formula (B2-2): or a pharmaceutically acceptable salt, or solvate thereof. [0022] In some embodiments, the compound is a compound of Formula (C-2): Formula (C-2), or a pharmaceutically acceptable salt, or solvate thereof. [0023] In some embodiments, the compound is a compound of Formula (C1-2): Formula (C1-2), or a pharmaceutically acceptable salt, or solvate thereof. [0024] In some embodiments, the compound is a compound of Formula (C2-2): or a pharmaceutically acceptable salt, or solvate thereof. [0025] In some embodiments, the compound is a compound of Formula (D-2): Formula (D-2), or a pharmaceutically acceptable salt, or solvate thereof. [0026] In some embodiments, the compound is a compound of Formula (D1-2): Formula (D1-2), or a pharmaceutically acceptable salt, or solvate thereof. [0027] In some embodiments, the compound is a compound of Formula (D2-2): Formula (D2-2), or a pharmaceutically acceptable salt, or solvate thereof. [0028] In some embodiments, the compound is a compound of Formula (D1-2a) or Formula (D1-2b): Formula (D1-2a) Formula (D1-2b), or a pharmaceutically acceptable salt, or solvate thereof. [0029] In one aspect, provided herein is a compound of Formula (A-3): or a pharmaceutically acceptable salt, or solvate thereof, wherein: X is O or NM ³ ; M ¹ , M ² , and M ³ are each independently hydrogen, unsubstituted or substituted C1-C4 alkyl, unsubstituted or substituted C ₂ -C ₄ alkenyl, unsubstituted or substituted C ₂ -C ₄ alkynyl, unsubstituted or substituted C ₁ -C ₄ fluoroalkyl, unsubstituted or substituted C ₃ cycloalkyl, or unsubstituted or substituted C1-C4 heteroalkyl; is a single bond or a double bond; , Z ¹ is N or CR ⁵ ; Z ² is N or CR ⁶ ; Z ³ is N or CR ⁷ ; Z ⁴ is N or CR ⁸ ; and Z ⁵ is N or CR ⁹ ; R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, -CN, -OR ¹⁰ , -CO2R ¹⁰ , - C(=O)N(R ¹⁰ ) ₂ , -N(R ¹⁰ ) ₂ , -NR ¹⁰ C(=O)R ¹¹ , -SR ¹⁰ , -S(=O)R ¹¹ , -SO ₂ R ¹¹ , -SO ₂ N(R ¹⁰ ) ₂ , or - N(R ¹⁰ )SO ₂ R ¹¹ ; each R ¹⁰ is independently selected from hydrogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, and 4- to 6-membered heterocycloalkyl; or two R ¹⁰ on the same N atom are taken together with the N atom to which they are attached to form an unsubstituted or substituted N-containing 4- to 6-membered heterocycloalkyl; and each R ¹¹ is independently selected from unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, and 4- to 6-membered heterocycloalkyl; wherein each substituted alkyl, substituted alkenyl, substituted alkynyl, substituted fluoroalkyl, substituted heteroalkyl, substituted cycloalkyl, and substituted heterocycloalkyl is substituted with one or more R ^s groups independently selected from halogen, C1-C6 alkyl, monocyclic carbocycle, monocyclic heterocycle, -CN, -OR ¹² , - CO2R ¹² , -C(=O)N(R ¹² )2, -N(R ¹² )2, -NR ¹² C(=O)R ¹³ , -SR ¹² , -S(=O)R ¹³ , -SO2R ¹³ , - SO ₂ N(R ¹² ) ₂ , and -N(R ¹² )SO ₂ R ¹³ ; and each R ¹² is independently selected from hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl and 6-membered heteroaryl; or two R ¹² groups are taken together with the N atom to which they are attached to form a N-containing 4- to 6-membered heterocycloalkyl; each R ¹³ is independently selected from C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl and 6-membered heteroaryl. [0030] In some embodiments, the compound is a compound of Formula (A1-3): Formula (A1-3), or a pharmaceutically acceptable salt, or solvate thereof. [0031] In some embodiments, the compound is a compound of Formula (A2-3): Formula (A2-3), or a pharmaceutically acceptable salt, or solvate thereof. [0032] In some embodiments, the compound is a compound of Formula (B-3): or a pharmaceutically acceptable salt, or solvate thereof. [0033] In some embodiments, the compound is a compound of Formula (B1-3): or a pharmaceutically acceptable salt, or solvate thereof. [0034] In some embodiments, the compound is a compound of Formula (B2-3): or a pharmaceutically acceptable salt, or solvate thereof. [0035] In some embodiments, the compound is a compound of Formula (C-3): or a pharmaceutically acceptable salt, or solvate thereof. [0036] In some embodiments, the compound is a compound of Formula (C1-3): or a pharmaceutically acceptable salt, or solvate thereof. [0037] In some embodiments, the compound is a compound of Formula (C2-3): or a pharmaceutically acceptable salt, or solvate thereof. [0038] In some embodiments, the compound is a compound of Formula (D-3): , or a pharmaceutically acceptable salt, or solvate thereof. [0039] In some embodiments, the compound is a compound of Formula (D1-3): , or a pharmaceutically acceptable salt, or solvate thereof. [0040] In some embodiments, the compound is a compound of Formula (D2-3): or a pharmaceutically acceptable salt, or solvate thereof. [0041] In some embodiments, the compound is a compound of Formula (E1-3): or a pharmaceutically acceptable salt, or solvate thereof. [0042] In some embodiments, the compound is a compound of Formula (F1-3): , or a pharmaceutically acceptable salt, or solvate thereof. [0043] In some embodiments, the compound is a compound of Formula (B1-3a) or Formula (B1-3b): Formula (B1-3a) Formula (B1-3b), or a pharmaceutically acceptable salt, or solvate thereof. [0044] In one aspect, provided herein is a compound of Formula (A-4): or a pharmaceutically acceptable salt, or solvate thereof, wherein: X is O or NM ³ ; M ¹ , M ² , and M ³ are each independently hydrogen, unsubstituted or substituted C1-C4 alkyl, unsubstituted or substituted C ₂ -C ₄ alkenyl, unsubstituted or substituted C ₂ -C ₄ alkynyl, unsubstituted or substituted C1-C4 fluoroalkyl, unsubstituted or substituted C3 cycloalkyl, or unsubstituted or substituted C1-C4 heteroalkyl; is a single bond or a double bond; Y ¹ is N or CR ¹ ; Z ² is N or CR ⁶ ; R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, -CN, - OR ¹⁰ , -CO2R ¹⁰ , -C(=O)N(R ¹⁰ )2, -N(R ¹⁰ )2, -NR ¹⁰ C(=O)R ¹¹ , -SR ¹⁰ , -S(=O)R ¹¹ , -SO2R ¹¹ , - SO2N(R ¹⁰ )2, or -N(R ¹⁰ )SO2R ¹¹ ; each R ¹⁰ is independently selected from hydrogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, and 4- to 6-membered heterocycloalkyl; or two R ¹⁰ on the same N atom are taken together with the N atom to which they are attached to form an unsubstituted or substituted N-containing 4- to 6-membered heterocycloalkyl; and each R ¹¹ is independently selected from unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, and 4- to 6-membered heterocycloalkyl; wherein each substituted alkyl, substituted alkenyl, substituted alkynyl, substituted fluoroalkyl, substituted heteroalkyl, substituted cycloalkyl, and substituted heterocycloalkyl is substituted with one or more R ^s groups independently selected from halogen, C1-C6 alkyl, monocyclic carbocycle, monocyclic heterocycle, -CN, -OR ¹² , - CO2R ¹² , -C(=O)N(R ¹² )2, -N(R ¹² )2, -NR ¹² C(=O)R ¹³ , -SR ¹² , -S(=O)R ¹³ , -SO2R ¹³ , - SO ₂ N(R ¹² ) ₂ , and -N(R ¹² )SO ₂ R ¹³ ; each R ¹² is independently selected from hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₃ -C ₆ cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl and 6-membered heteroaryl; or two R ¹² groups are taken together with the N atom to which they are attached to form a N-containing 4- to 6-membered heterocycloalkyl; each R ¹³ is independently selected from C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl and 6-membered heteroaryl; wherein Y ¹ and Z ² are not both N. [0045] In some embodiments, the compound is a compound of Formula (A1-4): or a pharmaceutically acceptable salt, or solvate thereof. [0046] In some embodiments, the compound is a compound of Formula (A2-4): or a pharmaceutically acceptable salt, or solvate thereof. [0047] In some embodiments, the compound is a compound of Formula (B-4): Formula (B-4), or a pharmaceutically acceptable salt, or solvate thereof. [0048] In some embodiments, the compound is a compound of Formula (B1-4): Formula (B1-4), or a pharmaceutically acceptable salt, or solvate thereof. [0049] In some embodiments, the compound is a compound of Formula (B2-4): Formula (B2-4), or a pharmaceutically acceptable salt, or solvate thereof. [0050] In some embodiments, the compound is a compound of Formula (C-4): or a pharmaceutically acceptable salt, or solvate thereof. [0051] In some embodiments, the compound is a compound of Formula (C1-4): Formula (C1-4), or a pharmaceutically acceptable salt, or solvate thereof. [0052] In some embodiments, the compound is a compound of Formula (C2-4): or a pharmaceutically acceptable salt, or solvate thereof. [0053] In some embodiments, the compound is a compound of Formula (D-4): Formula (D-4), or a pharmaceutically acceptable salt, or solvate thereof. [0054] In some embodiments, the compound is a compound of Formula (D1-4): Formula (D1-4), or a pharmaceutically acceptable salt, or solvate thereof. [0055] In some embodiments, the compound is a compound of Formula (D2-4): Formula (D2-4), or a pharmaceutically acceptable salt, or solvate thereof. [0056] In some embodiments, the compound is a compound of Formula (E-4): Formula (E-4), or a pharmaceutically acceptable salt, or solvate thereof. [0057] In some embodiments, the compound is a compound of Formula (E1-4): Formula (E1-4), or a pharmaceutically acceptable salt, or solvate thereof. [0058] In some embodiments, the compound is a compound of Formula (E2-4): Formula (E2-4), or a pharmaceutically acceptable salt, or solvate thereof. [0059] In some embodiments, the compound is a compound of Formula (A1-4a) or Formula (A1-4b): Formula (A1-4a) Formula (A1-4b), or a pharmaceutically acceptable salt, or solvate thereof. [0060] In one aspect, provided herein is a compound selected from

acceptable salt, or solvate thereof. [0061] Any combination of the groups described above for the various variables is contemplated herein. Throughout the specification, groups and substituents thereof are chosen by one skilled in the field to provide stable moieties and compounds. [0062] Also described herein is a pharmaceutical composition comprising a compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, and at least one pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical composition is formulated for administration to a mammal by intravenous administration, subcutaneous administration, oral administration, inhalation, nasal administration, dermal administration, or ophthalmic administration. In some embodiments, the pharmaceutical composition is formulated for administration to a mammal by oral administration. In some embodiments, the pharmaceutical composition is in the form of a tablet, a pill, a capsule, a liquid, a suspension, a gel, a dispersion, a solution, an emulsion, an ointment, or a lotion. In some embodiments, the pharmaceutical composition is in the form of a tablet, a pill, or a capsule. [0063] Also described herein is a method of treating a disease or condition in a mammal that would benefit from the modulation of glutaminyl-peptide cyclotransferase like (QPCTL) protein activity comprising administering a compound described herein, or pharmaceutically acceptable salt, or solvate thereof, to the mammal in need thereof. In some embodiments, the disease or condition is cancer. In some embodiments, the cancer is a leukemia or lymphoma. In some embodiments, the leukemia or lymphoma is acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL). In some embodiments, the non-Hodgkin’s lymphoma is a B- cell lymphoma. In some embodiments, the B-cell lymphoma is selected from the group consisting of Burkitt lymphoma, hairy cell lymphoma (HCL), Waldenstrom macroglobulinemia, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B cell lymphoma (DLBCL), B cell chronic lymphocytic leukemia (B-CLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), and pre-B acute lymphoblastic leukemia (pre-B ALL). In some embodiments, the cancer is selected from the group consisting of: multiple myeloma (MM), ovarian cancer, gliomas, colon cancer, breast cancer, bladder cancer, gastric cancer, esophageal cancer, small cell lung cancer (SCLC), non- small cell lung cancer (NSCLC), head and neck squamous cell cancer, mesothelioma, melanoma, glioma, glioblastoma, and pancreatic neuroendocrine tumors. [0064] In any of the aforementioned aspects are further embodiments in which the effective amount of the compound described herein, or a pharmaceutically acceptable salt, or solvate thereof, is: (a) systemically administered to the mammal; and/or (b) administered orally to the mammal; and/or (c) intravenously administered to the mammal; and/or (d) administered by inhalation; and/or (e) administered by nasal administration; or and/or (f) administered by injection to the mammal; and/or (g) administered topically to the mammal; and/or (h) administered by ophthalmic administration; and/or (i) administered rectally to the mammal; and/or (j) administered non-systemically or locally to the mammal. [0065] In any of the aforementioned aspects are further embodiments comprising single administrations of the effective amount of the compound, including further embodiments in which the compound is administered once a day to the mammal or the compound is administered to the mammal multiple times over the span of one day. In some embodiments, the compound is administered on a continuous dosing schedule. In some embodiments, the compound is administered on a continuous daily dosing schedule. [0066] In any of the embodiments disclosed herein, the mammal is a human. [0067] In some embodiments, compounds provided herein are orally administered to a human. [0068] Articles of manufacture, which include packaging material, a compound described herein, or a pharmaceutically acceptable salt thereof, within the packaging material, and a label that indicates that the compound or composition, or pharmaceutically acceptable salt, tautomers, pharmaceutically acceptable N-oxide, pharmaceutically active metabolite, pharmaceutically acceptable prodrug, or pharmaceutically acceptable solvate thereof, is used for modulating glutaminyl-peptide cyclotransferase like (QPCTL) protein, or for the treatment, prevention or amelioration of one or more symptoms of a disease or condition that would benefit from modulating glutaminyl-peptide cyclotransferase like (QPCTL) protein, are provided. [0069] Other objects, features and advantages of the compounds, methods and compositions described herein will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating specific embodiments, are given by way of illustration only, since various changes and modifications within the spirit and scope of the instant disclosure will become apparent to those skilled in the art from this detailed description. DETAILED DESCRIPTION OF THE INVENTION [0070] Glutaminyl cyclase (QC, EC 2.3.2.5) (also known as glutaminyl-peptide cyclotransferase; QPCT) catalyzes the intramolecular cyclization of N-terminal glutamine residues into pyroglutamic acid (pGlu*) liberating ammonia. QPCT is primarily expressed in neuroendocrine tissues, such as the pituitary, and has been implicated in diseases and conditions such as Alzheimer's disease, Familial British dementia, Huntington's disease, Down syndrome, atherosclerosis, and rheumatoid arthritis. Iso glutaminyl cyclase (isoQC, also known as glutaminyl-peptide cyclotransferase like protein; QPCTL) is a related protein that differs in amino acid sequence, but performs much of the same catalytic activity as glutaminyl cyclase. However, in contrast to QPCT, QPCTL is expressed ubiquitously, and is especially abundant in peripheral blood lymphocytes and other blood cells. [0071] The CD47/SIRP-alpha (SIRPα) interaction is an important myeloid immune checkpoint whose clinical relevance has been shown by successful application of CD47 antibodies in cancer therapy. CD47 (Cluster of Differentiation 47); also known as integrin associated protein (IAP)) is expressed on cancer cells and the ligand SIRPα (Signal regulatory protein α) is expressed on myeloid cells like macrophages and NK cells. Engagement of SIRPα leads to inhibition of phagocytosis. Accordingly, high levels of CD47 allow cancer cells to avoid phagocytosis due to engagement of the SIRPα of macrophages. Thus, blocking CD47/SIRPα interactions turns off the “don’t eat me” signal and favors phagocytosis. QPCTL is critical for pyroglutamate formation on the N-terminus of CD47 shortly after biosynthesis, which is essential for the binding of CD47 to SIRPα. Accordingly, QPCTL is an attractive target to silence the “don’t eat me” signal provided by the CD47/SIRPα interaction. [0072] While there are antibody approaches in clinical development for anti-CD47 therapy, small molecule QPCTL modulators represent an attractive therapeutic approach for cancer immunotherapy. Antibodies are typically polar, heat sensitive, membrane impermeable, and subject to enzymatic degradation, and are, accordingly, not orally available and mmust be administered systemically though, for example, IV injection. In contrast, small molecule QPCTL modulators are easier and cheaper to produce than antibody therapies, and can be administered by a variety of routes, including oral administration. [0073] The CCL2/CCR2 axis is an important chemokine signaling axis in the recruitment of myeloid lineage cells with clinial significance in various cancer and inflammatory or autoimmune disorders. The N-terminus of monocyte chemoattractant protein 1 (MCP-1, aka CCL2) is a modified to a pyroglutamate (pGlu*) residue. QPCTL has been shown to have a major role in the the pyroglutamate formation on CCL2, as well as monocyte infiltration. Current strategies targeting CCL2 are based on antibodies. Accordingly, small, orally available inhibitors of QPCTL represents an alternative therapeutic strategy to treat CCL2-driven disorders. [0074] In some embodiments, the QPCTL modulators described herein have utility over a wide range of therapeutic applications. [0075] In some embodiments, the QPCTL modulators described herein are used in the treatment of a variety of diseases or conditions such as, but not limited to, cancer, inflammatory disorders, atherosclerosis/restenosis, and fibrosis. [0076] In some embodiments, the QPCTL modulators described herein are used in the treatment of cancer. In some embodiments, the cancer is a blood cancer, such as, but not limited to, a lymphoma or leukemia. In some embodiments, the leukemia or lymphoma is acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL). In some embodiments, the non-Hodgkin’s lymphoma is a B-cell lymphoma. In some embodiments, the B-cell lymphoma is selected from the group consisting of Burkitt lymphoma, hairy cell lymphoma (HCL), Waldenstrom macroglobulinemia, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B cell lymphoma (DLBCL), B cell chronic lymphocytic leukemia (B-CLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), and pre-B acute lymphoblastic leukemia (pre-B ALL). In some embodiments, the cancer is selected from the group consisting of: multiple myeloma (MM), ovarian cancer, gliomas, colon cancer, breast cancer, bladder cancer, gastric cancer, esophageal cancer, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), head and neck squamous cell cancer, mesothelioma, melanoma, glioma, glioblastoma, and pancreatic neuroendocrine tumors. [0077] In some embodiments, the cancer is a skin, tissue, or bone cancer, such as, but not limited to, a carcinoma, sarcoma, or melanoma. In some embodiments, the carcinoma, sarcoma, or melanoma is basal cell carcinoma, squamous cell carcinoma, renal cell carcinoma, invasive ductal carcinoma, adenocarcinoma, Merkel cell carcinoma, skin cancer, lung cancer, breast cancer, prostate cancer, colorectal cancer, soft tissue sarcoma, osteosarcoma, Ewing’s sarcoma, chrondrosarcoma, myeloma, or multiple myeloma. [0078] In some embodiments, the QPCTL modulators described herein are used in the treatment of a cancer which overexpresses CD47. In some emodiments, the cancer expresses CD47 in a diseased cell at 1.5 times, 2 times, 2.5 times, 3 times, or more of the level of a non- diseased cell of the same type. [0079] In some embodiments, the QPCTL modulators described herein are used in the treatment of cancer in a mammal. [0080] In some embodiments, the QPCTL modulators described herein are used in the treatment of diseases and conditions in which CCL2-CCR2 signaling plays a role. In some embodiments, the QPCTL modulators described herein are used in the treatment of of diseases and conditions involving the recruitment of myeloid lineage cells. In some embodiments, the disease or condition is an inflammatory disease, autoimmune disease, allergic inflammatory disease, or neurodegenerative disease, such as, but not limited to, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, psoriasis, psoriatic arthritis, atopic dermatitis, severe asthma, allergic rhinitis and rhinosinusitis, nasal polyposis, atherosclerosis, pulmonary arterial hypertension, non-alcoholic steatohepatitis, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, endometriosis, Alzheimer’s disease and related dementias, Parkinson’s disease, and Huntington’s disease. [0081] In some embodiments, the QPCTL modulators described herein are used in the treatment of a disease or condition in a mammal. Compounds [0082] Compounds described herein, for example compounds of Formula (A-1), Formula (A- 2), Formula (A-3), and Formula (A-4), including pharmaceutically acceptable salts, prodrugs, active metabolites, and pharmaceutically acceptable solvates thereof, are glutaminyl-peptide cyclotransferase like (QPCTL) protein modulators. In some embodiments, the compounds described herein, including pharmaceutically acceptable salts, prodrugs, active metabolites, and pharmaceutically acceptable solvates thereof, are glutaminyl-peptide cyclotransferase like (QPCTL) protein antagonists. In some embodiments, the compounds described herein, including pharmaceutically acceptable salts, prodrugs, active metabolites, and pharmaceutically acceptable solvates thereof, are glutaminyl-peptide cyclotransferase like (QPCTL) protein inhibitors. Compounds of Formula (A-1) [0083] In one aspect, provided herein is a compound of Formula (A-1): Formula (A-1), or a pharmaceutically acceptable salt, or solvate thereof, wherein: X is O or NM ³ ; M ¹ , M ² , and M ³ are each independently hydrogen, unsubstituted or substituted C ₁ -C ₄ alkyl, unsubstituted or substituted C2-C4 alkenyl, unsubstituted or substituted C2-C4 alkynyl, unsubstituted or substituted C1-C4 fluoroalkyl, unsubstituted or substituted C3 cycloalkyl, or unsubstituted or substituted C ₁ -C ₄ heteroalkyl; is a single bond or a double bond; Y ¹ is N or CR ¹ ; Y ² is N or CR ² ; Y ³ is N or CR ³ ; and Y ⁴ is N or CR ⁴ ; Z ¹ is N or CR ⁵ ; Z ² is N or CR ⁶ ; Z ³ is N or CR ⁷ ; Z ⁴ is N or CR ⁸ ; and Z ⁵ is N or CR ⁹ ; R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, -CN, - OR ¹⁰ , -CO2R ¹⁰ , -C(=O)N(R ¹⁰ )2, -N(R ¹⁰ )2, -NR ¹⁰ C(=O)R ¹¹ , -SR ¹⁰ , -S(=O)R ¹¹ , -SO2R ¹¹ , - SO ₂ N(R ¹⁰ ) ₂ , or -N(R ¹⁰ )SO ₂ R ¹¹ ; each R ¹⁰ is independently selected from hydrogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, and 4- to 6-membered heterocycloalkyl; or two R ¹⁰ on the same N atom are taken together with the N atom to which they are attached to form an unsubstituted or substituted N-containing 4- to 6-membered heterocycloalkyl; and each R ¹¹ is independently selected from unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, and 4- to 6-membered heterocycloalkyl; wherein each substituted alkyl, substituted alkenyl, substituted alkynyl, substituted fluoroalkyl, substituted heteroalkyl, substituted cycloalkyl, and substituted heterocycloalkyl is substituted with one or more R ^s groups independently selected from halogen, C1-C6 alkyl, monocyclic carbocycle, monocyclic heterocycle, -CN, -OR ¹² , - CO2R ¹² , -C(=O)N(R ¹² )2, -N(R ¹² )2, -NR ¹² C(=O)R ¹³ , -SR ¹² , -S(=O)R ¹³ , -SO2R ¹³ , - SO ₂ N(R ¹² ) ₂ , and -N(R ¹² )SO ₂ R ¹³ ; each R ¹² is independently selected from hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl and 6-membered heteroaryl; or two R ¹² groups are taken together with the N atom to which they are attached to form a N-containing 4- to 6-membered heterocycloalkyl; each R ¹³ is independently selected from C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl, and 6-membered heteroaryl; wherein 0, 1, or 2 of Y ¹ , Y ² , Y ³ , and Y ⁴ are N; wherein 0, 1, or 2 of Z ¹ , Z ² , Z ³ , Z ⁴ , and Z ⁵ are N; and . [0084] For any and all of the embodiments for the compound of Formula A-1, substituents are selected from among a subset of the listed alternatives. For example, in some embodiments, is a single bond. In other embodiments, is a double bond. [0085] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (A1-1): or a pharmaceutically acceptable salt, or solvate thereof. [0086] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (A2-1): Formula (A2-1), or a pharmaceutically acceptable salt, or solvate thereof. [0087] In some embodiments for the compound of Formula A-1, 0 or 1 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N. In some embodiments, 0 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N. In some embodiments, 1 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N. [0088] In some embodiments for the compound of Formula A-1, Y ¹ is N or CR ¹ . In some embodiments, Y ² is N or CR ² . In some embodiments, Y ³ is N or CR ³ . In some embodiments, Y ⁴ is N or CR ⁴ . In some embodiments, Y ¹ is N. In some embodiments, Y ¹ is CR ¹ . In some embodiments, Y ² is N. In some embodiments, Y ² is CR ² . In some embodiments, Y ³ is N. In some embodiments, Y ³ is CR ³ . In some embodiments, Y ⁴ is N. In some embodiments, Y ⁴ is CR ⁴ . [0089] In some embodiments for the compound of Formula A-1, Y ¹ is CR ¹ ; Y ² is CR ² ; Y ³ is CR ³ ; and Y ⁴ is CR ⁴ . In some embodiments, Y ¹ is N; Y ² is CR ² ; Y ³ is CR ³ ; and Y ⁴ is CR ⁴ . In some embodiments, Y ¹ is CR ¹ ; Y ² is N; Y ³ is CR ³ ; and Y ⁴ is CR ⁴ . In some embodiments, Y ¹ is CR ¹ ; Y ² is CR ² ; Y ³ is N; and Y ⁴ is CR ⁴ . In some embodiments, Y ¹ is CR ¹ ; Y ² is CR ² ; Y ³ is CR ³ ; and Y ⁴ is N. [0090] In some embodiments for the compound of Formula A-1, 0 or 1 of Z ¹ , Z ² , Z ³ , Z ⁴ , and Z ⁵ is N. In some embodiments, 0 of Z ¹ , Z ² , Z ³ , Z ⁴ , and Z ⁵ is N. In some embodiments, 1 of Z ¹ , Z ² , Z ³ , Z ⁴ , and Z ⁵ is N. [0091] In some embodiments for the compound of Formula A-1, Z ¹ is N or CR ⁵ . In some embodiments, Z ² is N or CR ⁶ . In some embodiments, Z ³ is N or CR ⁷ . In some embodiments, Z ⁴ is N or CR ⁸ . In some embodiments, Z ⁵ is N or CR ⁹ . In some embodiments, Z ² is N. In some embodiments, Z ² is CR ⁶ . [0092] In some embodiments for the compound of Formula A-1, Z ¹ is CR ⁵ ; Z ² is CR ⁶ ; Z ³ is CR ⁷ ; Z ⁴ is CR ⁸ ; and Z ⁵ is CR ⁹ . In some embodiments, Z ¹ is N; Z ² is CR ⁶ ; Z ³ is CR ⁷ ; Z ⁴ is CR ⁸ ; and Z ⁵ is CR ⁹ . In some embodiments, Z ¹ is CR ⁵ ; Z ² is N; Z ³ is CR ⁷ ; Z ⁴ is CR ⁸ ; and Z ⁵ is CR ⁹ . In some embodiments, Z ¹ is CR ⁵ ; Z ² is CR ⁶ ; Z ³ is N; Z ⁴ is CR ⁸ ; and Z ⁵ is CR ⁹ . In some embodiments, Z ¹ is CR ⁵ ; Z ² is CR ⁶ ; Z ³ is CR ⁷ ; Z ⁴ is N; and Z ⁵ is CR ⁹ . In some embodiments, Z ¹ is CR ⁵ ; Z ² is CR ⁶ ; Z ³ is CR ⁷ ; Z ⁴ is CR ⁸ ; and Z ⁵ is N. [0093] In some embodiments for the compound of Formula A-1, 0 or 1 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N; and 0 or 1 of Z ¹ , Z ² , Z ³ , Z ⁴ , and Z ⁵ is N. In some embodiments, 0 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N; and 0 of Z ¹ , Z ² , Z ³ , Z ⁴ , and Z ⁵ is N. In some embodiments, 0 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N; and 1 of Z ¹ , Z ² , Z ³ , Z ⁴ , and Z ⁵ is N. In some embodiments, 1 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N; and 0 of Z ¹ , Z ² , Z ³ , Z ⁴ , and Z ⁵ is N. In some embodiments, 1 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N; and 1 of Z ¹ , Z ² , Z ³ , Z ⁴ , and Z ⁵ is N. In some embodiments, 1 of Y ¹ and Y ³ is N; and 1 of Z ² and Z ⁴ is N. In some embodiments, Y ¹ is N; and 1 of Z ² and Z ⁴ is N. In some embodiments, 1 of Y ¹ and Y ³ is N; and Z ² is N. [0094] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (B-1): Formula (B-1), or a pharmaceutically acceptable salt, or solvate thereof. [0095] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (B1-1): Formula (B1-1), or a pharmaceutically acceptable salt, or solvate thereof. [0096] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (B2-1): or a pharmaceutically acceptable salt, or solvate thereof. [0097] In some embodiments for the compound of Formula A-1, Y ¹ is N; and Z ² is N or CR ⁶ . In some embodiments, Y ¹ is N; and Z ² is CR ⁶ . In some embodiments, Y ¹ is N; and Z ² is N. In some embodiments, Y ¹ is CR ¹ ; and Z ² is N or CR ⁶ . In some embodiments, Y ¹ is CR ¹ ; and Z ² is CR ⁶ . In some embodiments, Y ¹ is CR ¹ ; and Z ² is N. [0098] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (C-1): or a pharmaceutically acceptable salt, or solvate thereof. [0099] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (C1-1): or a pharmaceutically acceptable salt, or solvate thereof. [00100] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (C2-1): or a pharmaceutically acceptable salt, or solvate thereof. [00101] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (D-1): or a pharmaceutically acceptable salt, or solvate thereof. [00102] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (D1-1): or a pharmaceutically acceptable salt, or solvate thereof. [00103] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (D2-1): or a pharmaceutically acceptable salt, or solvate thereof. [00104] In some embodiments for the compound of Formula . some embodiments, X is O. In some embodiments, X is NM ³ . In some embodiments, some embodiments, M ¹ , M ² , and M ³ are each independently hydrogen, unsubstituted or substituted C1-C4 alkyl, unsubstituted or substituted C ₂ -C ₄ alkenyl, unsubstituted or substituted C ₂ -C ₄ alkynyl, unsubstituted or substituted C1-C4 fluoroalkyl, unsubstituted or substituted C3 cycloalkyl, or unsubstituted or substituted C1-C4 heteroalkyl. In some embodiments, M ¹ , M ² , and M ³ are each independently hydrogen, C ₁ -C ₃ alkyl, C ₃ cycloalkyl, or C ₁ -C ₃ fluoroalkyl. In some embodiments, M is embodiments, . some embodiments, . embodiments, . some embodiments, . embodiments, . some embodiments, . [00105] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (C1-1a), Formula (C1-1b), Formula (C1-1c), Formula (C1-1d), Formula (C1-1e), or Formula (C1-1f): Formula (C1-1a), Formula (C1-1b), Formula (C1-1c), Formula (C1-1d), Formula (C1-1e), Formula (C1-1f), or a pharmaceutically acceptable salt, or solvate thereof. [00106] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (C1-1a), Formula (C1-1d), Formula (C1-1e), or Formula (C1-1f), or a pharmaceutically acceptable salt, or solvate thereof. [00107] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (C1-1a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (C1-1b), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (C1-1c), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (C1-1d), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (C1-1e), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (C1-1f), or a pharmaceutically acceptable salt, or solvate thereof. [00108] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (C2-1a), Formula (C2-1b), Formula (C2-1c), Formula (C2-1d), Formula (C2-1e), or Formula (C2-1f): Formula (C2-1a), Formula (C2-1b), Formula (C2-1c), Formula (C2-1d), Formula (C2-1e), Formula (C2-1f), or a pharmaceutically acceptable salt, or solvate thereof. [00109] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (C2-1a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (C2-1b), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (C2-1c), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (C2-1d), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (C2-1e), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (C2-1f), or a pharmaceutically acceptable salt, or solvate thereof. [00110] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (E-1): Formula (E-1), or a pharmaceutically acceptable salt, or solvate thereof. [00111] In some embodiments for the compound of Formula A-1, the compound is a compound of Formula (E-1) or a pharmaceutically acceptable salt, or solvate thereof. [00112] In some embodiments for the compound of Formula A-1, R ¹ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ¹ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ¹ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ¹ is hydrogen, halogen, or unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ¹ is hydrogen or halogen. In some embodiments, R ¹ is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ¹ is halogen. In some embodiments, R ¹ is hydrogen. [00113] In some embodiments for the compound of Formula A-1, R ¹ is hydrogen, halogen, - CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ¹ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ¹ is hydrogen, -CN, methyl, ethyl, isopropyl, or tert-butyl. In some embodiments, R ¹ is hydrogen, -CN, or methyl. In some embodiments, R ¹ is hydrogen or -CN. In some embodiments, R ¹ is hydrogen. In some embodiments, R ¹ is -CN. [00114] In some embodiments for the compound of Formula A-1, R ² is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ² is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ² is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ² is hydrogen, halogen, or unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ² is hydrogen or halogen. In some embodiments, R ² is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ² is halogen. In some embodiments, R ² is hydrogen. [00115] In some embodiments for the compound of Formula A-1, R ³ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ³ is hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ³ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ³ is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ³ is hydrogen or halogen. In some embodiments, R ³ is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ³ is halogen. In some embodiments, R ³ is hydrogen. [00116] In some embodiments for the compound of Formula A-1, R ⁴ is hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁴ is hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ⁴ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁴ is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁴ is hydrogen or halogen. In some embodiments, R ⁴ is unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁴ is halogen. In some embodiments, R ⁴ is hydrogen. [00117] In some embodiments for the compound of Formula A-1, R ⁵ is hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁵ is hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ⁵ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁵ is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁵ is hydrogen or halogen. In some embodiments, R ⁵ is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁵ is halogen. In some embodiments, R ⁵ is hydrogen. [00118] In some embodiments for the compound of Formula A-1, R ⁶ is hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁶ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ⁶ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁶ is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁶ is hydrogen or halogen. In some embodiments, R ⁵ is unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁶ is halogen. In some embodiments, R ⁶ is hydrogen. [00119] In some embodiments for the compound of Formula A-1, R ⁷ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁷ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ⁷ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁷ is hydrogen, halogen, or unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁷ is hydrogen or halogen. In some embodiments, R ⁷ is unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁷ is halogen. In some embodiments, R ⁷ is hydrogen. [00120] In some embodiments for the compound of Formula A-1, R ⁸ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁸ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ⁸ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁸ is hydrogen, halogen, or unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁸ is hydrogen or halogen. In some embodiments, R ⁸ is unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁸ is halogen. In some embodiments, R ⁸ is hydrogen. [00121] In some embodiments for the compound of Formula A-1, R ⁹ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁹ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ⁹ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁹ is hydrogen, halogen, or unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁹ is hydrogen or halogen. In some embodiments, R ⁹ is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁹ is halogen. In some embodiments, R ⁹ is hydrogen. [00122] In some embodiments for the compound of Formula A-1, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. [00123] In some embodiments for the compound of Formula A-1, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen or halogen. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen or halogen. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen. In some embodiments, R ¹ , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁸ , and R ⁹ are each independently hydrogen and R ² and R ⁷ are hydrogen, halogen, - CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. [00124] In some embodiments for the compound of Formula A-1, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, -F, -Cl, -CN, -OCH3, -OCH2CH3, -OCH2CH2OCH3, - NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -CH ₃ , -CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , -C(CH ₃ ) ₃ , -CHF ₂ , or -CF ₃ . [00125] In some embodiments for the compound of Formula A-1, R ² , R ³ , R ⁴ , R ⁵ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, or C1-C6 alkyl. In some embodiments, R ² , R ³ , R ⁴ , R ⁵ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, or C1-C4 alkyl. In some embodiments, R ² , R ³ , R ⁴ , R ⁵ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, -F, -Cl, -CH ₃ , -CH ₂ CH ₃ , - CH(CH3)2, or -C(CH3)3. In some embodiments, R ² , R ³ , R ⁴ , R ⁵ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, -F, or -CH3. [00126] In some embodiments for the compound of Formula A-1, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, -CN, -OR ¹⁰ , -N(R ¹⁰ ) ₂ , C ₁ -C ₆ alkyl, or C ₁ -C ₆ fluoroalkyl. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ OCH ₃ , -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -CH ₃ , -CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , -C(CH ₃ ) ₃ , -CHF ₂ , or -CF ₃ . [00127] In some embodiments for the compound of Formula A-1, R ³ , R ⁴ , R ⁵ , R ⁸ , and R ⁹ are each independently hydrogen or halogen. In some embodiments, R ³ , R ⁴ , R ⁵ , R ⁸ , and R ⁹ are each hydrogen. In some embodiments, R ³ , R ⁴ , R ⁵ , R ⁸ , and R ⁹ are each hydrogen; and R ² and R ⁷ are each independently hydrogen, halogen, -CN, -OR ¹⁰ , -N(R ¹⁰ ) ₂ , C ₁ -C ₆ alkyl, or C ₁ -C ₆ fluoroalkyl. [00128] In some embodiments for the compound of Formula A-1, R ² is hydrogen, halogen, - CN, -OR ¹⁰ , -N(R ¹⁰ ) ₂ , C ₁ -C ₆ alkyl, or C ₁ -C ₆ fluoroalkyl. In some embodiments, R ² is hydrogen, halogen, or C ₁ -C ₆ alkyl. In some embodiments, R ² is hydrogen, halogen, or C ₁ -C ₄ alkyl. In some embodiments, R ² is hydrogen, -F, -Cl, -CH3, -CH2CH3, -CH(CH3)2, or -C(CH3)3. In some embodiments, R ² is hydrogen, -F, or -CH3. In some emboidments, R ² is hydrogen. In some embodiments, R ² is -F. [00129] In some embodiments for the compound of Formula A-1, R ⁷ is hydrogen, halogen, - CN, -OR ¹⁰ , -N(R ¹⁰ )2, C1-C6 alkyl, or C1-C6 fluoroalkyl. In some embodiments, R ⁷ is hydrogen, halogen, -CN, -OR ¹⁰ , or -N(R ¹⁰ )2. In some embodiments, R ⁷ is hydrogen, -F, -Cl, -CN, -OCH3, - OCH ₂ CH ₃ , -OCH ₂ CH ₂ OCH ₃ , -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -CH ₃ , -CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , -C(CH ₃ ) ₃ , -CHF ₂ , or -CF ₃ . In some embodiments, R ⁷ is hydrogen, -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , - OCH2CH2OCH3, -NH2, -NHCH3, or -N(CH3)2. In some embodiments, R ⁷ is hydrogen, -F, -Cl, - CN, -OCH3, -OCH2CH2OCH3, or -NH2. In some embodiments, R ⁷ is hydrogen or halogen. In some embodiments, R ⁷ is hydrogen, -F, or -Cl. [00130] In some embodiments for the compound of Formula A-1, R ⁷ is halogen, -CN, -OR ¹⁰ , - N(R ¹⁰ )2, C1-C6 alkyl, or C1-C6 fluoroalkyl. In some embodiments, R ⁷ is halogen, -CN, -OR ¹⁰ , or -N(R ¹⁰ ) ₂ . In some embodiments, R ⁷ is -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ OCH ₃ , - NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -CH ₃ , -CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , -C(CH ₃ ) ₃ , -CHF ₂ , or -CF ₃ . In some embodiments, R ⁷ is -F, -Cl, -CN, -OCH3, -OCH2CH3, -OCH2CH2OCH3, -NH2, -NHCH3, or - N(CH ₃ ) ₂ . In some embodiments, R ⁷ is -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₂ OCH ₃ , or -NH ₂ . In some embodiments, R ⁷ is halogen. In some embodiments, R ⁷ is -F or -Cl. In some embodiments, R ⁷ is -F. In some embodiments, R ⁷ is -Cl. [00131] In some embodiments for the compound of Formula A-1, R ² is hydrogen, -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ OCH ₃ , -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -CH ₃ , -CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , - C(CH3)3, -CHF2, or -CF3; and R ⁷ is hydrogen, -F, -Cl, -CN, -OCH3, -OCH2CH3, - OCH2CH2OCH3, -NH2, -NHCH3, -N(CH3)2, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CHF2, or - CF ₃ . [00132] In some embodiments for the compound of Formula A-1, R ² is hydrogen, halogen, or C1-C4 alkyl; and R ⁷ is halogen, -CN, -OR ¹⁰ , or -N(R ¹⁰ )2. In some embodiments, R ² is hydrogen, -F, -Cl, -CH ₃ , -CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , or -C(CH ₃ ) ₃ ; and R ⁷ is -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , - OCH ₂ CH ₂ OCH ₃ , -NH ₂ , -NHCH ₃ , or -N(CH ₃ ) ₂ . In some embodiments, R ² is hydrogen, -F, or - CH3; R ⁷ is hydrogen, -F, -Cl, -CN, -OCH3, -OCH2CH2OCH3, or -NH2. [00133] In some embodiments, the compound of Formula A-1 is selected from the compounds in Table 1, below. Table 1

Compounds of Formula (A-2) [00134] In one aspect, provided herein is a compound of Formula (A-2): or a pharmaceutically acceptable salt, or solvate thereof, wherein: X is O or NM ³ ; M ¹ , M ² , and M ³ are each independently hydrogen, unsubstituted or substituted C1-C4 alkyl, unsubstituted or substituted C ₂ -C ₄ alkenyl, unsubstituted or substituted C ₂ -C ₄ alkynyl, unsubstituted or substituted C ₁ -C ₄ fluoroalkyl, unsubstituted or substituted C ₃ cycloalkyl, or unsubstituted or substituted C1-C4 heteroalkyl; is a single bond or a double bond; Y ¹ is N or CR ¹ ; Y ² is N or CR ² ; Y ³ is N or CR ³ ; and Y ⁴ is N or CR ⁴ ; Z ⁴ is N or CR ⁸ ; R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, -CN, -OR ¹⁰ , -CO ₂ R ¹⁰ , - C(=O)N(R ¹⁰ )2, -N(R ¹⁰ )2, -NR ¹⁰ C(=O)R ¹¹ , -SR ¹⁰ , -S(=O)R ¹¹ , -SO2R ¹¹ , -SO2N(R ¹⁰ )2, or - N(R ¹⁰ )SO2R ¹¹ ; each R ¹⁰ is independently selected from hydrogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, and 4- to 6-membered heterocycloalkyl; or two R ¹⁰ on the same N atom are taken together with the N atom to which they are attached to form an unsubstituted or substituted N-containing 4- to 6-membered heterocycloalkyl; and each R ¹¹ is independently selected from unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, and 4- to 6-membered heterocycloalkyl; wherein each substituted alkyl, substituted alkenyl, substituted alkynyl, substituted fluoroalkyl, substituted heteroalkyl, substituted cycloalkyl, and substituted heterocycloalkyl is substituted with one or more R ^s groups independently selected from halogen, C ₁ -C ₆ alkyl, monocyclic carbocycle, monocyclic heterocycle, -CN, -OR ¹² , - CO2R ¹² , -C(=O)N(R ¹² )2, -N(R ¹² )2, -NR ¹² C(=O)R ¹³ , -SR ¹² , -S(=O)R ¹³ , -SO2R ¹³ , - SO ₂ N(R ¹² ) ₂ , and -N(R ¹² )SO ₂ R ¹³ ; each R ¹² is independently selected from hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₃ -C ₆ cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl and 6-membered heteroaryl; or two R ¹² groups are taken together with the N atom to which they are attached to form a N-containing 4- to 6-membered heterocycloalkyl; each R ¹³ is independently selected from C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl and 6-membered heteroaryl; and wherein 0, 1, or 2 of Y ¹ , Y ² , Y ³ , and Y ⁴ are N. [00135] For any and all of the embodiments for the compound of Formula A-2, substituents are selected from among a subset of the listed alternatives. For example, in some embodiments, is a single bond. In other embodiments, is a double bond. [00136] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (A1-2): Formula (A1-2), or a pharmaceutically acceptable salt, or solvate thereof. [00137] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (A2-2): Formula (A2-2), or a pharmaceutically acceptable salt, or solvate thereof. [00138] In some embodiments for the compound of Formula A-2, 0, 1 or 2 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N. In some embodiments, 0 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N. In some embodiments, 1 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N. In some embodiments, 2 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N. In some embodiments, Y ¹ and Y ² are N. In some embodiments, Y ¹ and Y ³ are N. In some embodiments, Y ² and Y ³ are N. In some embodiments, Y ² and Y ⁴ are N. In some embodiments, Y ³ and Y ⁴ are N. In some embodiments, Y ¹ and Y ⁴ are N. [00139] In some embodiments for the compound of Formula A-2, Y ¹ is N or CR ¹ . In some embodiments, Y ² is N or CR ² . In some embodiments, Y ³ is N or CR ³ . In some embodiments, Y ⁴ is N or CR ⁴ . In some embodiments, Y ¹ is N. In some embodiments, Y ¹ is CR ¹ . In some embodiments, Y ² is N. In some embodiments, Y ² is CR ² . In some embodiments, Y ³ is N. In some embodiments, Y ³ is CR ³ . In some embodiments, Y ⁴ is N. In some embodiments, Y ⁴ is CR ⁴ . [00140] In some embodiments for the compound of Formula A-2, Y ¹ is CR ¹ ; Y ² is CR ² ; Y ³ is CR ³ ; and Y ⁴ is CR ⁴ . In some embodiments, Y ¹ is N; Y ² is CR ² ; Y ³ is CR ³ ; and Y ⁴ is CR ⁴ . In some embodiments, Y ¹ is CR ¹ ; Y ² is N; Y ³ is CR ³ ; and Y ⁴ is CR ⁴ . In some embodiments, Y ¹ is CR ¹ ; Y ² is CR ² ; Y ³ is N; and Y ⁴ is CR ⁴ . In some embodiments, Y ¹ is CR ¹ ; Y ² is CR ² ; Y ³ is CR ³ ; and Y ⁴ is N. In some embodiments, Y ¹ is N; Y ² is N; Y ³ is CR ³ ; and Y ⁴ is CR ⁴ . In some embodiments, Y ¹ is N; Y ² is CR ² ; Y ³ is N; and Y ⁴ is CR ⁴ . In some embodiments, Y ¹ is CR ¹ ; Y ² is N; Y ³ is N; and Y ⁴ is CR ⁴ . In some embodiments, Y ¹ is CR ¹ ; Y ² is N; Y ³ is CR ³ ; and Y ⁴ is N. In some embodiments, Y ¹ is CR ¹ ; Y ² is CR ² ; Y ³ is N; and Y ⁴ is N. In some embodiments, Y ¹ is N; Y ² is CR ² ; Y ³ is CR ³ ; and Y ⁴ is N. [00141] In some embodiments for the compound of Formula A-2, 0, 1, or 2 of Z ¹ , Z ² , Z ³ , and Z ⁴ is N or NR ¹⁰ . In some embodiments, 0 of Z ¹ , Z ² , Z ³ , and Z ⁴ is N or NR ¹⁰ . In some

. In some embodiments, 2 of Z ¹ , Z ² , Z ³ , and Z ⁴ is N or NR ¹⁰ . In some embodiments,

In some embodiments, . [00142] In some embodiments for the compound of Formula A-2, 0 or 1 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N; and 0 or 1 of Z ¹ , Z ² , Z ³ , and Z ⁴ is N or NR ¹⁰ . In some embodiments, 0 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N; and 0 of Z ¹ , Z ² , Z ³ , and Z ⁴ is N or NR ¹⁰ . In some embodiments, 0 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N; and 1 of Z ¹ , Z ² , Z ³ , and Z ⁴ is N or NR ¹⁰ . In some embodiments, 1 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N; and 0 of Z ¹ , Z ² , Z ³ , and Z ⁴ is N or NR ¹⁰ . In some embodiments, 1 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N; and 1 of Z ¹ , Z ² , Z ³ , and Z ⁴ is N or NR ¹⁰ . In some In some embodiments, 0 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N; and 2 of Z ¹ , Z ² , Z ³ , and Z ⁴ is N or NR ¹⁰ . In some embodiments, 1 of Y ¹ , Y ² , Y ³ , and Y ⁴ is N; and 2 of Z ¹ , Z ² , Z ³ , and Z ⁴ is N or NR ¹⁰ . In some embodiments, embodiments, Y ¹ is N and

[00143] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (B-2): Formula (B-2), or a pharmaceutically acceptable salt, or solvate thereof. [00144] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (B1-2): Formula (B1-2), or a pharmaceutically acceptable salt, or solvate thereof. [00145] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (B2-2): Formula (B2-2), or a pharmaceutically acceptable salt, or solvate thereof. [00146] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (C-2): Formula (C-2), or a pharmaceutically acceptable salt, or solvate thereof. [00147] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (C1-2): Formula (C1-2), or a pharmaceutically acceptable salt, or solvate thereof. [00148] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (C1-3): Formula (C1-3), or a pharmaceutically acceptable salt, or solvate thereof. [00149] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (C2-2): Formula (C2-2), or a pharmaceutically acceptable salt, or solvate thereof. [00150] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (C2-3): Formula (C2-3), or a pharmaceutically acceptable salt, or solvate thereof. [00151] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (D-2): Formula (D-2), or a pharmaceutically acceptable salt, or solvate thereof. [00152] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (D1-2): Formula (D1-2), or a pharmaceutically acceptable salt, or solvate thereof. [00153] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (D2-2): Formula (D2-2), or a pharmaceutically acceptable salt, or solvate thereof. [00154] In some embodiments for the compound of Formula , O. In some embodiments, X is NM ³ . In some embodiments, . some embodiments, M ¹ , M ² , and M ³ are each independently hydrogen, unsubstituted or substituted C1-C4 alkyl, unsubstituted or substituted C2-C4 alkenyl, unsubstituted or substituted C2-C4 alkynyl, unsubstituted or substituted C1-C4 fluoroalkyl, unsubstituted or substituted C ₃ cycloalkyl, or unsubstituted or substituted C ₁ -C ₄ heteroalkyl. In some embodiments, M ¹ , M ² , and M ³ are each independently hydrogen, C1-C3 alkyl, C3 cycloalkyl, or C ₁ -C ₃ fluoroalkyl. In some embodiments, . , . some embodiments, M is . , . [00155] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (D1-2a) or Formula (D1-2b): Formula (D1-2a), Formula (D1-2b), or a pharmaceutically acceptable salt, or solvate thereof. [00156] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (D1-3a), ormula (D1-3a), or a pharmaceutically acceptable salt, or solvate thereof. [00157] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (D1-2a) or Formula (D1-2b), or a pharmaceutically acceptable salt, or solvate thereof. [00158] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (D1-2a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (D1-2b), or a pharmaceutically acceptable salt, or solvate thereof. [00159] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (D1-3a), or a pharmaceutically acceptable salt, or solvate thereof. [00160] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (D2-2a) or Formula (D2-2b): Formula (D2-2a), Formula (D2-2b), or a pharmaceutically acceptable salt, or solvate thereof. [00161] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (D2-2a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (D2-2b), or a pharmaceutically acceptable salt, or solvate thereof. [00162] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (E-2a), Formula (E-2b), or Formula (E-2c): Formula (E-2a), Formula (E-2b), Formula (E-2c), or a pharmaceutically acceptable salt, or solvate thereof. [00163] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (E-2d): Formula (E-2d), or a pharmaceutically acceptable salt, or solvate thereof. [00164] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (E-2a) or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (E-2b) or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (E-2c) or a pharmaceutically acceptable salt, or solvate thereof. [00165] In some embodiments for the compound of Formula A-2, the compound is a compound of Formula (E-2d), or a pharmaceutically acceptable salt, or solvate thereof. [00166] In some embodiments for the compound of Formula A-2, R ¹ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ¹ is hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ¹ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ¹ is hydrogen, halogen, -CN, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ¹ is hydrogen or halogen. In some embodiments, R ¹ is unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ¹ is -CN. In some embodiments, R ¹ is halogen. In some embodiments, R ¹ is hydrogen. [00167] In some embodiments for the compound of Formula A-2, R ¹ is hydrogen, halogen, - CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ¹ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ¹ is hydrogen, -CN, methyl, ethyl, isopropyl, or tert-butyl. In some embodiments, R ¹ is hydrogen, -CN, or methyl. In some embodiments, R ¹ is hydrogen or -CN. In some embodiments, R ¹ is hydrogen. In some embodiments, R ¹ is -CN. [00168] In some embodiments for the compound of Formula A-2, R ² is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ² is hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ² is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ² is hydrogen, -CN, halogen, or unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ² is hydrogen or halogen. In some embodiments, R ² is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ² is -CN. In some embodiments, R ² is halogen. In some embodiments, R ² is hydrogen. [00169] In some embodiments for the compound of Formula A-2, R ³ is hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ³ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ³ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ³ is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ³ is hydrogen or halogen. In some embodiments, R ³ is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ³ is halogen. In some embodiments, R ³ is hydrogen. [00170] In some embodiments for the compound of Formula A-2, R ⁴ is hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁴ is hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ⁴ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁴ is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁴ is hydrogen or halogen. In some embodiments, R ⁴ is unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁴ is halogen. In some embodiments, R ⁴ is hydrogen. [00171] In some embodiments for the compound of Formula A-2, R ⁵ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁵ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ⁵ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁵ is hydrogen, halogen, or unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁵ is hydrogen or halogen. In some embodiments, R ⁵ is C1-C6 alkyl. In some embodiments, R ⁵ is halogen. In some embodiments, R ⁵ is methyl. In some embodiments, R ⁵ is hydrogen. [00172] In some embodiments for the compound of Formula A-2, R ⁶ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁶ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ⁶ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, difluoropropyl, or trifluoromethyl. In some embodiments, R ⁶ is hydrogen, halogen, unsubstituted or substituted C1-C6 fluoroalkyl, or unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁶ is hydrogen or halogen. In some embodiments, R ⁶ is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁶ is C ₁ -C ₃ fluoroalkyl In some embodiments, R ⁶ is halogen. In some embodiments, R ⁶ is hydrogen. [00173] In some embodiments for the compound of Formula A-2, R ⁷ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁷ is hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ⁷ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁷ is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁷ is hydrogen or halogen. In some embodiments, R ⁷ is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁷ is halogen. In some embodiments, R ⁷ is hydrogen. [00174] In some embodiments for the compound of Formula A-2, R ⁸ is hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁸ is hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ⁸ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁸ is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁸ is hydrogen or halogen. In some embodiments, R ⁸ is unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁸ is halogen. In some embodiments, R ⁸ is methyl. In some embodiments, R ⁸ is hydrogen. [00175] In some embodiments for the compound of Formula A-2, R ¹⁰ is hydrogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, or unsubstituted or substituted 4- to 6-membered heterocycloalkyl. In some embodiments, R ¹⁰ is hydrogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 heteroalkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ¹⁰ is hydrogen, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxyethyl, N-methylamine ethyl, difluoromethyl, 1-1 difluoroethyl, 1-1 difluoropropyl or trifluoromethyl. In some embodiments, R ¹⁰ is hydrogen, unsubstituted or substituted C1-C6 alkyl or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ¹⁰ is hydrogen. In some embodiments, R ¹⁰ is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ¹⁰ is propyl. [00176] In some embodiments for the compound of Formula A-2, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, halogen, -CN, methyl, ethyl, propyl, isopropyl, tert- butyl, difluoromethyl, 1,1-difluoropropyl, or trifluoromethyl. [00177] In some embodiments for the compound of Formula A-2, R ¹ , R ³ , R ⁴ , R ⁵ , R ⁶ , and R ⁸ are each independently hydrogen or halogen. In some embodiments, R ¹ , R ³ , R ⁴ , R ⁵ , R ⁶ , and R ⁸ are each independently halogen. In some embodiments, R ¹ , R ³ , R ⁴ , R ⁵ , R ⁶ , , and R ⁸ are each independently hydrogen. In some embodiments, R ¹ , R ³ , R ⁴ , R ⁵ , R ⁶ , and R ⁸ are each independently hydrogen and R ² and R ⁷ are hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. [00178] In some embodiments for the compound of Formula A-2, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ OCH ₃ , -NH ₂ , - NHCH3, -N(CH3)2, -CH3, -CH2CH3, - CH2CH2CH3, -CH(CH3)2, -C(CH3)3, -CHF2, CH2CHF2, - CH ₂ CH ₂ CHF ₂ , or -CF ₃ . [00179] In some embodiments for the compound of Formula A-2, R ² , R ³ , R ⁴ , R ⁵ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, C1-C6 alkyl, or C1-C6 fluoroalkyl. In some embodiments, R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, halogen, C1-C4 alkyl, or C ₁ -C ₄ fluoroalkyl. In some embodiments, R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, -F, -Cl, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, CH2CHF2, - CH2CH2CHF2, or -CF3. In some embodiments, R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, -F, -CH ₃ , -CH ₂ CH ₂ CHF ₂ , or -CF ₃ . [00180] In some embodiments for the compound of Formula A-2, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, halogen, -CN, -OR ¹⁰ , -N(R ¹⁰ )2, C1-C6 alkyl, or C1-C6 fluoroalkyl. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ OCH ₃ , -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -CH ₃ , -CH2CH3, -CH(CH3)2, -C(CH3)3, -CHF2, -CH2CHF2, -CH2CH2CHF2, or -CF3. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, -F, -CN, - CH ₃ , -CH ₂ CH ₂ CH ₃ , -CH ₂ CH ₂ CHF ₂ , or -CF ₃ . In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, -F, -CH ₃ , -CH ₂ CH ₂ CH ₃ , -CH ₂ CH ₂ CHF ₂ , or -CF ₃ . In some embodiments, R ² is hydrogen, -F, or -CH3; R ³ is hydrogen; R ⁴ is hydrogen; R ⁵ is hydrogen or -CH ₃ ; R ⁶ is hydrogen, -CH ₂ CH ₂ CHF ₂ , or -CF ₃ ; and R ⁸ is hydrogen or -CH ₃ . In some embodiments, R ¹ is hydrogen or -CN; R ² is hydrogen, -F, or -CH ₃ ; R ³ is hydrogen; R ⁴ is hydrogen; R ⁵ is hydrogen or -CH3; R ⁶ is hydrogen, -CH2CH2CHF2, or -CF3; and R ⁸ is hydrogen or -CH3. In some embodiments, R ¹ is hydrogen or -CN; R ² is hydrogen, -F, or -CH3; R ⁵ is hydrogen or -CH ₃ ; R ⁶ is hydrogen, -CH ₂ CH ₂ CHF ₂ , or -CF ₃ ; R ⁸ is hydrogen or -CH ₃ ; and R ¹⁰ is hydrogen or -CH2CH2CH3. [00181] In some embodiments, the compound of Formula A-2 are selected from the compounds in Table 2, below. Table 2

Compounds of Formula (A-3) [00182] In one aspect, provided herein is a compound of Formula (A-3): or a pharmaceutically acceptable salt, or solvate thereof, wherein: X is O or NM ³ ; M ¹ , M ² , and M ³ are each independently hydrogen, unsubstituted or substituted C1-C4 alkyl, unsubstituted or substituted C2-C4 alkenyl, unsubstituted or substituted C2-C4 alkynyl, unsubstituted or substituted C ₁ -C ₄ fluoroalkyl, unsubstituted or substituted C ₃ cycloalkyl, or unsubstituted or substituted C ₁ -C ₄ heteroalkyl; is a single bond or a double bond; , Z ¹ is N or CR ⁵ ; Z ² is N or CR ⁶ ; Z ³ is N or CR ⁷ ; Z ⁴ is N or CR ⁸ ; and Z ⁵ is N or CR ⁹ ; R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ are each independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, -CN, -OR ¹⁰ , -CO2R ¹⁰ , - C(=O)N(R ¹⁰ )2, -N(R ¹⁰ )2, -NR ¹⁰ C(=O)R ¹¹ , -SR ¹⁰ , -S(=O)R ¹¹ , -SO2R ¹¹ , -SO2N(R ¹⁰ )2, or - N(R ¹⁰ )SO ₂ R ¹¹ ; each R ¹⁰ is independently selected from hydrogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, and 4- to 6-membered heterocycloalkyl; or two R ¹⁰ on the same N atom are taken together with the N atom to which they are attached to form an unsubstituted or substituted N-containing 4- to 6-membered heterocycloalkyl; and each R ¹¹ is independently selected from unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, and 4- to 6-membered heterocycloalkyl; wherein each substituted alkyl, substituted alkenyl, substituted alkynyl, substituted fluoroalkyl, substituted heteroalkyl, substituted cycloalkyl, and substituted heterocycloalkyl is substituted with one or more R ^s groups independently selected from halogen, C ₁ -C ₆ alkyl, monocyclic carbocycle, monocyclic heterocycle, -CN, -OR ¹² , - CO2R ¹² , -C(=O)N(R ¹² )2, -N(R ¹² )2, -NR ¹² C(=O)R ¹³ , -SR ¹² , -S(=O)R ¹³ , -SO2R ¹³ , - SO ₂ N(R ¹² ) ₂ , and -N(R ¹² )SO ₂ R ¹³ ; and each R ¹² is independently selected from hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₃ -C ₆ cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl and 6-membered heteroaryl; or two R ¹² groups are taken together with the N atom to which they are attached to form a N-containing 4- to 6-membered heterocycloalkyl; each R ¹³ is independently selected from C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl and 6-membered heteroaryl [00183] For any and all of the embodiments for the compound of Formula A-3, substituents are selected from among a subset of the listed alternatives. For example, in some embodiments, is a single bond. In other embodiments, is a double bond. [00184] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (A1-3): Formula (A1-3), or a pharmaceutically acceptable salt, or solvate thereof. [00185] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (A2-3): or a pharmaceutically acceptable salt, or solvate thereof. [00186] In some embodiments for the compound of Formula A-3, 0, 1, or 2 of Y ¹ , Y ² , and Y ³ is N or NR ¹⁰ . In some embodiments, 0 of Y ¹ , Y ² , and Y ³ is N or NR ¹⁰ . In some embodiments, some embodiments, 1 of Y ¹ , Y ² , and Y ³ is N or NR ¹⁰ . In ,

embodiments, 2 of Y ¹ , Y ² , and Y ³ is N or NR ¹⁰ . In some

[00187] In some embodiments for the compound of Formula A-3, 0, 1, or 2 of Z ¹ , Z ² , Z ³ , Z ⁴ , and Z ⁵ is N. In some embodiments, 0 of Z ¹ , Z ² , Z ³ , Z ⁴ , and Z ⁵ is N. In some embodiments, 1 of Z ¹ , Z ² , Z ³ , Z ⁴ , and Z ⁵ is N. In some embodiments, 2 of Z ¹ , Z ² , Z ³ , Z ⁴ , and Z ⁵ is N. [00188] In some embodiments for the compound of Formula A-3, Z ¹ is N or CR ⁵ . In some embodiments, Z ² is N or CR ⁶ . In some embodiments, Z ³ is N or CR ⁷ . In some embodiments, Z ⁴ is N or CR ⁸ . In some embodiments, Z ⁵ is N or CR ⁹ . In some embodiments, Z ² is N. In some embodiments, Z ² is CR ⁶ . [00189] In some embodiments for the compound of Formula A-3, Z ¹ is CR ⁵ ; Z ² is CR ⁶ ; Z ³ is CR ⁷ ; Z ⁴ is CR ⁸ ; and Z ⁵ is CR ⁹ . In some embodiments, Z ¹ is N; Z ² is CR ⁶ ; Z ³ is CR ⁷ ; Z ⁴ is CR ⁸ ; and Z ⁵ is CR ⁹ . In some embodiments, Z ¹ is CR ⁵ ; Z ² is N; Z ³ is CR ⁷ ; Z ⁴ is CR ⁸ ; and Z ⁵ is CR ⁹ . In some embodiments, Z ¹ is CR ⁵ ; Z ² is CR ⁶ ; Z ³ is N; Z ⁴ is CR ⁸ ; and Z ⁵ is CR ⁹ . In some embodiments, Z ¹ is CR ⁵ ; Z ² is CR ⁶ ; Z ³ is CR ⁷ ; Z ⁴ is N; and Z ⁵ is CR ⁹ . In some embodiments, Z ¹ is CR ⁵ ; Z ² is CR ⁶ ; Z ³ is CR ⁷ ; Z ⁴ is CR ⁸ ; and Z ⁵ is N. In some embodiments, Z ¹ is CR ⁵ ; Z ² is N; Z ³ is CR ⁷ ; Z ⁴ is N; and Z ⁵ is CR ⁹ . [00190] In some embodiments for the compound of Formula Z ⁴ is CR ⁸ ; and Z ⁵ is CR ⁹ . In some embodiments, and Z ¹ is CR ⁵ ; Z ² is N; Z ³ is CR ⁷ ; Z ⁴ is CR ⁸ ; and Z ⁵ is CR ⁹ . In some embodiments, [00191] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (B-3): , or a pharmaceutically acceptable salt, or solvate thereof. [00192] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (B1-3): or a pharmaceutically acceptable salt, or solvate thereof. [00193] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (B2-3): or a pharmaceutically acceptable salt, or solvate thereof. [00194] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (C-3): or a pharmaceutically acceptable salt, or solvate thereof. [00195] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (C1-3): or a pharmaceutically acceptable salt, or solvate thereof. [00196] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (C2-3): or a pharmaceutically acceptable salt, or solvate thereof. [00197] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (D-3): or a pharmaceutically acceptable salt, or solvate thereof. [00198] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (D1-3): or a pharmaceutically acceptable salt, or solvate thereof. [00199] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (D2-3): or a pharmaceutically acceptable salt, or solvate thereof. [00200] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (E1-3): or a pharmaceutically acceptable salt, or solvate thereof. [00201] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (F1-3): or a pharmaceutically acceptable salt, or solvate thereof. [00202] In some embodiments for the compound of Formula , O. In some embodiments, X is NM ³ . In some embodiments, . some embodiments, M ¹ , M ² , and M ³ are each independently hydrogen, unsubstituted or substituted C1-C4 alkyl, unsubstituted or substituted C2-C4 alkenyl, unsubstituted or substituted C ₂ -C ₄ alkynyl, unsubstituted or substituted C ₁ -C ₄ fluoroalkyl, unsubstituted or substituted C ₃ cycloalkyl, or unsubstituted or substituted C ₁ -C ₄ heteroalkyl. In some embodiments, M ¹ , M ² , and M ³ are each independently hydrogen, C1-C3 alkyl, C3 cycloalkyl, or C1-C3 fluoroalkyl. In some embodiments, . , . some embodiments, M is . , . [00203] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (B1-3a) or Formula (B1-3b): Formula (B1-3a), Formula (B1-3b), or a pharmaceutically acceptable salt, or solvate thereof. [00204] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (B2-3a) or Formula (B2-3b): Formula (B2-3a), Formula (B2-3b), or a pharmaceutically acceptable salt, or solvate thereof. [00205] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (C1-3a), Formula (C1-3b), Formula (D1-3a), or Formula (D1-3b): Formula (D1-3a), Formula (D1-3b), or a pharmaceutically acceptable salt, or solvate thereof. [00206] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (C2-3a), Formula (C2-3b), Formula (D2-3a), or Formula (D2-3b):

Formula (D2-3a), Formula (D2-3b), or a pharmaceutically acceptable salt, or solvate thereof. [00207] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (B1-3a), Formula (B1-3b), Formula (C1-3a), Formula (C1-3b), Formula (D1-3a), Formula (D1-3b), Formula (B2-3a), Formula (B2-3b), Formula (C2-3a), Formula (C2-3b), Formula (D2-3a), Formula (D2-3b),or a pharmaceutically acceptable salt, or solvate thereof. [00208] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (B1-3a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (B1-3b), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (C1-3a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (C1-3b), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (D1-3a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (D1-3b), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (B2-3a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (B2-3b), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (C2-3a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (C2-3b), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (D2-3a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (D2-3b), or a pharmaceutically acceptable salt, or solvate thereof [00209] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (F1-3a), Formula (F1-3b), Formula (F1-3c), or Formula (F1-3d):

Formula (F1-3c), Formula (F1-3d), or a pharmaceutically acceptable salt, or solvate thereof. [00210] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (F1-3e): Formula (F1-3e), or a pharmaceutically acceptable salt, or solvate thereof. [00211] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (F2-3a), Formula (F2-3b), Formula (F2-3c), or Formula (F2-3d):

Formula (F2-3c), Formula (F2-3d), or a pharmaceutically acceptable salt, or solvate thereof. [00212] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (F2-3e): Formula (F2-3e), or a pharmaceutically acceptable salt, or solvate thereof. [00213] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (F1-3a), Formula (F1-3b), Formula (F1-3c), Formula (F1-3d), Formula (F2-3a), Formula (F2-3b), Formula (F2-3c), Formula (F2-3d), or a pharmaceutically acceptable salt, or solvate thereof. [00214] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (F1-3a) or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (F1-3b) or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (F1-3c) or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (F1-3d) or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (F2-3a) or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (F2-3b) or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (F2-3c) or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (F2-3d) or a pharmaceutically acceptable salt, or solvate thereof. [00215] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (F1-3e) or Formula (F2-3e), or a pharmaceutically acceptable salt, or solvate thereof. [00216] In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (F1-3e), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments for the compound of Formula A-3, the compound is a compound of Formula (F2- 3e), or a pharmaceutically acceptable salt, or solvate thereof. [00217] In some embodiments for the compound of Formula A-3, R ¹ is hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ¹ is hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ¹ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ¹ is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ¹ is hydrogen or halogen. In some embodiments, R ¹ is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ¹ is halogen. In some embodiments, R ¹ is -CH3. In some embodiments, R ¹ is hydrogen. [00218] In some embodiments for the compound of Formula A-3, R ¹ is hydrogen, halogen, - CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ¹ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ¹ is hydrogen, -CN, methyl, ethyl, isopropyl, or tert-butyl. In some embodiments, R ¹ is hydrogen, -CN, or methyl. In some embodiments, R ¹ is hydrogen or -CN. In some embodiments, R ¹ is hydrogen. In some embodiments, R ¹ is -CN. [00219] In some embodiments for the compound of Formula A-3, R ² is hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ² is hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ² is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ² is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ² is hydrogen or halogen. In some embodiments, R ² is unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ² is halogen. In some embodiments, R ² is -CH3. In some embodiments, R ² is hydrogen. [00220] In some embodiments for the compound of Formula A-3, R ³ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ³ is hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ³ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ³ is hydrogen, halogen, or unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ³ is hydrogen or halogen. In some embodiments, R ³ is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ³ is halogen. In some embodiments, R ³ is -CH ₃ . In some embodiments, R ³ is hydrogen. [00221] In some embodiments for the compound of Formula A-3, R ⁵ is hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁵ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ⁵ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁵ is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁵ is hydrogen or halogen. In some embodiments, R ⁵ is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁵ is halogen. In some embodiments, R ⁵ is -CH3. In some embodiments, R ⁵ is hydrogen. [00222] In some embodiments for the compound of Formula A-3, R ⁶ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁶ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ⁶ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁶ is hydrogen, halogen, or unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁶ is hydrogen or halogen. In some embodiments, R ⁵ is unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁶ is halogen. In some embodiments, R ⁶ is -CH ₃ . In some embodiments, R ⁶ is hydrogen. [00223] In some embodiments for the compound of Formula A-3, R ⁷ is hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁷ is hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ⁷ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁷ is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁷ is hydrogen or halogen. In some embodiments, R ⁷ is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁷ is halogen. In some embodiments, R ⁷ is -CH3. In some embodiments, R ⁷ is hydrogen. [00224] In some embodiments for the compound of Formula A-3, R ⁸ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁸ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ⁸ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁸ is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁸ is hydrogen or halogen. In some embodiments, R ⁸ is unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁸ is halogen. In some embodiments, R ⁸ is -CH3. In some embodiments, R ⁸ is hydrogen. [00225] In some embodiments for the compound of Formula A-3, R ⁹ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁹ is hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ⁹ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁹ is hydrogen, halogen, or unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁹ is hydrogen or halogen. In some embodiments, R ⁹ is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁹ is halogen. In some embodiments, R ⁹ is -CH3. In some embodiments, R ⁹ is hydrogen. [00226] In some embodiments for the compound of Formula A-3, R ¹⁰ is hydrogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, or unsubstituted or substituted 4- to 6-membered heterocycloalkyl. In some embodiments, R ¹⁰ is hydrogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ¹⁰ is hydrogen, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxyethyl, N-methylamine ethyl, difluoromethyl, 1-1 difluoroethyl, 1-1 difluoropropyl or trifluoromethyl. In some embodiments, R ¹⁰ is hydrogen, unsubstituted or substituted C ₁ -C ₆ alkyl or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ¹⁰ is hydrogen. In some embodiments, R ¹⁰ is C1-C6 alkyl. In some embodiments, R ¹⁰ is methyl. [00227] In some embodiments for the compound of Formula A-3, R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. [00228] In some embodiments for the compound of Formula A-3, R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen or halogen. In some embodiments, R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen or halogen. In some embodiments, R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen. In some embodiments, R ¹ , R ³ , R ⁵ , R ⁶ , R ⁸ , and R ⁹ are each independently hydrogen and R ² and R ⁷ are hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. [00229] In some embodiments for the compound of Formula A-3, R ¹ , R ² , R ³ , R ⁵ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ¹ , R ² , R ³ , R ⁵ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ OCH ₃ , -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -CH ₃ , -CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , -C(CH ₃ ) ₃ , -CHF ₂ , or -CF ₃ . [00230] In some embodiments for the compound of Formula A-3, R ¹ , R ² , R ³ R ⁵ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, or C ₁ -C ₆ alkyl. In some embodiments, R ¹ , R ² , R ³ , R ⁵ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, or C ₁ -C ₄ alkyl. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, -F, -Cl, -CH3, -CH2CH3, - CH(CH3)2, or -C(CH3)3. In some embodiments, R ¹ , R ² , R ³ , R ⁵ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, -F, or -CH ₃ . [00231] In some embodiments for the compound of Formula A-3, R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, -CN, -OR ¹⁰ , -N(R ¹⁰ )2, C1-C6 alkyl, or C1-C6 fluoroalkyl. In some embodiments, R ¹ , R ² , R ³ , R ⁵ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ OCH ₃ , -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -CH ₃ , -CH2CH3, -CH(CH3)2, -C(CH3)3, -CHF2, or -CF3. In some embodiments, R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, -F, -CH3, -CH2CH2CH3, -CH2CH2CHF2, or -CF3. In some embodiments, R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, -F, or -CH3. In some embodiments, each R ¹⁰ is independently selected from hydrogen, C1-C6 alkyl, C1- C6 fluoroalkyl, and C1-C6 heteroalkyl. In some embodiments, each R ¹⁰ is independently selected from hydrogen, C1-C3 alkyl, C1-C3 fluoroalkyl, and C1-C3 heteroalkyl. In some embodiments, each R ¹⁰ is independently selected from hydrogen, -CH ₃ , -CH ₂ CH ₃ , -CH ₂ CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , - C(CH ₃ ) ₃ , -CH ₂ CH ₂ OCH ₃ , -CHF ₂ , -CH ₂ CHF ₂ , -CH ₂ CH ₂ CHF ₂ , or -CF ₃ . In some embodiments, each R ¹⁰ is independently hydrogen or -CH3. [00232] In some embodiments for the compound of Formula A-3, R ¹ , R ³ , R ⁵ , R ⁶ , R ⁸ , and R ⁹ are each independently hydrogen or halogen. In some embodiments, R ¹ , R ³ , R ⁵ , R ⁶ , R ⁸ , and R ⁹ are each hydrogen. In some embodiments, R ¹ , R ³ , R ⁵ , R ⁶ , R ⁸ , and R ⁹ are each hydrogen; and R ² and R ⁷ are each independently hydrogen, halogen, -CN, -OR ¹⁰ , -N(R ¹⁰ )2, C1-C6 alkyl, or C1-C6 fluoroalkyl. [00233] In some embodiments for the compound of Formula A-3, R ² is hydrogen, halogen, - CN, -OR ¹⁰ , -N(R ¹⁰ )2, C1-C6 alkyl, or C1-C6 fluoroalkyl. In some embodiments, R ² is hydrogen, halogen, or C ₁ -C ₆ alkyl. In some embodiments, R ² is hydrogen, halogen, or C ₁ -C ₄ alkyl. In some embodiments, R ² is hydrogen, -F, -Cl, -CH ₃ , -CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , or -C(CH ₃ ) ₃ . In some embodiments, R ² is hydrogen, -F, or -CH3. In some emboidments, R ² is hydrogen. In some embodiments, R ² is -F. In some emboidments, R ² is -CH3. [00234] In some embodiments for the compound of Formula A-3, R ⁷ is hydrogen, halogen, - CN, -OR ¹⁰ , -N(R ¹⁰ )2, C1-C6 alkyl, or C1-C6 fluoroalkyl. In some embodiments, R ⁷ is hydrogen, halogen, -CN, -OR ¹⁰ , or -N(R ¹⁰ )2. In some embodiments, R ⁷ is hydrogen, -F, -Cl, -CN, -OCH3, - OCH ₂ CH ₃ , -OCH ₂ CH ₂ OCH ₃ , -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -CH ₃ , -CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , -C(CH ₃ ) ₃ , -CHF ₂ , or -CF ₃ . In some embodiments, R ⁷ is hydrogen, -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , - OCH2CH2OCH3, -NH2, -NHCH3, or -N(CH3)2. In some embodiments, R ⁷ is hydrogen, -F, -Cl, - CN, -OCH ₃ , -OCH ₂ CH ₂ OCH ₃ , or -NH ₂ . In some embodiments, R ⁷ is hydrogen or halogen. In some embodiments, R ⁷ is hydrogen, -F, or -Cl. In some embodiments, R ⁷ is -F. [00235] In some embodiments for the compound of Formula A-3, R ⁷ is halogen, -CN, -OR ¹⁰ , - N(R ¹⁰ )2, C1-C6 alkyl, or C1-C6 fluoroalkyl. In some embodiments, R ⁷ is halogen, -CN, -OR ¹⁰ , or -N(R ¹⁰ ) ₂ . In some embodiments, R ⁷ is -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ OCH ₃ , - NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -CH ₃ , -CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , -C(CH ₃ ) ₃ , -CHF ₂ , or -CF ₃ . In some embodiments, R ⁷ is -F, -Cl, -CN, -OCH3, -OCH2CH3, -OCH2CH2OCH3, -NH2, -NHCH3, or - N(CH ₃ ) ₂ . In some embodiments, R ⁷ is -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₂ OCH ₃ , or -NH ₂ . In some embodiments, R ⁷ is halogen. In some embodiments, R ⁷ is -F or -Cl. In some embodiments, R ⁷ is -F. In some embodiments, R ⁷ is -Cl. [00236] In some embodiments, the compound of Formula A-3 are selected from the compounds in Table 3, below. Table 3 Compounds of Formula (A-4) [00237] In one aspect, provided herein is a compound of Formula (A-4): or a pharmaceutically acceptable salt, or solvate thereof, wherein: X is O or NM ³ ; M ¹ , M ² , and M ³ are each independently hydrogen, unsubstituted or substituted C1-C4 alkyl, unsubstituted or substituted C ₂ -C ₄ alkenyl, unsubstituted or substituted C ₂ -C ₄ alkynyl, unsubstituted or substituted C1-C4 fluoroalkyl, unsubstituted or substituted C3 cycloalkyl, or unsubstituted or substituted C1-C4 heteroalkyl; is a single bond or a double bond; Y ¹ is N or CR ¹ ; Z ² is N or CR ⁶ ; R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, -CN, - OR ¹⁰ , -CO2R ¹⁰ , -C(=O)N(R ¹⁰ )2, -N(R ¹⁰ )2, -NR ¹⁰ C(=O)R ¹¹ , -SR ¹⁰ , -S(=O)R ¹¹ , -SO2R ¹¹ , - SO2N(R ¹⁰ )2, or -N(R ¹⁰ )SO2R ¹¹ ; each R ¹⁰ is independently selected from hydrogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, and 4- to 6-membered heterocycloalkyl; or two R ¹⁰ on the same N atom are taken together with the N atom to which they are attached to form an unsubstituted or substituted N-containing 4- to 6-membered heterocycloalkyl; and each R ¹¹ is independently selected from unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, and 4- to 6-membered heterocycloalkyl; wherein each substituted alkyl, substituted alkenyl, substituted alkynyl, substituted fluoroalkyl, substituted heteroalkyl, substituted cycloalkyl, and substituted heterocycloalkyl is substituted with one or more R ^s groups independently selected from halogen, C1-C6 alkyl, monocyclic carbocycle, monocyclic heterocycle, -CN, -OR ¹² , - CO2R ¹² , -C(=O)N(R ¹² )2, -N(R ¹² )2, -NR ¹² C(=O)R ¹³ , -SR ¹² , -S(=O)R ¹³ , -SO2R ¹³ , - SO ₂ N(R ¹² ) ₂ , and -N(R ¹² )SO ₂ R ¹³ ; each R ¹² is independently selected from hydrogen, C ₁ -C ₆ alkyl, C ₁ -C ₆ heteroalkyl, C ₃ -C ₆ cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl and 6-membered heteroaryl; or two R ¹² groups are taken together with the N atom to which they are attached to form a N-containing 4- to 6-membered heterocycloalkyl; each R ¹³ is independently selected from C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl and 6-membered heteroaryl; wherein Y ¹ and Z ² are not both N. [00238] For any and all of the embodiments for the compound of Formula A-4, substituents are selected from among a subset of the listed alternatives. For example, in some embodiments, is a single bond. In other embodiments, is a double bond. [00239] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (A1-4): Formula (A1-4), or a pharmaceutically acceptable salt, or solvate thereof. [00240] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (A2-4): or a pharmaceutically acceptable salt, or solvate thereof. [00241] In some embodiments for the compound of Formula A-4, Y ¹ is N and Z ² is CR ⁶ . In some embodiments, Y ¹ is CR ¹ and Z ² is N. In some embodiments, Y ¹ is CR ¹ and Z ² is CR ⁶ . [00242] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (B-4): Formula (B-4), or a pharmaceutically acceptable salt, or solvate thereof. [00243] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (B1-4): Formula (B1-4), or a pharmaceutically acceptable salt, or solvate thereof. [00244] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (B2-4): Formula (B2-4), or a pharmaceutically acceptable salt, or solvate thereof. [00245] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (C-4): Formula (C-4), or a pharmaceutically acceptable salt, or solvate thereof. [00246] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (C1-4): Formula (C1-4), or a pharmaceutically acceptable salt, or solvate thereof. [00247] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (C2-4): Formula (C2-4), or a pharmaceutically acceptable salt, or solvate thereof. [00248] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (D-4): Formula (D-4), or a pharmaceutically acceptable salt, or solvate thereof. [00249] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (D1-4): Formula (D1-4), or a pharmaceutically acceptable salt, or solvate thereof. [00250] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (D2-4): Formula (D2-4), or a pharmaceutically acceptable salt, or solvate thereof. [00251] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (E-4): or a pharmaceutically acceptable salt, or solvate thereof. [00252] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (E1-4): or a pharmaceutically acceptable salt, or solvate thereof. [00253] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (E2-4): or a pharmaceutically acceptable salt, or solvate thereof. [00254] In some embodiments for the compound of Formula , O. In some embodiments, X is NM ³ . In some embodiments, . some embodiments, M ¹ , M ² , and M ³ are each independently hydrogen, unsubstituted or substituted C1-C4 alkyl, unsubstituted or substituted C2-C4 alkenyl, unsubstituted or substituted C2-C4 alkynyl, unsubstituted or substituted C1-C4 fluoroalkyl, unsubstituted or substituted C ₃ cycloalkyl, or unsubstituted or substituted C ₁ -C ₄ heteroalkyl. In some embodiments, M ¹ , M ² , and M ³ are each independently hydrogen, C ₁ -C ₃ alkyl, C ₃ cycloalkyl, or C1-C3 fluoroalkyl. In some embodiments, . , . some embodiments, M is some embodiments, . some embodiments, . [00255] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (A1-4a) or Formula (A1-4b): Formula (A1-4a), Formula (A1-4b), or a pharmaceutically acceptable salt, or solvate thereof, wherein Y ¹ and Z ² are not both N. [00256] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (A2-4a) or Formula (A2-4b): Formula (A2-4a), Formula (A2-4b), or a pharmaceutically acceptable salt, or solvate thereof, wherein Y ¹ and Z ² are not both N. [00257] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (A1-4a), Formula (A1-4b), Formula (A2-4a), Formula (A2-4b), or a pharmaceutically acceptable salt, or solvate thereof. [00258] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (A1-4a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (A1-4b), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (A2-4a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (A2-4b), or a pharmaceutically acceptable salt, or solvate thereof. [00259] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (F1-4a) or Formula (F1-4b): Formula (F1-4a), Formula (F1-4b), or a pharmaceutically acceptable salt, or solvate thereof. [00260] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (F2-4a) or Formula (F2-4b): Formula (F2-4a), Formula (F2-4b), or a pharmaceutically acceptable salt, or solvate thereof. [00261] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (F1-4a), Formula (F1-4b), Formula (F2-4a), Formula (F2-4b), or a pharmaceutically acceptable salt, or solvate thereof. [00262] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (F1-4a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (F1-4b), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (F2-4a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (F2-4b), or a pharmaceutically acceptable salt, or solvate thereof. [00263] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (G1-4a) or Formula (G1-4b): Formula (G1-4a), Formula (G1-4b), or a pharmaceutically acceptable salt, or solvate thereof. [00264] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (G2-4a) or Formula (G2-4b):

Formula (G2-4a), Formula (G2-4b), or a pharmaceutically acceptable salt, or solvate thereof. [00265] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (G1-4a), Formula (G1-4b), Formula (G2-4a), Formula (G2-4b), or a pharmaceutically acceptable salt, or solvate thereof. [00266] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (G1-4a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (G1-4b), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (G2-4a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (G2-4b), or a pharmaceutically acceptable salt, or solvate thereof. [00267] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (H1-4a) or Formula (H1-4b): Formula (H1-4a), Formula (H1-4b), or a pharmaceutically acceptable salt, or solvate thereof. [00268] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (H1-4c): Formula (H1-4c), or a pharmaceutically acceptable salt, or solvate thereof. [00269] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (H2-4a) or Formula (H2-4b): Formula (H2-4a), Formula (H2-4b), or a pharmaceutically acceptable salt, or solvate thereof. [00270] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (H2-4c):

Formula (H2-4c), or a pharmaceutically acceptable salt, or solvate thereof. [00271] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (H1-4a), Formula (H1-4b), Formula (H2-4a), Formula (H2-4b), or a pharmaceutically acceptable salt, or solvate thereof. [00272] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (H1-4a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (H1-4b), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (H2-4a), or a pharmaceutically acceptable salt, or solvate thereof. In some embodiments, the compound is a compound of Formula (H2-4b), or a pharmaceutically acceptable salt, or solvate thereof. [00273] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (H1-4c) or Formula (H2-4c), or a pharmaceutically acceptable salt, or solvate thereof. [00274] In some embodiments for the compound of Formula A-4, the compound is a compound of Formula (H1-4c) or a pharmaceutically acceptable salt, or solvate thereof. the compound is a compound of Formula (H2-4c), or a pharmaceutically acceptable salt, or solvate thereof. [00275] In some embodiments for the compound of Formula A-4, R ¹ is hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ¹ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ¹ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ¹ is hydrogen, halogen, -CN, or unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ¹ is hydrogen, -CN, or C ₁ -C ₃ alkyl.In some embodiments, R ¹ is hydrogen or halogen. In some embodiments, R ¹ is methyl. In some embodiments, R ¹ is -CN. In some embodiments, R ¹ is hydrogen. [00276] In some embodiments for the compound of Formula A-4, R ¹ is hydrogen, halogen, - CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ¹ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ¹ is hydrogen, -CN, methyl, ethyl, isopropyl, or tert-butyl. In some embodiments, R ¹ is hydrogen, -CN, or methyl. In some embodiments, R ¹ is hydrogen or -CN. In some embodiments, R ¹ is hydrogen. In some embodiments, R ¹ is -CN. [00277] In some embodiments for the compound of Formula A-4, R ² is hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ² is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ² is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ² is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ² is hydrogen or halogen. In some embodiments, R ² is hydrogen or unsubstituted or substituted C1- C ₆ alkyl. In some embodiments, R ² is C ₁ -C ₃ alkyl. In some embodiments, R ² is halogen. In some embodiments, R ² is hydrogen. In some embodiments, R ² is methyl. [00278] In some embodiments for the compound of Formula A-4, R ³ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ³ is hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ³ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ³ is hydrogen, halogen, or unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ³ is hydrogen or halogen. In some embodiments, R ³ is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ³ is halogen. In some embodiments, R ³ is hydrogen. [00279] In some embodiments for the compound of Formula A-4, R ⁴ is hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁴ is hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ⁴ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁴ is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁴ is hydrogen or halogen. In some embodiments, R ⁴ is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁴ is halogen. In some embodiments, R ⁴ is hydrogen. [00280] In some embodiments for the compound of Formula A-4, R ⁵ is hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁵ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C1-C6 fluoroalkyl. In some embodiments, R ⁵ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁵ is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. R ⁵ is hydrogen, halogen, or C ₁ - C3 alkyl In some embodiments, R ⁵ is hydrogen, halogen, or methyl. In some embodiments, R ⁵ is C ₁ -C ₃ alkyl. In some embodiments, R ⁵ is halogen. In some embodiments, R ⁵ is hydrogen. [00281] In some embodiments for the compound of Formula A-4, R ⁶ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁶ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ⁶ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, methoxy difluoromethyl, or trifluoromethyl. In some embodiments, R ⁶ is hydrogen, halogen, methoxy, or unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁶ is hydrogen, halogen, or methoxy. In some embodiments, R ⁶ is methoxy. In some embodiments, R ⁶ is halogen. In some embodiments, R ⁶ is hydrogen. [00282] In some embodiments for the compound of Formula A-4, R ⁷ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁷ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 fluoroalkyl, or unsubstituted or substituted C1-C6 heteroalkyl. In some embodiments, R ⁷ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, methoxy, - OCH2CH2CH3, -OCF3, -OCH2CH2CHF2, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁷ is -F, -CN, -OCH3, -OCH2CH2CH3, -OCF3, or -OCH2CH2CHF2. In some embodiments, R ⁷ is hydrogen, halogen, or unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁷ is hydrogen or halogen. In some embodiments, R ⁷ is unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁷ is halogen. In some embodiments, R ⁷ is hydrogen. [00283] In some embodiments for the compound of Formula A-4, R ⁸ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁸ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ⁸ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁸ is hydrogen, halogen, or unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁸ is hydrogen or halogen. In some embodiments, R ⁸ is unsubstituted or substituted C ₁ -C ₆ alkyl. In some embodiments, R ⁸ is halogen. In some embodiments, R ⁸ is hydrogen. [00284] In some embodiments, R ⁸ is hydrogen, halogen, or -OR ¹⁰ . In some embodiments, R ⁸ is hydrogen, -Cl, -F, -Br, -OCH3, or -OCH2CH3. In some embodiments, R ⁸ is hydrogen. In soeme embodiments, R ⁸ is -Cl. In some embodiments, R ⁸ is -OCH ₃ . [00285] In some embodiments for the compound of Formula A-4, R ⁹ is hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ⁹ is hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ⁹ is hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. In some embodiments, R ⁹ is hydrogen, halogen, or unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁹ is hydrogen or halogen. In some embodiments, R ⁹ is unsubstituted or substituted C1-C6 alkyl. In some embodiments, R ⁹ is halogen. In some embodiments, R ⁹ is hydrogen. [00286] In some embodiments for the compound of Formula A-4, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, or unsubstituted or substituted C ₁ -C ₆ fluoroalkyl. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, -CN, methyl, ethyl, isopropyl, tert-butyl, difluoromethyl, or trifluoromethyl. [00287] In some embodiments for the compound of Formula A-4, R ¹ , R ³ , R ⁴ , R ⁸ , and R ⁹ are each independently C1-C3 alkyl, hydrogen or halogen. In some embodiments, R ¹ , R ³ , R ⁴ , R ⁸ , and R ⁹ are each independently hydrogen or halogen. In some embodiments, R ¹ , R ³ , R ⁴ , R ⁸ , and R ⁹ are each independently hydrogen. In some embodiments, R ¹ , R ³ , R ⁴ , R ⁸ , and R ⁹ are each independently hydrogen and R ² , R ⁵ , R ⁶ , R ⁷ are each independently hydrogen, halogen, -CN, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 fluoroalkyl, or unsubstituted or substituted C ₁ -C ₆ heteroalkyl. [00288] In some embodiments for the compound of Formula A-4, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C ₂ -C ₆ alkynyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, or -CN. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, -CN, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₁ -C ₆ fluoroalkyl, or or unsubstituted or substituted C ₁ -C ₆ heteroalkyl. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, -F, -Cl, - CN, -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ OCH ₃ , -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -CH ₃ , -CH ₂ CH ₃ , - CH(CH ₃ ) ₂ , -C(CH ₃ ) ₃ , -CHF ₂ , -CF ₃ , OCF ₃ , or -OCH ₂ CH ₂ CHF ₂ . [00289] In some embodiments for the compound of Formula A-4, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, -CN, -OR ¹⁰ , -N(R ¹⁰ )2, C1-C6 alkyl, or C1-C6 fluoroalkyl. In some embodiments, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, -F, -Cl, -CN, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH2CH2OCH3, -NH2, -NHCH3, -N(CH3)2, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CHF2, -CF3 ,-OCF3, or -OCH2CH2CHF2. In some embodiments, R ¹ is hydrogen, -F, -Cl, -CN, -OCH3, -OCH2CH3, -OCH2CH2OCH3, -NH2, - NHCH ₃ , -N(CH ₃ ) ₂ , -CH ₃ , -CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , -C(CH ₃ ) ₃ , -CHF ₂ , or -CF ₃ ; R ² is hydrogen, -F, - Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ OCH ₃ , -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -CH ₃ , -CH ₂ CH ₃ , - CH(CH3)2, -C(CH3)3, -CHF2, or -CF3; R ⁵ is hydrogen, -F, -Cl, -CN, -OCH3, -OCH2CH3, - OCH2CH2OCH3, -NH2, -NHCH3, -N(CH3)2, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CHF2, or - CF ₃ ; R ⁶ is hydrogen, -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ OCH ₃ , -NH ₂ , -NHCH ₃ , - N(CH3)2, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CHF2, or -CF3; and R ⁷ is hydrogen, -F, -Cl, - CN, -OCH3, -OCH2CH3, -OCH2CH2CH3, -OCH2CH2OCH3, -NH2, -NHCH3, -N(CH3)2, -CH3, - CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , -C(CH ₃ ) ₃ , -CHF ₂ , -CF ₃ ,-OCF ₃ , or -OCH ₂ CH ₂ CHF ₂ . In some embodiments, R ¹ is hydrogen, CH ₃ , or -CN; R ² is hydrogen, or -CH ₃ ; R ⁵ is hydrogen, -F, or - CH3; R ⁶ is hydrogen, -F, or -OCH3; and R ⁷ is -F, -CN, -OCH3, -OCH2CH2CH3, -OCF3, or - OCH ₂ CH ₂ CHF ₂ . In some embodiments, R ¹ is hydrogen, CH ₃ , or -CN; R ² is hydrogen, or -CH ₃ ; R ⁵ is hydrogen, -F, or -CH ₃ ; R ⁶ is hydrogen, -F, or -OCH ₃ ; and R ⁷ is -F, -CN, -OCH ₃ , - OCH2CH2CH3, -OCF3, or -OCH2CH2CHF2. [00290] In some embodiments for the compound of Formula A-4, R ³ , R ⁴ , R ⁵ , R ⁸ , and R ⁹ are each independently hydrogen or halogen. In some embodiments, R ³ , R ⁴ , R ⁵ , R ⁸ , and R ⁹ are each hydrogen. In some embodiments, R ³ , R ⁴ , R ⁵ , R ⁸ , and R ⁹ are each hydrogen; and R ¹ , R ² and R ⁷ are each independently hydrogen, halogen, -CN, -OR ¹⁰ , -N(R ¹⁰ )2, C1-C6 alkyl, or C1-C6 fluoroalkyl. [00291] In some embodiments for the compound of Formula A-4, R ² is hydrogen, halogen, - CN, -OR ¹⁰ , -N(R ¹⁰ )2, C1-C6 alkyl, or C1-C6 fluoroalkyl. In some embodiments, R ² is hydrogen, - F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ CH ₃ , -OCH ₂ CH ₂ OCH ₃ , -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , - CH ₃ , -CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , -C(CH ₃ ) ₃ , -CHF ₂ , -CF ₃ ,-OCF ₃ , or -OCH ₂ CH ₂ CHF ₂ . In some embodiments, R ² is hydrogen, -F, -Cl, -CN, -OCH3, -OCH2CH3, -OCH2CH2OCH3, -NH2, - NHCH3, -N(CH3)2, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CHF2, or -CF3. In some embodiments, R ² is hydrogen, -F, or -CH ₃ . In some emboidments, R ² is hydrogen. In some embodiments, R ² is -F. In some emboidments, R ² is -CH ₃ . [00292] In some embodiments for the compound of Formula A-4, R ⁷ is hydrogen, halogen, - CN, -OR ¹⁰ , -N(R ¹⁰ ) ₂ , C ₁ -C ₆ alkyl, or C ₁ -C ₆ fluoroalkyl. In some embodiments, R ⁷ is hydrogen, halogen, -CN, -OR ¹⁰ , or -N(R ¹⁰ ) ₂ . In some embodiments, R ⁷ is hydrogen, -F, -Cl, -CN, -OCH ₃ , - OCH2CH3, -OCH2CH2CH3, -OCH2CH2OCH3, -NH2, -NHCH3, -N(CH3)2, -CH3, -CH2CH3, - CH(CH3)2, -C(CH3)3, -CHF2, -CF3 ,-OCF3, or -OCH2CH2CHF2. In some embodiments, R ⁷ is hydrogen, -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ OCH ₃ , -NH ₂ , -NHCH ₃ , or -N(CH ₃ ) ₂ . In some embodiments, R ⁷ is hydrogen, -F, -Cl, -CN, -OCH3, -OCH2CH3, -OCH2CH2CH3, - OCH2CH2OCH3, -NH2, -NHCH3, -N(CH3)2, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CHF2, - CF3 ,-OCF3, or -OCH2CH2CHF2. In some embodiments, R ⁷ is hydrogen, -F, -CN, -OCH3, - OCH ₂ CH ₂ CH ₃ , -OCF ₃ , or -OCH ₂ CH ₂ CHF ₂ . In some embodiments, R ⁷ is hydrogen or halogen. In some embodiments, R ⁷ is hydrogen, -F, or -Cl. [00293] R ⁷ is halogen, -CN, -OR ¹⁰ , -N(R ¹⁰ )2, C1-C6 alkyl, or C1-C6 fluoroalkyl. In some embodiments, R ⁷ is hydrogen, halogen, -CN, -OR ¹⁰ , or -N(R ¹⁰ )2. In some embodiments, R ⁷ is -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ CH ₃ , -OCH ₂ CH ₂ OCH ₃ , -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , - CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CHF2, -CF3 ,-OCF3, or -OCH2CH2CHF2. In some embodiments, R ⁷ is -F, -Cl, -CN, -OCH3, -OCH2CH3, -OCH2CH2OCH3, -NH2, -NHCH3, or - N(CH ₃ ) ₂ . In some embodiments, R ⁷ is -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ CH ₃ , - OCH ₂ CH ₂ OCH ₃ , -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -CH ₃ , -CH ₂ CH ₃ , -CH(CH ₃ ) ₂ , -C(CH ₃ ) ₃ , -CHF ₂ , - CF3 ,-OCF3, or -OCH2CH2CHF2. In some embodiments, R ⁷ is -F, -CN, -OCH3, -OCH2CH2CH3, -OCF ₃ , or -OCH ₂ CH ₂ CHF ₂ . In some embodiments, R ⁷ is halogen. In some embodiments, R ⁷ is - F, or -Cl. [00294] In some embodiments for the compound of Formula A-4, R ² is hydrogen, -F, -Cl, -CN, -OCH3, -OCH2CH3, -OCH2CH2OCH3, -NH2, -NHCH3, -N(CH3)2, -CH3, -CH2CH3, -CH(CH3)2, - C(CH ₃ ) ₃ , -CHF ₂ , or -CF ₃ ; and R ⁷ is hydrogen, -F, -Cl, -CN, -OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ CH ₂ CH ₃ , -OCH2CH2OCH3, -NH2, -NHCH3, -N(CH3)2, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CHF2, - CF3 ,-OCF3, or -OCH2CH2CHF2. [00295] In some embodiments, the compound of Formula A-4 are selected from the compounds in Table 4, below. Table 4

[00296] In some embodiments, the compound is selected from the compounds in Table 5, below. Table 5 [00297] Any combination of the groups described above for the various variables is contemplated herein. Throughout the specification, groups and substituents thereof are chosen by one skilled in the field to provide stable moieties and compounds. [00298] In one aspect, compounds described herein are in the form of pharmaceutically acceptable salts. As well, active metabolites of these compounds having the same type of activity are included in the scope of the present disclosure. In addition, the compounds described herein can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. The solvated forms of the compounds presented herein are also considered to be disclosed herein. [00299] “Pharmaceutically acceptable,” as used herein, refers a material, such as a carrier or diluent, which does not abrogate the biological activity or properties of the compound, and is relatively nontoxic at the concentration or amount used, i.e., the material is administered to an individual without causing undesirable biological effects or interacting in a deleterious manner with any of the components of the composition in which it is contained. [00300] The term “pharmaceutically acceptable salt” refers to a form of a therapeutically active agent that consists of a cationic form of the therapeutically active agent in combination with a suitable anion, or in alternative embodiments, an anionic form of the therapeutically active agent in combination with a suitable cation. Handbook of Pharmaceutical Salts: Properties, Selection and Use. International Union of Pure and Applied Chemistry, Wiley-VCH 2002. S.M. Berge, L.D. Bighley, D.C. Monkhouse, J. Pharm. Sci.1977, 66, 1-19. P. H. Stahl and C. G. Wermuth, editors, Handbook of Pharmaceutical Salts: Properties, Selection and Use, Weinheim/Zürich:Wiley-VCH/VHCA, 2002. Pharmaceutical salts typically are more soluble and more rapidly soluble in stomach and intestinal juices than non-ionic species and so are useful in solid dosage forms. Furthermore, because their solubility often is a function of pH, selective dissolution in one or another part of the digestive tract is possible and this capability can be manipulated as one aspect of delayed and sustained release behaviors. Also, because the salt-forming molecule can be in equilibrium with a neutral form, passage through biological membranes can be adjusted. [00301] In some embodiments, pharmaceutically acceptable salts are obtained by reacting a compound described herein with an acid. In some embodiments, the compound described herein (i.e. free base form) is basic and is reacted with an organic acid or an inorganic acid. Inorganic acids include, but are not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, and metaphosphoric acid. Organic acids include, but are not limited to, 1-hydroxy-2-naphthoic acid; 2,2-dichloroacetic acid; 2-hydroxyethanesulfonic acid; 2- oxoglutaric acid; 4-acetamidobenzoic acid; 4-aminosalicylic acid; acetic acid; adipic acid; ascorbic acid (L); aspartic acid (L); benzenesulfonic acid; benzoic acid; camphoric acid (+); camphor-10-sulfonic acid (+); capric acid (decanoic acid); caproic acid (hexanoic acid); caprylic acid (octanoic acid); carbonic acid; cinnamic acid; citric acid; cyclamic acid; dodecylsulfuric acid; ethane-1,2-disulfonic acid; ethanesulfonic acid; formic acid; fumaric acid; galactaric acid; gentisic acid; glucoheptonic acid (D); gluconic acid (D); glucuronic acid (D); glutamic acid; glutaric acid; glycerophosphoric acid; glycolic acid; hippuric acid; isobutyric acid; lactic acid (DL); lactobionic acid; lauric acid; maleic acid; malic acid (- L); malonic acid; mandelic acid (DL); methanesulfonic acid; naphthalene-1,5-disulfonic acid; naphthalene-2-sulfonic acid; nicotinic acid; oleic acid; oxalic acid; palmitic acid; pamoic acid; phosphoric acid; proprionic acid; pyroglutamic acid (- L); salicylic acid; sebacic acid; stearic acid; succinic acid; sulfuric acid; tartaric acid (+ L); thiocyanic acid; toluenesulfonic acid (p); and undecylenic acid. [00302] In some embodiments, a compound described herein is prepared as a chloride salt, sulfate salt, bromide salt, mesylate salt, maleate salt, citrate salt or phosphate salt. [00303] In some embodiments, pharmaceutically acceptable salts are obtained by reacting a compound described herein with a base. In some embodiments, the compound described herein is acidic and is reacted with a base. In such situations, an acidic proton of the compound described herein is replaced by a metal ion, e.g., lithium, sodium, potassium, magnesium, calcium, or an aluminum ion. In some cases, compounds described herein coordinate with an organic base, such as, but not limited to, ethanolamine, diethanolamine, triethanolamine, tromethamine, meglumine, N-methylglucamine, dicyclohexylamine, tris(hydroxymethyl)methylamine. In other cases, compounds described herein form salts with amino acids such as, but not limited to, arginine, lysine, and the like. Acceptable inorganic bases used to form salts with compounds that include an acidic proton, include, but are not limited to, aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydroxide, lithium hydroxide, and the like. In some embodiments, the compounds provided herein are prepared as a sodium salt, calcium salt, potassium salt, magnesium salt, meglumine salt, N-methylglucamine salt or ammonium salt. [00304] It should be understood that a reference to a pharmaceutically acceptable salt includes the solvent addition forms. In some embodiments, solvates contain either stoichiometric or non- stoichiometric amounts of a solvent, and are formed during the process of crystallization with pharmaceutically acceptable solvents such as water, ethanol, and the like. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. Solvates of compounds described herein are conveniently prepared or formed during the processes described herein. In addition, the compounds provided herein optionally exist in unsolvated as well as solvated forms. [00305] The methods and formulations described herein include the use of N-oxides (if appropriate), or pharmaceutically acceptable salts of compounds described herein, as well as active metabolites of these compounds having the same type of activity. [00306] In some embodiments, sites on the organic radicals (e.g. alkyl groups, aromatic rings) of compounds described herein are susceptible to various metabolic reactions. Incorporation of appropriate substituents on the organic radicals will reduce, minimize or eliminate this metabolic pathway. In specific embodiments, the appropriate substituent to decrease or eliminate the susceptibility of the aromatic ring to metabolic reactions is, by way of example only, a halogen, deuterium, an alkyl group, a haloalkyl group, or a deuteroalkyl group. [00307] In another embodiment, the compounds described herein are labeled isotopically (e.g. with a radioisotope) or by another other means, including, but not limited to, the use of chromophores or fluorescent moieties, bioluminescent labels, or chemiluminescent labels. [00308] Compounds described herein include isotopically-labeled compounds, which are identical to those recited in the various formulae and structures presented herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into the present compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, sulfur, fluorine chlorine, iodine, phosphorus, such as, for example, ² H, ³ H, ¹³ C, ¹⁴ C, ¹⁵ N, ¹⁸ O, ¹⁷ O, ³⁵ S, ¹⁸ F, ³⁶ Cl, ¹²³ I, ¹²⁴ I, ¹²⁵ I, ¹³¹ I, ³² P and ³³ P. In one aspect, isotopically-labeled compounds described herein, for example those into which radioactive isotopes such as ³ H and ¹⁴ C are incorporated, are useful in drug and/or substrate tissue distribution assays. In one aspect, substitution with isotopes such as deuterium affords certain therapeutic advantages resulting from greater metabolic stability, such as, for example, increased in vivo half-life or reduced dosage requirements. [00309] In some embodiments, the compounds described herein possess one or more stereocenters and each stereocenter exists independently in either the R or S configuration. In some embodiments, the compound described herein exists in the R configuration. In some embodiments, the compound described herein exists in the S configuration. The compounds presented herein include all diastereomeric, individual enantiomers, atropisomers, and epimeric forms as well as the appropriate mixtures thereof. The compounds and methods provided herein include all cis, trans, syn, anti, entgegen (E), and zusammen (Z) isomers as well as the appropriate mixtures thereof. [00310] Individual stereoisomers are obtained, if desired, by methods such as, stereoselective synthesis and/or the separation of stereoisomers by chiral chromatographic columns or the separation of diastereomers by either non-chiral or chiral chromatographic columns or crystallization and recrystallization in a proper solvent or a mixture of solvents. In certain embodiments, compounds described herein are prepared as their individual stereoisomers by reacting a racemic mixture of the compound with an optically active resolving agent to form a pair of diastereoisomeric compounds/salts, separating the diastereomers and recovering the optically pure individual enantiomers. In some embodiments, resolution of individual enantiomers is carried out using covalent diastereomeric derivatives of the compounds described herein. In another embodiment, diastereomers are separated by separation/resolution techniques based upon differences in solubility. In other embodiments, separation of stereoisomers is performed by chromatography or by the forming diastereomeric salts and separation by recrystallization, or chromatography, or any combination thereof. Jean Jacques, Andre Collet, Samuel H. Wilen, “Enantiomers, Racemates and Resolutions”, John Wiley And Sons, Inc., 1981. In some embodiments, stereoisomers are obtained by stereoselective synthesis. [00311] In some embodiments, compounds described herein are prepared as prodrugs. A “prodrug” refers to an agent that is converted into the parent drug in vivo. Prodrugs are often useful because, in some situations, they are easier to administer than the parent drug. They are, for instance, bioavailable by oral administration whereas the parent is not. Further or alternatively, the prodrug also has improved solubility in pharmaceutical compositions over the parent drug. In some embodiments, the design of a prodrug increases the effective water solubility. An example, without limitation, of a prodrug is a compound described herein, which is administered as an ester (the “prodrug”) but then is metabolically hydrolyzed to provide the active entity. A further example of a prodrug is a short peptide (polyaminoacid) bonded to an acid group where the peptide is metabolized to reveal the active moiety. In certain embodiments, upon in vivo administration, a prodrug is chemically converted to the biologically, pharmaceutically or therapeutically active form of the compound. In certain embodiments, a prodrug is enzymatically metabolized by one or more steps or processes to the biologically, pharmaceutically or therapeutically active form of the compound. [00312] Prodrugs of the compounds described herein include, but are not limited to, esters, ethers, carbonates, thiocarbonates, N-acyl derivatives, N-acyloxyalkyl derivatives, N- alkyloxyacyl derivatives, quaternary derivatives of tertiary amines, N-Mannich bases, Schiff bases, amino acid conjugates, phosphate esters, and sulfonate esters. See for example Design of Prodrugs, Bundgaard, A. Ed., Elseview, 1985 and Method in Enzymology, Widder, K. et al., Ed.; Academic, 1985, vol.42, p.309-396; Bundgaard, H. “Design and Application of Prodrugs” in A Textbook of Drug Design and Development, Krosgaard-Larsen and H. Bundgaard, Ed., 1991, Chapter 5, p.113-191; and Bundgaard, H., Advanced Drug Delivery Review, 1992, 8, 1- 38, each of which is incorporated herein by reference. In some embodiments, a hydroxyl group in the compounds disclosed herein is used to form a prodrug, wherein the hydroxyl group is incorporated into an acyloxyalkyl ester, alkoxycarbonyloxyalkyl ester, alkyl ester, aryl ester, phosphate ester, sugar ester, ether, and the like. In some embodiments, a hydroxyl group in the compounds disclosed herein is a prodrug wherein the hydroxyl is then metabolized in vivo to provide a carboxylic acid group. In some embodiments, a carboxyl group is used to provide an ester or amide (i.e. the prodrug), which is then metabolized in vivo to provide a carboxylic acid group. In some embodiments, compounds described herein are prepared as alkyl ester prodrugs. [00313] Prodrug forms of the herein described compounds, wherein the prodrug is metabolized in vivo to produce a compound described herein are included within the scope of the claims. In some cases, some of the herein-described compounds is a prodrug for another derivative or active compound. [00314] In some embodiments, any one of the hydroxyl group(s), amino group(s) and/or carboxylic acid group(s) are functionalized in a suitable manner to provide a prodrug moiety. In some embodiments, the prodrug moiety is as described above. [00315] In additional or further embodiments, the compounds described herein are metabolized upon administration to an organism in need to produce a metabolite that is then used to produce a desired effect, including a desired therapeutic effect. [00316] A “metabolite” of a compound disclosed herein is a derivative of that compound that is formed when the compound is metabolized. The term “active metabolite” refers to a biologically active derivative of a compound that is formed when the compound is metabolized. The term “metabolized,” as used herein, refers to the sum of the processes (including, but not limited to, hydrolysis reactions and reactions catalyzed by enzymes) by which a particular substance is changed by an organism. Thus, enzymes may produce specific structural alterations to a compound. For example, cytochrome P450 catalyzes a variety of oxidative and reductive reactions while uridine diphosphate glucuronyltransferases catalyze the transfer of an activated glucuronic-acid molecule to aromatic alcohols, aliphatic alcohols, carboxylic acids, amines and free sulfhydryl groups. Metabolites of the compounds disclosed herein are optionally identified either by administration of compounds to a host and analysis of tissue samples from the host, or by incubation of compounds with hepatic cells in vitro and analysis of the resulting compounds. [00317] In some instances, heterocyclic rings may exist in tautomeric forms. In such situations, it is understood that the structures of said compounds are illustrated or named in one tautomeric form but could be illustrated or named in the alternative tautomeric form. The alternative tautomeric forms are expressly included in this disclosure, such as, for example, the structures illustrated below. For example, benzimidazoles or imidazoles could exist in the following tautomeric forms: Synthesis of Compounds [00318] Compounds described herein are synthesized using standard synthetic techniques or using methods known in the art in combination with methods described herein. [00319] Unless otherwise indicated, conventional methods of mass spectroscopy, NMR, HPLC are employed. [00320] Compounds are prepared using standard organic chemistry techniques such as those described in, for example, March’s Advanced Organic Chemistry, 6 ^th Edition, John Wiley and Sons, Inc. Alternative reaction conditions for the synthetic transformations described herein may be employed such as variation of solvent, reaction temperature, reaction time, as well as different chemical reagents and other reaction conditions. [00321] In some embodiments, compounds described herein are prepared as described in shown below in Schemes A-D. Scheme A: X ¹ and X ² are suitable leaving groups; PG is a suitable protecting group. [00322] Protection of the acid I affords intermediate II, which is subsequently converted to intermediate III by a substitution reaction such as nucleophilic aromatic substitution (SNAr). Removal of the protecting group using appropriate de-protection methods yields intermediate IV. Intermediate IV is converted to intermediate V by an organometallic coupling reaction such as Suzuki–Miyaura reaction with a boronic acid or its ester or an organotrifluoroborate (Ar- BF3K). Acid V is treated with suitable cyclization conditions to provide the compound of Formula (A-1). The reaction steps can proceed in different orders. For example, intermediate III or IV can be treated with suitable cyclization conditions to yield intermediate VI, which is subsequently converted to the compound of Formula (A-1) by an organometallic coupling reaction such as Suzuki–Miyaura reaction with a boronic acid or its ester or an organotrifluoroborate (Ar-BF ₃ K). Compounds of Formula (A-4) can also be made according to Scheme A.

Scheme B: X ¹ and X ² are suitable leaving groups; PG is a suitable protecting group. [00323] Protection of the acid I affords intermediate II, which is subsequently converted to intermediate III by a substitution reaction such as nucleophilic aromatic substitution (SNAr). Removal of the protecting group using appropriate de-protection methods yields intermediate IV. Intermediate IV is converted to intermediate VII by an organometallic coupling reaction such as Suzuki–Miyaura reaction with a boronic acid or its ester or an organotrifluoroborate (Ar- BF ₃ K). Acid VII is treated with suitable cyclization conditions to provide the compound of Formula (A-2). The reaction steps can proceed in different orders. For example, intermediate III or IV can be treated with suitable cyclization conditions to yield intermediate VI, which is subsequently converted to the compound of Formula (A-2) by an organometallic coupling reaction such as Suzuki–Miyaura reaction with a boronic acid or its ester or an organotrifluoroborate (Ar-BF3K).

Scheme C: X ¹ and X ² are suitable leaving groups; PG is a suitable protecting group. [00324] Protection of the acid I affords intermediate II, which is subsequently converted to intermediate VIII by a substitution reaction such as nucleophilic aromatic substitution (SNAr). Removal of the protecting group using appropriate de-protection methods yields intermediate IX. Intermediate IX is converted to intermediate X by an organometallic coupling reaction such as Suzuki–Miyaura reaction with a boronic acid or its ester or an organotrifluoroborate (Ar- BF3K). Acid V is treated with suitable cyclization conditions to provide the compound of Formula (A-3). The reaction steps can proceed in different orders. For example, intermediate III or IV can be treated with suitable cyclization conditions to yield intermediate XI, which is subsequently converted to the compound of Formula (A-3) by an organometallic coupling reaction such as Suzuki–Miyaura reaction with a boronic acid or its ester or an organotrifluoroborate (Ar-BF3K). [00325] In some other embodiments, when M is a 1,2,3-trazole, compounds described herein are prepared as described in Scheme D. Scheme D: X ¹ and X ³ are suitable leaving groups; PG is a suitable protecting group. [00326] The alcohol functional group of intermediate XII is converted to a suitable leaving group, such as a halide or sulfonate leavind group, resulting in intermediate XIII. Nucelophilic azide substitution results in intermediate XIV, which is subsequently reacted with dimethyl (2- oxopropyl)phosphonate to yield intermediate XV. Removal of the protecting group using appropriate de-protection methods yields intermediate XVI. Intermediate XVI is converted to intermediate XVII by a substitution reaction such as a nucleophilic aromatic substitution (SNAr), which is subsequently converted to the compound of Formula (A-5) by an organometallic coupling reaction such as Suzuki–Miyaura reaction with a boronic acid or its ester or an organotrifluoroborate (Ar-BF3K). Certain Terminology [00327] Unless otherwise stated, the following terms used in this application have the definitions given below. The use of the term “including” as well as other forms, such as “include”, “includes,” and “included,” is not limiting. The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. [00328] As used herein, C1-Cx includes C1-C2, C1-C3... C1-Cx. By way of example only, a group designated as "C1-C6" indicates that there are one to six carbon atoms in the moiety, i.e. groups containing 1 carbon atom, 2 carbon atoms, 3 carbon atoms or 4 carbon atoms. Thus, by way of example only, "C ₁ -C ₄ alkyl" indicates that there are one to four carbon atoms in the alkyl group, i.e., the alkyl group is selected from among methyl, ethyl, propyl, iso-propyl, n-butyl, iso- butyl, sec-butyl, and t-butyl. [00329] An “alkyl” group refers to an aliphatic hydrocarbon group. The alkyl group is branched or straight chain. In some embodiments, the “alkyl” group has 1 to 10 carbon atoms, i.e. a C ₁ - C ₁₀ alkyl. Whenever it appears herein, a numerical range such as “1 to 10” refers to each integer in the given range; e.g., “1 to 10 carbon atoms” means that the alkyl group consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 10 carbon atoms, although the present definition also covers the occurrence of the term “alkyl” where no numerical range is designated. In some embodiments, an alkyl is a C1-C6alkyl. In one aspect the alkyl is methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, or t-butyl. Typical alkyl groups include, but are in no way limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tertiary butyl, pentyl, neopentyl, or hexyl. [00330] An “alkylene” group refers to a divalent alkyl radical. Any of the above mentioned monovalent alkyl groups may be an alkylene by abstraction of a second hydrogen atom from the alkyl. In some embodiments, an alkylene is a C ₁ -C ₆ alkylene. In other embodiments, an alkylene is a C1-C4alkylene. Typical alkylene groups include, but are not limited to, -CH2-, -CH2CH2-, - CH2CH2CH2-, -CH2CH2CH2CH2-, and the like. In some embodiments, an alkylene is -CH2-. [00331] An “alkoxy” group refers to a (alkyl)O- group, where alkyl is as defined herein. [00332] The term “alkylamine” refers to the –N(alkyl)xHy group, where x is 0 and y is 2, or where x is 1 and y is 1, or where x is 2 and y is 0. [00333] An “hydroxyalkyl” refers to an alkyl in which one hydrogen atom is replaced by a hydroxyl. In some embodiments, a hydroxyalkyl is a C ₁ -C ₄ hydroxyalkyl. Typical hydroxyalkyl groups include, but are not limited to, -CH2OH, -CH2CH2OH, -CH2CH2CH2OH, - CH ₂ CH ₂ CH ₂ CH ₂ OH, and the like. [00334] An “aminoalkyl” refers to an alkyl in which one hydrogen atom is replaced by an amino. In some embodiments, aminoalkyl is a C1-C4aminoalkyl. Typical aminoalkyl groups include, but are not limited to, -CH2NH2, -CH2CH2NH2, -CH2CH2CH2NH2, - CH ₂ CH ₂ CH ₂ CH ₂ NH ₂ , and the like. [00335] The term “alkenyl” refers to a type of alkyl group in which at least one carbon-carbon double bond is present. In one embodiment, an alkenyl group has the formula –C(R)=CR2, wherein R refers to the remaining portions of the alkenyl group, which may be the same or different. In some embodiments, R is H or an alkyl. In some embodiments, an alkenyl is selected from ethenyl (i.e., vinyl), propenyl (i.e., allyl), butenyl, pentenyl, pentadienyl, and the like. Non- limiting examples of an alkenyl group include -CH=CH2, -C(CH3)=CH2, -CH=CHCH3, - C(CH ₃ )=CHCH ₃ , and –CH ₂ CH=CH ₂ . [00336] The term “alkynyl” refers to a type of alkyl group in which at least one carbon-carbon triple bond is present. In one embodiment, an alkenyl group has the formula -C≡C-R, wherein R refers to the remaining portions of the alkynyl group. In some embodiments, R is H or an alkyl. In some embodiments, an alkynyl is selected from ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like. Non-limiting examples of an alkynyl group include -C≡CH, -C≡CCH ₃ - C≡CCH2CH3, -CH2C≡CH. [00337] The term “heteroalkyl” refers to an alkyl group in which one or more skeletal atoms of the alkyl are selected from an atom other than carbon, e.g., oxygen, nitrogen (e.g. –NH-, - N(alkyl)-, sulfur, or combinations thereof. A heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl. In one aspect, a heteroalkyl is a C1-C6heteroalkyl. [00338] The term “aromatic” refers to a planar ring having a delocalized ^-electron system containing 4n+2 ^ electrons, where n is an integer. The term “aromatic” includes both carbocyclic aryl (“aryl”, e.g., phenyl) and heterocyclic aryl (or “heteroaryl” or “heteroaromatic”) groups (e.g., pyridine). The term includes monocyclic or fused-ring polycyclic (i.e., rings which share adjacent pairs of carbon atoms) groups. [00339] The term “carbocyclic” or “carbocycle” refers to a ring or ring system where the atoms forming the backbone of the ring are all carbon atoms. The term thus distinguishes carbocyclic from “heterocyclic” rings or “heterocycles” in which the ring backbone contains at least one atom which is different from carbon. In some embodiments, at least one of the two rings of a bicyclic carbocycle is aromatic. In some embodiments, both rings of a bicyclic carbocycle are aromatic. Carbocycles include aryls and cycloalkyls. [00340] As used herein, the term “aryl” refers to an aromatic ring wherein each of the atoms forming the ring is a carbon atom. In one aspect, aryl is phenyl or a naphthyl. In some embodiments, an aryl is a phenyl. In some embodiments, an aryl is a phenyl, naphthyl, indanyl, indenyl, or tetrahydronaphthyl. In some embodiments, an aryl is a C6-C10aryl. Depending on the structure, an aryl group is a monoradical or a diradical (i.e., an arylene group). [00341] The term “cycloalkyl” refers to a monocyclic or polycyclic aliphatic, non-aromatic radical, wherein each of the atoms forming the ring (i.e. skeletal atoms) is a carbon atom. In some embodiments, cycloalkyls are spirocyclic or bridged compounds. In some embodiments, cycloalkyls are optionally fused with an aromatic ring, and the point of attachment is at a carbon that is not an aromatic ring carbon atom. Cycloalkyl groups include groups having from 3 to 10 ring atoms. In some embodiments, cycloalkyl groups are selected from among cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, spiro[2.2]pentyl, norbornyl and bicycle[1.1.1]pentyl. In some embodiments, a cycloalkyl is a C ₃ - C6cycloalkyl. In some embodiments, a cycloalkyl is a C3-C4cycloalkyl. [00342] The term “halo” or, alternatively, “halogen” or “halide” means fluoro, chloro, bromo or iodo. In some embodiments, halo is fluoro, chloro, or bromo. [00343] The term “fluoroalkyl” refers to an alkyl in which one or more hydrogen atoms are replaced by a fluorine atom. In one aspect, a fluoroalkyl is a C ₁ -C ₆ fluoroalkyl. [00344] The term "heterocycle" or “heterocyclic” refers to heteroaromatic rings (also known as heteroaryls) and heterocycloalkyl rings containing one to four heteroatoms in the ring(s), where each heteroatom in the ring(s) is selected from O, S and N, wherein each heterocyclic group has from 3 to 10 atoms in its ring system, and with the proviso that any ring does not contain two adjacent O or S atoms. Non-aromatic heterocyclic groups (also known as heterocycloalkyls) include rings having 3 to 10 atoms in its ring system and aromatic heterocyclic groups include rings having 5 to 10 atoms in its ring system. The heterocyclic groups include benzo-fused ring systems. Examples of non-aromatic heterocyclic groups are pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, oxazolidinonyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, thioxanyl, piperazinyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, homopiperidinyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepinyl, 1,2,3,6-tetrahydropyridinyl, pyrrolin-2-yl, pyrrolin-3-yl, indolinyl, 2H- pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, dithianyl, dithiolanyl, dihydropyranyl, dihydrothienyl, dihydrofuranyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, 3- azabicyclo[3.1.0]hexanyl, 3-azabicyclo[4.1.0]heptanyl, 3H-indolyl, indolin-2-onyl, isoindolin-1- onyl, isoindoline-1,3-dionyl, 3,4-dihydroisoquinolin-1(2H)-onyl, 3,4-dihydroquinolin-2(1H)- onyl, isoindoline-1,3-dithionyl, benzo[d]oxazol-2(3H)-onyl, 1H-benzo[d]imidazol-2(3H)-onyl, benzo[d]thiazol-2(3H)-onyl, and quinolizinyl. Examples of aromatic heterocyclic groups are pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl, and furopyridinyl. The foregoing groups are either C-attached (or C-linked) or N-attached where such is possible. For instance, a group derived from pyrrole includes both pyrrol-1-yl (N- attached) or pyrrol-3-yl (C-attached). Further, a group derived from imidazole includes imidazol-1-yl or imidazol-3-yl (both N-attached) or imidazol-2-yl, imidazol-4-yl or imidazol-5- yl (all C-attached). The heterocyclic groups include benzo-fused ring systems. Non-aromatic heterocycles are optionally substituted with one or two oxo (=O) moieties, such as pyrrolidin-2- one. In some embodiments, at least one of the two rings of a bicyclic heterocycle is aromatic. In some embodiments, both rings of a bicyclic heterocycle are aromatic. [00345] The terms “heteroaryl” or, alternatively, “heteroaromatic” refers to an aryl group that includes one or more ring heteroatoms selected from nitrogen, oxygen and sulfur. Illustrative examples of heteroaryl groups include monocyclic heteroaryls and bicyclic heteroaryls. Monocyclic heteroaryls include pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, pyridazinyl, triazinyl, oxadiazolyl, thiadiazolyl, and furazanyl. Monocyclic heteroaryls include indolizine, indole, benzofuran, benzothiophene, indazole, benzimidazole, purine, quinolizine, quinoline, isoquinoline, cinnoline, phthalazine, quinazoline, quinoxaline, 1,8-naphthyridine, and pteridine. In some embodiments, a heteroaryl contains 0-4 N atoms in the ring. In some embodiments, a heteroaryl contains 1-4 N atoms in the ring. In some embodiments, a heteroaryl contains 0-4 N atoms, 0-1 O atoms, and 0-1 S atoms in the ring. In some embodiments, a heteroaryl contains 1-4 N atoms, 0-1 O atoms, and 0-1 S atoms in the ring. In some embodiments, heteroaryl is a C1-C9heteroaryl. In some embodiments, monocyclic heteroaryl is a C ₁ -C ₅ heteroaryl. In some embodiments, monocyclic heteroaryl is a 5-membered or 6-membered heteroaryl. In some embodiments, bicyclic heteroaryl is a C ₆ -C ₉ heteroaryl. [00346] A “heterocycloalkyl” group refers to a cycloalkyl group that includes at least one heteroatom selected from nitrogen, oxygen and sulfur. In some embodiments, a heterocycloalkyl is fused with an aryl or heteroaryl. In some embodiments, the heterocycloalkyl is oxazolidinonyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, piperidin-2-onyl, pyrrolidine-2,5-dithionyl, pyrrolidine-2,5-dionyl, pyrrolidinonyl, imidazolidinyl, imidazolidin-2- onyl, or thiazolidin-2-onyl. In one aspect, a heterocycloalkyl is a C ₂ -C ₁₀ heterocycloalkyl. In another aspect, a heterocycloalkyl is a C4-C10heterocycloalkyl. In some embodiments, a heterocycloalkyl is monocyclic or bicyclic. In some embodiments, a heterocycloalkyl is monocyclic and is a 3, 4, 5, 6, 7, or 8-membered ring. In some embodiments, a heterocycloalkyl is monocyclic and is a 3, 4, 5, or 6-membered ring. In some embodiments, a heterocycloalkyl is monocyclic and is a 3 or 4-membered ring. In some embodiments, a heterocycloalkyl contains 0-2 N atoms in the ring. In some embodiments, a heterocycloalkyl contains 0-2 N atoms, 0-2 O atoms and 0-1 S atoms in the ring. [00347] The term “bond” or “single bond” refers to a chemical bond between two atoms, or two moieties when the atoms joined by the bond are considered to be part of larger substructure. In one aspect, when a group described herein is a bond, the referenced group is absent thereby allowing a bond to be formed between the remaining identified groups. [00348] The term “moiety” refers to a specific segment or functional group of a molecule. Chemical moieties are often recognized chemical entities embedded in or appended to a molecule. [00349] The term“substituted” means that the referenced group is substituted with one or more additional group(s) individually and independently selected from halogen, -CN, -NH ₂ , - NH(alkyl), -N(alkyl) ₂ , -OH, -CO ₂ H, -CO ₂ alkyl, -C(=O)NH ₂ , -C(=O)NH(alkyl), - C(=O)N(alkyl)2, -S(=O)2NH2, -S(=O)2NH(alkyl), -S(=O)2N(alkyl)2, alkyl, cycloalkyl, fluoroalkyl, heteroalkyl, alkoxy, fluoroalkoxy, heterocycloalkyl, aryl, heteroaryl, aryloxy, alkylthio, arylthio, alkylsulfoxide, arylsulfoxide, alkylsulfone, and arylsulfone. In some other embodiments, optional substituents are independently selected from halogen, -CN, -NH2, - NH(CH3), -N(CH3)2, -OH, -CO2H, -CO2(C1-C4alkyl), -C(=O)NH2, -C(=O)NH(C1-C4alkyl), - C(=O)N(C ₁ -C ₄ alkyl) ₂ , -S(=O) ₂ NH ₂ , -S(=O) ₂ NH(C ₁ -C ₄ alkyl), -S(=O) ₂ N(C ₁ -C ₄ alkyl) ₂ , C ₁ - C ₄ alkyl, C ₃ -C ₆ cycloalkyl, C ₁ -C ₄ fluoroalkyl, C ₁ -C ₄ heteroalkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ fluoroalkoxy, -SC1-C4alkyl, -S(=O)C1-C4alkyl, and -S(=O)2C1-C4alkyl. In some embodiments, optional substituents are independently selected from halogen, -CN, -NH ₂ , -OH, -NH(CH ₃ ), -N(CH ₃ ) ₂ , - CH ₃ , -CH ₂ CH ₃ , -CHF ₂ , -CF ₃ , -OCH ₃ , -OCHF ₂ , and -OCF ₃ . In some embodiments, substituted groups are substituted with one or two of the preceding groups. In some embodiments, an optional substituent on an aliphatic carbon atom (acyclic or cyclic) includes oxo (=O). [00350] The term“optionally substituted” means that the referenced group is optionally substituted with one or more additional group(s) individually and independently selected from halogen, -CN, -NH2, -NH(alkyl), -N(alkyl)2, -OH, -CO2H, -CO2alkyl, -C(=O)NH2, - C(=O)NH(alkyl), -C(=O)N(alkyl) ₂ , -S(=O) ₂ NH ₂ , -S(=O) ₂ NH(alkyl), -S(=O) ₂ N(alkyl) ₂ , alkyl, cycloalkyl, fluoroalkyl, heteroalkyl, alkoxy, fluoroalkoxy, heterocycloalkyl, aryl, heteroaryl, aryloxy, alkylthio, arylthio, alkylsulfoxide, arylsulfoxide, alkylsulfone, and arylsulfone. In some other embodiments, optional substituents are independently selected from halogen, -CN, -NH ₂ , - NH(CH ₃ ), -N(CH ₃ ) ₂ , -OH, -CO ₂ H, -CO ₂ (C ₁ -C ₄ alkyl), -C(=O)NH ₂ , -C(=O)NH(C ₁ -C ₄ alkyl), - C(=O)N(C1-C4alkyl)2, -S(=O)2NH2, -S(=O)2NH(C1-C4alkyl), -S(=O)2N(C1-C4alkyl)2, C1- C4alkyl, C3-C6cycloalkyl, C1-C4fluoroalkyl, C1-C4heteroalkyl, C1-C4alkoxy, C1-C4fluoroalkoxy, -SC ₁ -C ₄ alkyl, -S(=O)C ₁ -C ₄ alkyl, and -S(=O) ₂ C ₁ -C ₄ alkyl. In some embodiments, optional substituents are independently selected from halogen, -CN, -NH ₂ , -OH, -NH(CH ₃ ), -N(CH ₃ ) ₂ , - CH3, -CH2CH3, -CHF2, -CF3, -OCH3, -OCHF2, and -OCF3. In some embodiments, substituted groups are substituted with one or two of the preceding groups. In some embodiments, an optional substituent on an aliphatic carbon atom (acyclic or cyclic) includes oxo (=O). [00351] In some embodiments, each substituted alkyl, substituted fluoroalkyl, substituted heteroalkyl, substituted carbocycle, and substituted heterocycle is substituted with one or more R ^s groups independently selected from the group consisting of halogen, C ₁ -C ₆ alkyl, monocyclic carbocycle, monocyclic heterocycle, -CN, -OR ²¹ , -CO2R ²¹ , -C(=O)N(R ²¹ )2, -N(R ²¹ )2, - NR ²¹ C(=O)R ²² , -SR ²¹ , -S(=O)R ²² , -SO2R ²² , or -SO2N(R ²¹ )2; each R ²¹ is independently selected from hydrogen, C1-C6alkyl, C1-C6fluoroalkyl, C1-C6heteroalkyl, C3-C6cycloalkyl, C2- C ₆ heterocycloalkyl, phenyl, benzyl, 5-membered heteroaryl and 6-membered heteroaryl; or two R ²¹ groups are taken together with the N atom to which they are attached to form a N-containing heterocycle; each R ²² is independently selected from C1-C6alkyl, C1-C6fluoroalkyl, C1- C6heteroalkyl, C3-C6cycloalkyl, C2-C6heterocycloalkyl, phenyl, benzyl, 5-membered heteroaryl and 6-membered heteroaryl. [00352] The term “acceptable” with respect to a formulation, composition or ingredient, as used herein, means having no persistent detrimental effect on the general health of the subject being treated. [00353] The term “modulate” as used herein, means to interact with a target either directly or indirectly so as to alter the activity of the target, including, by way of example only, to enhance the activity of the target, to inhibit the activity of the target, to limit the activity of the target, or to extend the activity of the target. [00354] The term “modulator” as used herein, refers to a molecule that interacts with a target either directly or indirectly. The interactions include, but are not limited to, the interactions of an agonist, partial agonist, an inverse agonist, antagonist, degrader, or combinations thereof. In some embodiments, a modulator is an antagonist. In some embodiments, a modulator is an inhibitor. [00355] The terms "administer," "administering", "administration," and the like, as used herein, refer to the methods that may be used to enable delivery of compounds or compositions to the desired site of biological action. These methods include, but are not limited to oral routes, intraduodenal routes, parenteral injection (including intravenous, subcutaneous, intraperitoneal, intramuscular, intravascular or infusion), topical and rectal administration. Those of skill in the art are familiar with administration techniques that can be employed with the compounds and methods described herein. In some embodiments, the compounds and compositions described herein are administered orally. [00356] The terms “co-administration” or the like, as used herein, are meant to encompass administration of the selected therapeutic agents to a single patient, and are intended to include treatment regimens in which the agents are administered by the same or different route of administration or at the same or different time. [00357] The terms “effective amount” or “therapeutically effective amount,” as used herein, refer to a sufficient amount of an agent or a compound being administered, which will relieve to some extent one or more of the symptoms of the disease or condition being treated. The result includes reduction and/or alleviation of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. For example, an “effective amount” for therapeutic uses is the amount of the composition comprising a compound as disclosed herein required to provide a clinically significant decrease in disease symptoms. An appropriate “effective” amount in any individual case is optionally determined using techniques, such as a dose escalation study. [00358] The terms “enhance” or “enhancing,” as used herein, means to increase or prolong either in potency or duration a desired effect. Thus, in regard to enhancing the effect of therapeutic agents, the term “enhancing” refers to the ability to increase or prolong, either in potency or duration, the effect of other therapeutic agents on a system. An “enhancing-effective amount,” as used herein, refers to an amount adequate to enhance the effect of another therapeutic agent in a desired system. [00359] The term “pharmaceutical combination” as used herein, means a product that results from the mixing or combining of more than one active ingredient and includes both fixed and non-fixed combinations of the active ingredients. The term “fixed combination” means that the active ingredients, e.g. a compound described herein, or a pharmaceutically acceptable salt thereof, and a co-agent, are both administered to a patient simultaneously in the form of a single entity or dosage. The term “non-fixed combination” means that the active ingredients, e.g. a compound described herein, or a pharmaceutically acceptable salt thereof, and a co-agent, are administered to a patient as separate entities either simultaneously, concurrently or sequentially with no specific intervening time limits, wherein such administration provides effective levels of the two compounds in the body of the patient. The latter also applies to cocktail therapy, e.g. the administration of three or more active ingredients. [00360] The terms “article of manufacture” and “kit” are used as synonyms. [00361] The term “subject” or “patient” encompasses mammals. Examples of mammals include, but are not limited to, any member of the Mammalian class: humans, non-human primates such as chimpanzees, and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, swine; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents, such as rats, mice and guinea pigs, and the like. In one aspect, the mammal is a human. [00362] The terms “treat,” “treating” or “treatment,” as used herein, include alleviating, abating or ameliorating at least one symptom of a disease or condition, preventing additional symptoms, inhibiting the disease or condition, e.g., arresting the development or progression of the disease or condition, relieving the disease or condition, causing regression of the disease or condition, relieving a secondary condition caused by the disease or condition, or stopping the symptoms of the disease or condition either prophylactically and/or therapeutically. Pharmaceutical Compositions [00363] In some embodiments, the compounds described herein, including for example a compound of Formulas A-1, A-2, A-3, A-4, A-5, or A-6, or a pharmaceutically acceptable salt thereof, are formulated into pharmaceutical compositions. Pharmaceutical compositions are formulated in a conventional manner using one or more pharmaceutically acceptable inactive ingredients that facilitate processing of the active compounds into preparations that are used pharmaceutically. Proper formulation is dependent upon the route of administration chosen. A summary of pharmaceutical compositions described herein is found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington’s Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, H.A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y., 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams & Wilkins1999), herein incorporated by reference for such disclosure. [00364] In some embodiments, the compounds described herein are administered either alone or in combination with pharmaceutically acceptable carriers, excipients or diluents, in a pharmaceutical composition. Administration of the compounds and compositions described herein can be effected by any method that enables delivery of the compounds to the site of action. These methods include, though are not limited to delivery via enteral routes (including oral, gastric or duodenal feeding tube, rectal suppository and rectal enema), parenteral routes (injection or infusion, including intraarterial, intracardiac, intradermal, intraduodenal, intramedullary, intramuscular, intraosseous, intraperitoneal, intrathecal, intravascular, intravenous, intravitreal, epidural and subcutaneous), inhalational, transdermal, transmucosal, sublingual, buccal and topical (including epicutaneous, dermal, enema, eye drops, ear drops, intranasal, vaginal) administration, although the most suitable route may depend upon for example the condition and disorder of the recipient. By way of example only, compounds described herein can be administered locally to the area in need of treatment, by for example, local infusion during surgery, topical application such as creams or ointments, injection, catheter, or implant. The administration can also be by direct injection at the site of a diseased tissue or organ. [00365] In some embodiments, pharmaceutical compositions suitable for oral administration are presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution or a suspension in an aqueous liquid or a non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. In some embodiments, the active ingredient is presented as a bolus, electuary or paste. [00366] Pharmaceutical compositions which can be used orally include tablets, push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. Tablets may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with binders, inert diluents, or lubricating, surface active or dispersing agents. Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. In some embodiments, the tablets are coated or scored and are formulated so as to provide slow or controlled release of the active ingredient therein. All formulations for oral administration should be in dosages suitable for such administration. The push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In some embodiments, stabilizers are added. Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or Dragee coatings for identification or to characterize different combinations of active compound doses. [00367] In some embodiments, pharmaceutical compositions are formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. The compositions may be presented in unit-dose or multi- dose containers, for example sealed ampoules and vials, and may be stored in powder form or in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example, saline or sterile pyrogen-free water, immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets of the kind previously described. [00368] Pharmaceutical compositions for parenteral administration include aqueous and non- aqueous (oily) sterile injection solutions of the active compounds which may contain antioxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the compounds to allow for the preparation of highly concentrated solutions. [00369] Pharmaceutical compositions may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials (for example, as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt. [00370] For buccal or sublingual administration, the compositions may take the form of tablets, lozenges, pastilles, or gels formulated in conventional manner. Such compositions may comprise the active ingredient in a flavored basis such as sucrose and acacia or tragacanth. [00371] Pharmaceutical compositions may be administered topically, that is by non-systemic administration. This includes the application of a compound of the present invention externally to the epidermis or the buccal cavity and the instillation of such a compound into the ear, eye and nose, such that the compound does not significantly enter the blood stream. In contrast, systemic administration refers to oral, intravenous, intraperitoneal and intramuscular administration. [00372] Pharmaceutical compositions suitable for topical administration include liquid or semi- liquid preparations suitable for penetration through the skin to the site of inflammation such as gels, liniments, lotions, creams, ointments or pastes, and drops suitable for administration to the eye, ear or nose. The active ingredient may comprise, for topical administration, from 0.001% to 10% w/w, for instance from 1% to 2% by weight of the formulation. [00373] Pharmaceutical compositions for administration by inhalation are conveniently delivered from an insufflator, nebulizer pressurized packs or other convenient means of delivering an aerosol spray. Pressurized packs may comprise a suitable propellant such as dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol, the dosage unit may be determined by providing a valve to deliver a metered amount. Alternatively, for administration by inhalation or insufflation, pharmaceutical preparations may take the form of a dry powder composition, for example a powder mix of the compound and a suitable powder base such as lactose or starch. The powder composition may be presented in unit dosage form, in for example, capsules, cartridges, gelatin or blister packs from which the powder may be administered with the aid of an inhalator or insufflator. [00374] It should be understood that in addition to the ingredients particularly mentioned above, the compounds and compositions described herein may include other agents conventional in the art having regard to the type of formulation in question, for example those suitable for oral administration may include flavoring agents. Methods of Dosing and Treatment Regimens [00375] In one embodiment, the compounds described herein, for example a compound of Formulas Formulas A-1, A-2, A-3, A-4, A-5, or A-6, or a pharmaceutically acceptable salt thereof, are used in the preparation of medicaments for the treatment of diseases or conditions in a mammal that would benefit from modulation of QPCTL activity. Methods for treating any of the diseases or conditions described herein in a mammal in need of such treatment, involves administration of pharmaceutical compositions that include at least one compound described herein, or a pharmaceutically acceptable salt, active metabolite, prodrug, or pharmaceutically acceptable solvate thereof, in therapeutically effective amounts to said mammal. [00376] In certain embodiments, the compositions containing the compound(s) described herein are administered for prophylactic and/or therapeutic treatments. In certain therapeutic applications, the compositions are administered to a patient already suffering from a disease or condition, in an amount sufficient to cure or at least partially arrest at least one of the symptoms of the disease or condition. Amounts effective for this use depend on the severity and course of the disease or condition, previous therapy, the patient's health status, weight, and response to the drugs, and the judgment of the treating physician. Therapeutically effective amounts are optionally determined by methods including, but not limited to, a dose escalation and/or dose ranging clinical trial. [00377] In prophylactic applications, compositions containing the compounds described herein are administered to a patient susceptible to or otherwise at risk of a particular disease, disorder or condition. Such an amount is defined to be a "prophylactically effective amount or dose." In this use, the precise amounts also depend on the patient's state of health, weight, and the like. When used in patients, effective amounts for this use will depend on the severity and course of the disease, disorder or condition, previous therapy, the patient's health status and response to the drugs, and the judgment of the treating physician. In one aspect, prophylactic treatments include administering to a mammal, who previously experienced at least one symptom of the disease being treated and is currently in remission, a pharmaceutical composition comprising a compound described herein, or a pharmaceutically acceptable salt thereof, in order to prevent a return of the symptoms of the disease or condition. [00378] In certain embodiments wherein the patient’s condition does not improve, upon the doctor’s discretion the administration of the compounds are administered chronically, that is, for an extended period of time, including throughout the duration of the patient’s life in order to ameliorate or otherwise control or limit the symptoms of the patient’s disease or condition. [00379] Once improvement of the patient's conditions has occurred, a maintenance dose is administered if necessary. Subsequently, in specific embodiments, the dosage or the frequency of administration, or both, is reduced, as a function of the symptoms, to a level at which the improved disease, disorder or condition is retained. In certain embodiments, however, the patient requires intermittent treatment on a long-term basis upon any recurrence of symptoms. [00380] The amount of a given agent that corresponds to such an amount varies depending upon factors such as the particular compound, disease condition and its severity, the identity (e.g., weight, sex) of the subject or host in need of treatment, but nevertheless is determined according to the particular circumstances surrounding the case, including, e.g., the specific agent being administered, the route of administration, the condition being treated, and the subject or host being treated. [00381] In general, however, doses employed for adult human treatment are typically in the range of 0.01 mg-2000 mg per day. In one embodiment, the desired dose is conveniently presented in a single dose or in divided doses administered simultaneously or at appropriate intervals, for example as two, three, four or more sub-doses per day. [00382] In one embodiment, the daily dosages appropriate for the compound described herein, or a pharmaceutically acceptable salt thereof, described herein are from about 0.01 to about 50 mg/kg per body weight. In some embodiments, the daily dosage or the amount of active in the dosage form are lower or higher than the ranges indicated herein, based on a number of variables in regard to an individual treatment regime. In various embodiments, the daily and unit dosages are altered depending on a number of variables including, but not limited to, the activity of the compound used, the disease or condition to be treated, the mode of administration, the requirements of the individual subject, the severity of the disease or condition being treated, and the judgment of the practitioner. [00383] Toxicity and therapeutic efficacy of such therapeutic regimens are determined by standard pharmaceutical procedures in cell cultures or experimental animals, including, but not limited to, the determination of the LD ₅₀ and the ED ₅₀ . The dose ratio between the toxic and therapeutic effects is the therapeutic index and it is expressed as the ratio between LD50 and ED50. In certain embodiments, the data obtained from cell culture assays and animal studies are used in formulating the therapeutically effective daily dosage range and/or the therapeutically effective unit dosage amount for use in mammals, including humans. In some embodiments, the daily dosage amount of the compounds described herein lies within a range of circulating concentrations that include the ED50 with minimal toxicity. In certain embodiments, the daily dosage range and/or the unit dosage amount varies within this range depending upon the dosage form employed and the route of administration utilized. [00384] In any of the aforementioned aspects are further embodiments in which the effective amount of the compound described herein, or a pharmaceutically acceptable salt thereof, is: (a) systemically administered to the mammal; and/or (b) administered orally to the mammal; and/or (c) intravenously administered to the mammal; and/or (d) administered by injection to the mammal; and/or (e) administered topically to the mammal; and/or (f) administered non- systemically or locally to the mammal. [00385] In any of the aforementioned aspects are further embodiments comprising single administrations of the effective amount of the compound, including further embodiments in which (i) the compound is administered once a day; or (ii) the compound is administered to the mammal multiple times over the span of one day. [00386] In any of the aforementioned aspects are further embodiments comprising multiple administrations of the effective amount of the compound, including further embodiments in which (i) the compound is administered continuously or intermittently: as in a single dose; (ii) the time between multiple administrations is every 6 hours; (iii) the compound is administered to the mammal every 8 hours; (iv) the compound is administered to the mammal every 12 hours; (v) the compound is administered to the mammal every 24 hours. In further or alternative embodiments, the method comprises a drug holiday, wherein the administration of the compound is temporarily suspended or the dose of the compound being administered is temporarily reduced; at the end of the drug holiday, dosing of the compound is resumed. In one embodiment, the length of the drug holiday varies from 2 days to 1 year. Combination Treatments [00387] In certain instances, it is appropriate to administer at least one compound described herein, for example a compound of Formulas A-1, A-2, A-3, A-4, A-5, or A-6, or a pharmaceutically acceptable salt thereof, in combination with one or more other therapeutic agents. [00388] In one embodiment, the therapeutic effectiveness of one of the compounds described herein is enhanced by administration of an adjuvant (i.e., by itself the adjuvant has minimal therapeutic benefit, but in combination with another therapeutic agent, the overall therapeutic benefit to the patient is enhanced). Or, in some embodiments, the benefit experienced by a patient is increased by administering one of the compounds described herein with another agent (which also includes a therapeutic regimen) that also has therapeutic benefit. [00389] In one specific embodiment, a compound described herein, or a pharmaceutically acceptable salt thereof, is co-administered with a second therapeutic agent, wherein the compound described herein, or a pharmaceutically acceptable salt thereof, and the second therapeutic agent modulate different aspects of the disease, disorder or condition being treated, thereby providing a greater overall benefit than administration of either therapeutic agent alone. [00390] In any case, regardless of the disease, disorder or condition being treated, the overall benefit experienced by the patient is simply be additive of the two therapeutic agents or the patient experiences a synergistic benefit. [00391] For combination therapies described herein, dosages of the co-administered compounds vary depending on the type of co-drug employed, on the specific drug employed, on the disease or condition being treated and so forth. In additional embodiments, when co- administered with one or more other therapeutic agents, the compound provided herein is administered either simultaneously with the one or more other therapeutic agents, or sequentially. [00392] In combination therapies, the multiple therapeutic agents (one of which is one of the compounds described herein) are administered in any order or even simultaneously. If administration is simultaneous, the multiple therapeutic agents are, by way of example only, provided in a single, unified form, or in multiple forms (e.g., as a single pill or as two separate pills). Combination Treatments with Immune Checkpoint Inhibitors [00393] In one aspect, the present disclosure provides a method for treating cancer comprising administering a compound or salt of the present disclosure to a subject in need thereof in combination with an immune checkpoint inhibitor. In some embodiments, the method comprises administering to the subject a compound of Formulas A-1, A-2, A-3, A-4, A-5, or A-6, or a pharmaceutically salt thereof, in comprination with an immune checkpoint inhibitor. In some embodiments, the method comprises administering to the subject a compound of Formulas A-1, A-2, A-3, A-4, A-5, or A-6, or a pharmaceutically salt thereof, and administering to the subject an immune checkpoint inhibitor. In some embodiments, the immune checkpoint inhibitor is a PD-L1 inhibitor. In some embodiments, the immune checkpoint inhibitor is a PD-1 inhibitor. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. [00394] In some embodiments, the compound of the present disclosure used for the methods described above is a compound of Formula (A-6): or a pharmaceutically acceptable salt, or solvate thereof, wherein: X is N or CH; R is H, NH2, or NHCH3; is a single bond or a double bond; Y ¹ is N or CR ¹ ; Y ² is N or CR ² ; Y ³ is N or CR ³ ; and Y ⁴ is N or CR ⁴ ; Z ¹ is N or CR ⁵ ; Z ² is N or CR ⁶ ; Z ³ is N or CR ⁷ ; Z ⁴ is N or CR ⁸ ; and Z ⁵ is N or CR ⁹ ; R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , and R ⁹ are each independently hydrogen, halogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₂ -C ₆ alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, unsubstituted or substituted 4- to 6-membered heterocycloalkyl, -CN, - OR ¹⁰ , -CO2R ¹⁰ , -C(=O)N(R ¹⁰ )2, -N(R ¹⁰ )2, -NR ¹⁰ C(=O)R ¹¹ , -SR ¹⁰ , -S(=O)R ¹¹ , -SO2R ¹¹ , - SO2N(R ¹⁰ )2, or -N(R ¹⁰ )SO2R ¹¹ ; each R ¹⁰ is independently selected from hydrogen, unsubstituted or substituted C ₁ -C ₆ alkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, 4- to 6-membered heterocycloalkyl; or two R ¹⁰ on the same N atom are taken together with the N atom to which they are attached to form an unsubstituted or substituted N-containing 4- to 6-membered heterocycloalkyl; and each R ¹¹ is independently selected from unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C ₁ -C ₆ heteroalkyl, unsubstituted or substituted C ₃ -C ₆ cycloalkyl, 4- to 6-membered heterocycloalkyl; wherein each substituted alkyl, substituted alkenyl, substituted alkynyl, substituted fluoroalkyl, substituted heteroalkyl, substituted cycloalkyl, and substituted heterocycloalkyl is substituted with one or more R ^s groups independently selected from the group consisting of halogen, C1-C6 alkyl, monocyclic carbocycle, monocyclic heterocycle, -CN, -OR ¹² , -CO2R ¹² , -C(=O)N(R ¹² )2, -N(R ¹² )2, -NR ¹² C(=O)R ¹³ , -SR ¹² , - S(=O)R ¹³ , -SO ₂ R ¹³ , -SO ₂ N(R ¹² ) ₂ , or -N(R ¹² )SO ₂ R ¹³ ; each R ¹² is independently selected from hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl and 6-membered heteroaryl; or two R ¹² groups are taken together with the N atom to which they are attached to form a N-containing 4- to 6-membered heterocycloalkyl; each R ¹³ is independently selected from C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, 5-membered heteroaryl and 6-membered heteroaryl; wherein 0, 1, or 2 of Y ¹ , Y ² , Y ³ , and Y ⁴ are N; and wherein 0, 1, or 2 of Z ¹ , Z ² , Z ³ , Z ⁴ , and Z ⁵ are N. [00395] In some embodiments, the compound is further selected from a compound described in PCT/US2021/055548, which is herein incorporated by reference in its entirety. [00396] In some embodiments, a compound described herein is used in combination with an immune checkpoint inhibitor. Non-limiting examples of immune checkpoint inhibitors include PD-1 inhibitors (e.g., pembrolizumab sold under the trade name Keytruda, nivolumab sold under the trade name Opdivo, cemiplimab sold under the trade name Libtayo, or dostarlimab sold under the trade name Jemperli), PD-L1 inhibitors (e.g., atezolizumab sold under the trade name Tecentriq, avelumab sold under the trade name Bavencio, durvalumab sold under the trade name Imfinzi, KN035, CK-301, AUNP12, CA-170, or BMS-986189), and CTLA-4 inhibitors (e.g., ipilimumab sold under the trade name Yervoy). In some embodiments, the compound described herein is used in combination with a PD-1 inhibitor. In some embodiments, the compound described herein is used in combination with a PD-L1 inhibitor. In some embodiments, the compound described herein is used in combination with durvalumab, atezolizumab, or avelumab. In some embodiments, the compound described herein is used in combination with durvalumab. In some embodiments, the compound described herein is used in combination with atezolizumab. In some embodiments, the compound described herein is used in combination with avelumab. In some embodiments, the compound described herein is used in combination with a CTLA-4 inhibitor. [00397] The compounds described herein, or a pharmaceutically acceptable salt thereof, as well as combination therapies, are administered before, during or after the occurrence of a disease or condition, and the timing of administering the composition containing a compound varies. Thus, in one embodiment, the compounds described herein are used as a prophylactic and are administered continuously to subjects with a propensity to develop conditions or diseases in order to prevent the occurrence of the disease or condition. In another embodiment, the compounds and compositions are administered to a subject during or as soon as possible after the onset of the symptoms. In specific embodiments, a compound described herein is administered as soon as is practicable after the onset of a disease or condition is detected or suspected, and for a length of time necessary for the treatment of the disease. In some embodiments, the length required for treatment varies, and the treatment length is adjusted to suit the specific needs of each subject. EXAMPLES [00398] As used above, and throughout the description of the invention, the following abbreviations, unless otherwise indicated, shall be understood to have the following meanings: Abbreviations: Pd(OAc) ₂ : palladium(II) acetate; P(o-Tol)3: tri(ortho-tolyl)phosphine; TFA: trifluoroacetic acid; MeCN or CH ₃ CN or ACN: acetonitrile; H ₂ O: water; DMF: dimethylformamide; DCM: dichloromethane; rt: room temperature; hrs: hours; h or hr: hour; min: minute; N: normalily; g: grams mg: milligrams; mL: milliliter; Eq. or equiv: equivalents; mmol: millimole; EtOAc: ethyl acetate; Na2SO4 : sodium sulfate; cat.: catalytic; TBAB: tetra-n-butylammonium bromide; THF: tetrahydrofuran; DME: dimethoxyethane; MeOH: methanol; MsCl: methanesulfonyl chloride or mesyl chloride. [00399] The following examples are provided for illustrative purposes only and not to limit the scope of the claims provided herein. Synthesis of Compounds Example 1. Preparation of Compound 6 [00400] Step 1: To a stirred solution of 3-bromo-2-chloro-6-methylpyridine (I-18) (20.000 g, 1 Eq, 96.866 mmol) in DMF (50 mL), K2CO3 (26.77 g, 2 Eq, 193.73 mmol) was added followed by methyl piperidine-4-carboxylate (25.000 g, 1.8024 Eq, 174.59 mmol) and then the reaction mixture was heated to 140 °C for 15 h. The reaction mixture was allowed to cool to room temperature. To this was added excess ice to fill the flask and stirred for an additional 1.5-2 hrs. A yellow precipitate was formed which was filtered and washed with cold ice water to obtain compound I-19 as a yellow solid (90%). LC-MS: Calculated for C13H17BrN2O2 is 313.19, Observed: 313.0 [M] ⁺ & 315.0 [M+2] ⁺ [00401] Step 2: To a stirred solution of methyl 1-(2-bromo-5-methylphenyl)piperidine-4- carboxylate (I-19) (16.400 g, 1 Eq, 52.529 mmol) in Ethanol (150 mL) was added hydrazine monohydrate (64-65%) (26.31 g, 25.49 mL, 64% Wt, 10 Eq, 525.29 mmol) and heated to 110 °C for ~2.5 hr. The flask was allowed to cool to room temperature which caused the formation of a white solid. The solid was then filtered and washed with cold MeOH followed by triurating with ether. The resultant dry white powder I-20 (95%) was used in the next step without further purification. LC-MS: Calculated for C12H17BrN4O is 312.23 Observed: 312.0 [M] ⁺ & 314.0 [M+2] ⁺ [00402] Step 3: To a stirred solution of 1-(3-bromo-6-methylpyridin-2-yl)piperidine-4- carbohydrazide (I-20) (13.000 g, 1 Eq, 41.51 mmol) was suspended in Acetonitrile (150 mL) and sonicated to dissolve the white solid. To the clear solution sodium bicarbonate (4.184 g, 1.2 Eq, 49.81 mmol) predissolved in ~50 mL of H2O, was added which caused the solution to become cloudy. The reaction mixture was heated in a water bath to help SM dissolve. To this reaction mixture, cyanic bromide (5.276 g, 9.962 mL, 5 molar, 1.2 Eq, 49.81 mmol) was added and the reaction mixutre was allowed to stir for ~1 hr. The mixture was then concentrated and resuspended in CH2Cl2 then filtered to remove solids. The filtrate was then concentrated to give crude I-21 (92%) as thick brown oil which was used in the next step without further purification. LC-MS: Calculated for C ₁₃ H ₁₆ BrN ₅ O is 337.05 Observed: 337.0 [M] ⁺ & 339.05 [M+2] ⁺ [00403] Step 4: To a stirred suspension of 5-(1-(3-bromo-6-methylpyridin-2-yl)piperidin-4- yl)-1,3,4-oxadiazol-2-amine (I-21) (7.39 g, 1 Eq, 21.9 mmol) in 1,4-Dioxane (75 mL) was heated to reflux and 1,1-dimethoxy-N,N-dimethylmethanamine (3.91 g, 4.36 mL, 1.5 Eq, 32.8 mmol) was added during hot condition. The reaction mixture was refluxed for ~2 hrs. LCMS revealed complete conversion to the product. Furthermore, the rxn mixture was concentrated to dryness and used in the next step without further purification. The product I-22 (82%) was observed as a thick viscous brown oil. LC-MS: Calculated for C16H21BrN6O is 392.09 Observed: 392.04 [M] ⁺ & 394.0 [M+2] ⁺ [00404] Step 5: A solution of the crude product (E)-N'-(5-(1-(3-bromo-6-methylpyridin-2- yl)piperidin-4-yl)-1,3,4-oxadiazol-2-yl)-N,N-dimethylformimi damide (I-22) (8.500 g, 1 Eq, 21.61 mmol) in 1,4-Dioxane (100 mL) was added Methylamine (40% in MeOH) (6.713 g, 22.05 mL, 9.8 molar, 10 Eq, 216.1 mmol) and AcOH (3.894 g, 3.712 mL, 3 Eq, 64.84 mmol) then heated to 110 °C overnight. The reaction mixture was then concentrated to dryness and adsorbed in silica gel. The compound was purified using silica gel column eluted with DCM in methanol to obtain the desired compound I-23 (62%) as white solid. LC-MS: Calculated for C ₁₄ H ₁₉ BrN ₆ is 350.08 Observed: 350.08 [M] ⁺ & 352.08 [M+2] ⁺ Representative procedure of Suzuki coupling for Compound 6 [00405] Step 6: To a stirred homogenous solution of 5-(1-(3-bromo-6-methylpyridin-2- yl)piperidin-4-yl)-4-methyl-4H-1,2,4-triazol-3-amine (I-23) (30 mg, 1 Eq, 85.41 µmol) in 1,4- Dioxane (5 mL)Water (0.1 mL) was added (1-propyl-1H-pyrazol-4-yl)boronic acid (I-32 (26.30 mg, 2 Eq, 170.8 µmol), Tetrakis(triphenylphosphine)palladium(0) (9.870 mg, 0.1 Eq, 8.541 µmol) and potassium carbonate (35.41 mg, 3 eq, 256.2 umol). The reaction mixture was then heated to reflux for ~5-6 hrs. The mixture was then extracted with EtOAc. The organic layer is washed with brine, dried (MgSO4) and concentrated to obtain the crude compound. The crude obtained was concentrated then purified via silica gel chromatography eluting 0-20% MeOH in CH ₂ Cl ₂ . The product was then concentrated and repurified via reverse phase chromatography eluting a gradient of 0-100% ACN (+0.1% FA) in H ₂ O (+0.1% FA) to give Compound 6 (52%) as an off white solid. LC-MS: Calculated for C19H22FN7 is 380.50, Observed: 381.2 [M+1] ⁺ [00406] A similar procedure to those provided above was employed to make the compounds shown below by using appropriate boronic acid derivatives along with compound I-23 as shown above.

Example 2: Synthesis of 2-(4-(5-amino-4-methyl-4H-1,2,4-triazol-3-yl)piperidin-1-yl) -3-(6- fluoropyridin-3-yl)benzonitrile (Compound 14) [00407] Step 1: To a stirred solution of 3-bromo-2-fluorobenzonitrile (I-33, 8.5 g, 42.5 mmol) in DMSO (85 mL), were added DIPEA (29.7 mL, 170 mmol) and Methyl piperidine-4- carboxylate (I-2, 13.10 mL, 85 mmol) respectively at RT. The reaction mixture was stirred at 110 °C for 16 h. The progress of the reaction mixture, monitored by TLC (10% EtOAc in Hexane), showed the complete consumption of starting material. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (100 mL X 2). The combined organic layers were washed with brine (150 mL) and dried over anhydrous Na2SO4; concentrated under reduced pressure to get the crude residue. The crude residue was purified by using MPLC (using manually packed SiO ₂ cartridge 230-400 mesh; 5% EtOAc in Hexane) to afford I-34 (8.4 g, 58%) as a pale-yellow solid UPLC-MS: Calculated for C15H17BrN2O2 is 337.22, Observed: 337.0 [M] ⁺ & 339.0 [M+2] ⁺ [00408] Step 2: To a stirred solution of I-34 (8 g, 23.72 mmol) in ethanol (80 mL) at RT, was added dropwise a solution of hydrazine hydrate (75% in water, 15.37 mL, 237 mmol). The reaction mixture was stirred at 90 °C for 16 h. The reaction, monitored by TLC (100% EtOAc), indicated the complete consumption of starting material. The reaction mixture was concentrated under reduced pressure, the resulting crude residue was triturated with Hexane (100 mL) and dried under vacuum to provide I-35 (7.2 g, 94%) as an off-white solid. UPLC-MS: Calculated for C13H15BrN4O is 323.19, Observed: 323.0 [M] ⁺ & 325.0 [M+2] ⁺ [00409] Step 3: To a stirred solution of I-35 (7.2 g, 22.28 mmol) in dioxane (110 mL) and water (30 mL), were added CNBr (7.08 g, 66.8 mmol) and NaHCO ₃ (7.49 g, 89 mmol) at RT under nitrogen atmosphere. The reaction mixture was stirred at RT for 2 h. The reaction mixture, as monitored by UPLC, indicated 64% product formation. The reaction mixture was quenched with 10% NaHCO ₃ solution (200 mL). The solid precipitated was filtered through Büchner funnel and washed with water (200 mL). The solid was further dried under vacuum to afford I- 36 (6.8 g, 88%) as an off-white solid. UPLC-MS: Calculated for C ₁₄ H ₁₄ BrN ₅ O is 348.20, Observed: 348.0 [M] ⁺ & 350.0 [M+2] ⁺ [00410] Step 4: To a stirred solution of I-36 (3.4 g, 9.76 mmol) in dioxane (50 mL) at RT, was added N,N-dimethylformamide dimethyl acetal (2.61 mL, 19.53 mmol) in a dropwise manner under nitrogen atmosphere. The reaction mixture was stirred at 100 °C for 2 h. After complete consumption of starting material, as monitored by TLC (5% MeOH in DCM), the reaction mixture was concentrated under reduced pressure to furnish I-37 (3.8 g, 97%) as a yellow color solid. The crude product itself utilized in the next step without any further purification. UPLC-MS: Calculated for C17H19BrN6O is 403.28, Observed: 403.2 [M] ⁺ & 405.2 [M+2] ⁺ [00411] Step 5: To a 100 mL tinyclave containing a solution of I-37 (3.8 g, 9.42 mmol) in dioxane (30 mL), were added methylamine (25% in MeOH, 32.6 mL, 94 mmol) and AcOH (1.632 mL, 28.3 mmol) at RT and the reaction mixture stirred at 110 °C for 16 h. The reaction mixture, as monitored by UPLC, indicated the complete consumption of starting material. The reaction mixture was concentred under reduced pressure to get the crude residue. The crude residue was purified by using MPLC (using manually packed SiO ₂ cartridge 100-200 mesh; 10% MeOH in DCM) to obtain I-38 (1 g, 30%) as an off-white solid. UPLC-MS: Calculated for C15H17BrN6 is 361.25, Observed: 360.9 [M] ⁺ & 362.9 [M+2] ⁺ [00412] Step 6: To a stirred solution of I-38 (0.1 g, 0.277 mmol) in dioxane (2 mL) and water (0.6 mL), were added (6-fluoropyridin-3-yl)boronic acid (I-6, 0.078 g, 0.554 mmol) and K ₂ CO ₃ (0.115 g, 0.830 mmol) at RT. The reaction mixture was degassed for 5 min with nitrogen before the addition of Pd(dppf)Cl ₂ (10.13 mg, 0.014 mmol) and degassing continued for another 5 min. The reaction mixture was stirred at 100 °C for 16 h. The progress of the reaction mixture, monitored by TLC, showed the complete consumption of starting material. The reaction mixture was passed through celite bed and the bed was further washed with EtOAc (50 mL). The filtrate was washed with water (50 mL) and brine (50 mL); The organic layer was dried over anhydrous Na2SO4, filtered and the filtrate concentrated under reduced pressure to get a crude residue which was purified by using MPLC (using manually packed SiO2 cartridge 230-400 mesh; 10% MeOH in DCM) to afford desired compound Compound 14 (50 mg, 48%) as a grey color solid. LC-MS: Calculated for C ₂₀ H ₂₀ FN ₇ is 377.18, Observed: 378.3 [M+1] ⁺ [00413] A similar procedure to those provided above was employed to make the compounds shown below by using appropriate boronic acid derivatives along with compound I-38 as shown above.

Example 3: Synthesis of 4-(5-amino-4-methyl-4H-1,2,4-triazol-3-yl)piperidin-1-ium chloride (Compound 45) [00414] Step-1 To a stirred solution of ethyl 1-(tert-Butyloxycarbonyl)isonipecotate (I-39, 25 g, 97 mmol) in ethanol (250 mL), was added hydrazine hydrate (59.7 mL, 972 mmol) and the reaction mixture stirred at 80 °C for 8 h. The reaction mixture was concentrated under reduced pressure. To the resulting residue, water (500 mL) was added and extracted with 10% MeOH in DCM (4 x 200 mL). The combined organic layer was washed with water (1 x 350 mL), followed by brine (1 x 350 mL), dried over sodium sulfate, filtered, and the filtrate concentrated under reduced pressure to obtain light brown coloured gummy liquid as a crude (22 g), which was triturated with Hexane ( 200 mL) and MTBE (20 mL ). The solid obtained was filtered and dried under vacuum to I-40 (19 g, 74%) as a white solid. LC MS: Calculated for C ₁₁ H ₂₁ N ₃ O ₃ is 243.16, Observed: 188.0 [MH-56 (tBu)] ⁺ & 229 [[MH-15 (NH)] ⁺ [00415] Step-2: To a stirred solution of I-40 (19 g, 78 mmol) in 1,4-dioxane (76 mL) and water (19.00 mL), at room temperature, were added sodium bicarbonate (6.89 g, 82 mmol) and Cyanogen bromide (8.69 g, 82 mmol). The stirring was continued at same temperature for 2 h.·The reaction was quenched with saturated NaHCO3 solution (500 mL). The precipitated solid was filtered through Buchner funnel. The solid was further washed with hexane (200 mL) and dried under acuum to obtain I-41 (20 g, 93%) as a white solid. LC MS: Calculated for C12H20N4O3 is 268.15, Observed: 269.3 [M+1] ⁺ [00416] Step-3: To a stirred solution of I-41 (30 g, 112 mmol) in 1,4-dioxane (300 mL) at room acuumture, was added N, N-dimethylformamide dimethyl acetal (31.3 mL, 224 mmol) in a dropwise manner. After the completion of addition, the reaction was stirred at 100 °C for 2 h. The reaction mixture was concentrated under reduced pressure to get a white solid (30 g), which was triturated with hexane (100 mL). The solid was filtered through Buchner funnel and dried to obtain I-42 (27 g, 73%) as a white solid. LC MS: Calculated for C15H25N5O3 is 323.20, Observed: 324.4 [M+1] ⁺ [00417] Step-4: To the solution of I-42 (30 g, 93 mmol) in 1,4-dioxane (300 mL) at room temperature, were added methylamine (40% in methanol, 239 mL, 928 mmol) and acetic acid (15.92 mL, 278 mmol) in a dropwise manner. The reaction was stirred in autoclave at 110 °C for 12 hrs. The mixture was the concentrated under reduced pressure to obtain light brown colored gummy solid as a crude mass which was purified by MPLC (neutral alumina; 0 to 10% MeOH in DCM) to get a white solid. The product obtained was triturated with hexane (2 x 10 mL) followed by MTBE (2 x 5 mL) and dried under vacuum to obtain I-43 (10.2 g, 37%) as a white solid. LC MS: Calculated for C ₁₃ H ₂₃ N ₅ O ₂ is 281.19, Observed: 282.2 [M+1] ⁺ [00418] Step-5: To a solution of I-43 in DCM (3 mL), at 0 °C was added 4 M HCl in 1,4- dioxane (0.533 mL, 2.132 mmol) in dropwise manner. The reaction was warmed upto room temperature and the stirring continued for 2 h. The reaction mixture was concentrated under reduced pressure to obtain a light brown coloured solid as a crude mass, which was triturated with MTBE (10 mL). The solid was filtered through Buchner funnel and dried under vacuum to furnish Compound 45 (120 mg, 77%) as a white solid. LC MS: Calculated for C8H15N5 is 181.13, Observed: 182.3 [M+1] ⁺ Example 4: Synthesis of 5-(1-(5-(6-fluoropyridin-3-yl)-2-methylpyrimidin-4-yl)piperi din-4- yl)-4-methyl-4H-1,2,4-triazol-3-amine (Compound 31) [00419] Step-1: To a stirred solution of Compound 45 (577 mg, 2.65 mmol) in acetonitrile (25 mL), was added triethylamine (1 mL, 7.23 mmol) followed by 5-bromo-4-chloro-2- methylpyrimidine (I-44, 500 mg, 2.410 mmol) and the reaction was allowed to stir at room temperature. After 16 h, reaction mixture was concentrated under reduced pressure. So obtained residue was triturated with EtOAc (10 mL), followed by MTBE (10 mL) to get an off-white solid, which was purified by MPLC (neutral alumina; 20% MeOH in DCM) to get I-45 (110 mg, 12%) as a white solid. LC MS: Calculated for C13H18BrN7 is 352.240, Observed: 352.0 [M] ⁺ 354.0 [M+2] ⁺ [00420] Step-2: To a solution of 5-(1-(5-bromo-2-methylpyrimidin-4-yl)piperidin-4-yl)-4- methyl-4H-1,2,4-triazol-3-amine (I-45, 90 mg, 0.256 mmol) in 1,4-dioxane (2 mL) and water (1 mL), were added cesium carbonate (250 mg, 0.767 mmol), (6-fluoropyridin-3-yl)boronic acid (I-3, 72.0 mg, 0.511 mmol) followed by Sphos (10.49 mg, 0.026 mmol). The reaction mixture was purged with N2 gas for 3 min. Palladium(II) acetate (2.87 mg, 0.013 mmol) was added and N2 purging continued for 2 min. The reaction mixture was stirred at 100 °C for 30 min. The reaction was monitored by LCMS. The reaction mixture was filtered through Celite and the filtrate was concentrated under reduced pressure to get a brown solid (500 mg) which was purified by Prep HPLC (NH ₄ HCO ₃ method) to get Compound 31 (36 mg, 37%) as a white solid. LC MS: Calculated for C18H21FN8 is 368.420, Observed: 369.2 [M+H] ⁺ Example 5. Synthesis of 5-(1-(6'-fluoro-6-methyl-[3,3'-bipyridin]-2-yl)piperidin-4-y l)-N,4- dimethyl-4H-1,2,4-triazol-3-amine of (Compound 30) [00421] Step 1: To a stirred solution of 5-(1-(3-bromo-6-methylpyridin-2-yl)piperidin-4-yl)-4- methyl-4H-1,2,4-triazol-3-amine (I-23, 0.4 g, 1.139 mmol) in MeOH (15 mL), were added NaOMe (0.308 g, 5.69 mmol) and paraformaldehyde (0.051 g, 1.708 mmol). The reaction mixture was stirred at RT for 16 h. NaBH4 (0.043 g, 1.139 mmol) was then added to the reaction mixture and stirred at 80 °C for 30 min. The reaction mixture was cooled to RT and concentrated under reduced pressure. The resulting residue was quenched with aqueous 1 M KOH solution (50 mL) and extracted with 10% MeOH in DCM (50 mL X 2). The combined organic layers were washed with brine (50 mL) and dried over anhydrous Na ₂ SO ₄ ; concentrated under reduced pressure to get the crude residue. The crude residue was purified by using silica gel column (10% MeOH in DCM) to afford I-53 (0.25 g, 60%) as a brown color solid. LC-MS: Calculated for C15H21BrN6 is 365.28, Observed: 365.2 [M] ⁺ & 367.2 [M+2] ⁺ [00422] Step 2: To a stirred solution of I-53 (0.25 g, 0.684 mmol) in dioxane (8 mL) and water (2 mL), were added (6-fluoropyridin-3-yl)boronic acid (I-6, 0.193 g, 1.369 mmol) and K2CO3 (0.284 g, 2.053 mmol) at RT. The reaction mixture was degassed for 5 min with nitrogen before the addition of PdCl ₂ (dppf).CH ₂ Cl ₂ adduct (0.028 g, 0.034 mmol). The degassing was continued for another 5 min; The reaction mixture was thenstirred at 100 °C for 16 h. The progress of the reaction mixture, monitored by TLC, showed the complete consumption of starting material. The reaction mixture was passed through Celite bed and the bed was further washed with 10% MeOH in DCM (50 mL). The filtrate was washed with water (50 mL) and brine (50 mL). The organic layer was dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under reduced pressure to get the crude residue. The crude residue was purified by using silica gel column (8% MeOH in DCM) to afford Compound 30 (84 mg, 32%) as an off-white solid. LC-MS: Calculated for C + 20H24FN7 is 381.21, Observed: 382.2 [M+1] Example 6: Synthesis of 2-(4-(5-amino-4-methyl-4H-1,2,4-triazol-3-yl)piperidin-1-yl) -3-(6- fluoropyridin-3-yl)-6-methylbenzonitrile (Compound 50) [00423] Step 1: To a stirred solution of 2,6-dichloro-3-nitrobenzonitrile (I-54, 20 g, 92 mmol) in THF (200 mL) at RT, was added ethyl piperidine-4-carboxylate (I-2, 18 g, 114 mmol). The reaction mixture was stirred at RT for 16 h. The progress of the reaction mixture, as monitored by UPLC, showed 50% product formation. The reaction mixture was concentrated under reduced pressure to get the crude residue. The crude residue was purified by using silica gel column (5% EtOAc in Hexane) to afford I-55 (11g, 35%) as a yellow color solid. LC-MS: Calculated for C ₁₅ H ₁₆ ClN ₃ O ₄ is 337.08, Observed: 338.2 [M+1] ⁺ [00424] Step 2: To a stirred solution of I-55 (9.4 g, 27.8 mmol) in dioxane (60 mL) and water (6 mL), were added trimethylboroxine (50% in THF, 9.42 mL, 33.4 mmol) and K2CO3 (9.62 g, 69.6 mmol) at RT. The reaction mixture was degassed for 5 min with nitrogen before the addition of Pd(PPh ₃ ) ₄ (1.608 g, 1.392 mmol) and the degassing continued for another 5 min. The reaction mixture was stirred at 100 °C for 16 h. The progress of the reaction mixture, monitored by TLC, showed the complete consumption of starting material. The reaction mixture was passed through Celite bed and the bed was further washed with EtOAc (50 mL). The filtrate was concentrated under reduced pressure and the crude residue purified by silica gel column (10% EtOAc in Hexane) to afford I-56 (7.4g, 83%) as a yellow solid. LC-MS: Calculated for C ₁₆ H ₁₉ N ₃ O ₄ is 317.14, Observed: 318.0 [M+1] ⁺ [00425] Step 3: To a stirred solution of I-56 (9 g, 28.4 mmol) in EtOH (75 mL) under nitrogen atmosphere, was added tin(II) chloride dihydrate (19.20 g, 85 mmol) at RT. The reaction mixture was stirred at 80 °C for 3 h. After complete consumption of the starting material, as monitored by TLC, the reaction mixture was concentrated under reduced pressure. The resulting residue was dissolved in water (60 mL) and the pH was adjusted to 8 with 10% aq NaHCO3 (150 mL) solution. The formed suspension was passed through a Celite bed and the bed was further washed with EtOAc (50 mL). The combined filtrate was extracted with EtOAc (500 mL x 2). The combined organic layers were dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude residue was purified by using silica gel column (15% EtOAc in Hexane) to afford I-57 (6.2g, 76%) as an off-white solid. LC-MS: Calculated for C16H21N3O2 is 287.36, Observed: 288.4 [M+1] ⁺ [00426] Step 4: To a stirred solution of I-57 (5 g, 17.40 mmol) in acetonitrile (50 mL) at 0 °C, was added dropwise a cold solution of H ₂ SO ₄ (5 mL) in water (20 mL). The reaction temperature should be carefully maintained within the range of 0–5 °C while addition of a cold solution of NaNO2 (1.801 g, 26.1 mmol) in water (25 mL). The reaction mixture was then stirred at 0 °C for 1 h. The resulting diazonium salt was treated with a cold solution of KI (4.33 g, 26.1 mmol) in water (20 mL) at 0 °C. The reaction mixture was then allowed to stir at RT for 1 h. The progress of the reaction mixture, as monitored by UPLC, showed the 60% product formation. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (100 mL x 2). The combined organic layers were dried over anhydrous Na ₂ SO ₄ ; filtered and the filtrate was concentrated under reduced pressure. The crude residue was purified by using silica gel column (20% EtOAc in Hexane) to afford I-58 (6g, 87%) as a dark brown color solid. LC-MS: Calculated for C ₁₆ H ₁₉ IN ₂ O ₂ is 398.05, Observed: 399.1 [M+1] ⁺ [00427] Step 5: To a stirred solution of I-58 (6 g, 15.07 mmol) in ethanol (60 mL) at RT, was added dropwise a solution of hydrazine hydrate (79% in water, 28.6 mL, 452 mmol). The reaction mixture was stirred at 90 °C for 16 h. The reaction was monitored by TLC (100% EtOAc), indicated complete consumption of the starting material. The reaction mixture was concentrated under reduced pressure, the resulting crude residue triturated with hexane (100 mL) and dried under high vacuum to provide I-59 (6.1g, 77%) as an off-white solid. The crude product was used in the next step without further purification. LC-MS: Calculated for C ₁₄ H ₁₇ IN ₄ O is 384.04, Observed: 385.0 [M+1] ⁺ [00428] Step 6: To a stirred solution of I-59 (6 g, 15.62 mmol) in dioxane (60 mL) and water (8 mL), were added CNBr (5.79 g, 54.7 mmol) and NaHCO3 (5.25 g, 62.5 mmol) at RT under nitrogen atmosphere. The reaction mixture was stirred at RT for 1 h. The reaction mixture, as monitored by UPLC, indicated 60% product formation. The reaction mixture was quenched with 10% NaHCO3 solution (200 mL). The solvent was removed under reduced pressure up to 1/4 ^th of its volume. The solid precipitated was filtered through Büchner funnel and washed with water (200 mL) and hexane (100 mL). The solid was further dried under high vacuum to afford I-60 (5.4g, 85%) as an off-white solid. LC-MS: Calculated for C ₁₅ H ₁₆ IN ₅ O is 409.04, Observed: 410.0 [M+1] ⁺ [00429] Step 7: To a stirred solution of I-60 (2.4 g, 5.86 mmol) in dioxane (20 mL) at RT, was added N,N-dimethylformamide dimethyl acetal (1.57 mL, 11.73 mmol) in a dropwise manner under nitrogen atmosphere. The reaction mixture was stirred at 100 °C for 2 h. After complete consumption of starting material, as monitored by TLC (5% MeOH in DCM), the reaction mixture was concentrated under reduced pressure to furnish I-61 (2.5g, 92%) as an off-white solid. The crude product was used in the next step without further purification. LC-MS: Calculated for C ₁₈ H ₂₁ IN ₆ O is 464.08, Observed: 465.2 [M+1] ⁺ [00430] Step 8: To a solution of I-61 (2.5 g, 5.38 mmol) in dioxane (30 mL), were added methylamine (40% in MeOH, 15 mL, 126 mmol) and AcOH (0.924 mL, 16.15 mmol) at RT and the reaction mixture was stirred at 110 °C for 16 h. The reaction mixture, monitored by TLC, indicated the complete consumption of starting material. The reaction mixture was concentrated under reduced pressure to get the crude residue. The crude residue was purified by using silica gel column (9% MeOH in DCM) to obtain I-62 (530 mg, 23%) as an off-white solid. LC-MS: Calculated for C ₁₆ H ₁₉ IN ₆ is 422.07, Observed: 423.0 [M+1] ⁺ [00431] Step 9: To a stirred solution of I-62 (300 mg, 0.710 mmol) in dioxane (5 mL) and water (1 mL), were added (6-fluoropyridin-3-yl) boronic acid (I-6, 200 mg, 1.421 mmol) and K ₂ CO ₃ (295 mg, 2.131 mmol) at RT. The reaction mixture was degassed for 5 min with nitrogen before the addition of Pd(dppf)Cl ₂ .CH ₂ Cl ₂ adduct (29.0 mg, 0.036 mmol) and the degassing continued for another 5 min. The reaction mixture was stirred at 100 °C for 16 h. The reaction mixture was passed through Celite bed and the bed was further washed with EtOAc (50 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ , filtered and the filtrate was concentrated under reduced pressure. The crude residue was purified by reversed-phase preparative HPLC eluting 5~100% ACN (0.1% NH4OH) in H2O (0.1% NH4OH) to afford Compound 50 (30 mg, 11%) as an off-white solid. LC-MS: Calculated for C ₂₁ H ₂₂ FN ₇ is 391.19, Observed: 392.1 [M+1]+ Example 7: Synthesis of 5-(1-(5-(6-fluoropyridin-3-yl)-2-methoxypyrimidin-4-yl)piper idin- 4-yl)-4-methyl-4H-1,2,4-triazol-3-amine (Compound 58) [00432] Step 1: To a solution of 5-bromo-2,4-dichloropyrimidine (I-63, 0.5 g, 2.194 mmol) in DMF (25 mL), were added potassium carbonate (1.213 g, 8.78 mmol) and 4-methyl-5- (piperidin-4-yl)-4H-1,2,4-triazol-3-amine.HCl (compound 45, 0.6 g, 2.414 mmol) and stirred at room temperature for 2 h. The reaction was quenched with ice cold water (50 mL). The precipitated solid was filtered through Buchner funnel and dried under vacuum to furnish I-64 (0.7g, 83%) as an off-white solid. LC-MS: Calculated for C ₁₂ H ₁₅ BrClN ₇ is 372.6; observed: 372.0 [M] ⁺ and 374.0 [M+2] ⁺ [00433] Step 2: To a stirred solution of I-64 (0.4 g, 1.04 mmol) in MeOH (10 mL), at 0 °C, sodium methoxide (25% in methanol; 0.45 mL, 2.082 mmol) was added in dropwise manner. The reaction mixture was heated at 50 °C for 1 h. The reaction mixture was concentrated under reduced pressure to provide the crude material. To the resulting residue water (10 mL) was added and extracted with DCM (3 x 50 mL). The combined organic layer was washed with brine (15 mL), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The resulting crude was purified by silica gel column (10% MeOH in DCM) to obtain I-65 (0.3 g, 74%) as a light yellow solid. LC-MS: Calculated for C ₁₃ H ₁₈ BrN ₇ O is 368.2; observed: 368.2 [M] ⁺ and 370.0 [M+2] ⁺ [00434] Step 3: To a stirred solution of I-65 (0.3 g, 0.77 mmol) in 1,4-dioxane (20 mL), water (10 mL), were added (6-fluoropyridin-3-yl) boronic acid (I-6, 0.21 g, 1.54 mmol), and cesium carbonate (0.75 g, 2.32 mmol) at 25 °C. The reaction mixture was purged with nitrogen for 5 min. Then palladium(II) acetate (9.0 mg, 0.039 mmol) and SPhos (0.032 g, 0.077 mmol) were introduced and purging continued for 2 min. The vial was sealed and irradiated at 100 °C for 45 min in a microwave reactor. The reaction mixture was filtered through celite bed and washed with 1,4-dioxane (10 mL). The filtrate was evaporated under reduced pressure to obtain crude material, which was purified by silica gel column (10% MeOH in DCM) to obtain Compound 58 (48 mg, 15) as off-white solid. LC-MS: Calculated for C18H21FN8O is 384.4; observed: 385.2 [M+1] ⁺ Example 8: Synthesis of 5-(1-(4-(6-fluoropyridin-3-yl)-1-methyl-1H-pyrazol-3-yl)pipe ridin- 4-yl)-4-methyl-4H-1,2,4-triazol-3-amine (Compound 46) [00435] Step 1: To a stirred solution of ethyl piperidine-4-carboxylate (I-2, 49.0 mL, 318 mmol) in a mixture of THF (750 mL) and water (750 mL), were added Cs ₂ CO ₃ (124 g, 382 mmol) and benzyl chloroformate (35% in toluene, 184 mL, 382 mmol) at RT. The reaction mixture was stirred at RT for 16 h. After complete consumption of starting material, as monitored by TLC (30% EtOAc in Hexane), the reaction mixture was concentrated under reduced pressure. The residue was diluted with water (200 mL) and extracted with EtOAc (250 mL X 2). The combined organic layers were washed with brine (150 mL) and dried over anhydrous Na ₂ SO ₄ ; filtered and concentrated under reduced pressure to obtain I-66 (90g, 97%) as a pale yellow liquid. [00436] Step 2: To a stirred solution of I-66 (40 g, 137 mmol) in ethanol (400 mL) at RT, was added hydrazine hydrate (68.7 g, 1373 mmol). The reaction mixture was stirred at 90 °C for 16 h. The reaction, monitored by TLC (30% EtOAc in Hexane), indicated the complete consumption of starting material. The reaction mixture was concentrated under reduced pressure, the resulting crude residue was triturated with hexane (100 mL) and dried under high vacuum to provide I-67 (35g, 92%) as an off-white solid. The crude product itself utilized in the next step without any further purification. LC-MS: Calculated for C + 14H19N3O3 is 277.32, Observed: 278.3 [M+1] [00437] Step 3: To a stirred solution of I-67 (30 g, 108 mmol) in dioxane (480 mL) and water (120 mL), were added CNBr (34.4 g, 325 mmol) and NaHCO ₃ (36.3 g, 433 mmol) at RT under nitrogen atmosphere. The reaction mixture was stirred at RT for 2 h. The reaction mixture, as monitored by UPLC, indicated 72% product formation. The reaction mixture was quenched with 10% NaHCO3 solution (600 mL). The solvent was removed under reduced pressure up to 1/4 ^th of its volume. The solid precipitated was filtered through Büchner funnel and washed with water (600 mL) and hexane (250 mL). The solid was further dried under high vacuum to afford I-68 (20.1g, 61%) as an off-white solid. LC-MS: Calculated for C ₁₅ H ₁₈ N ₄ O ₃ is 302.33, Observed: 303.2 [M+1]+ [00438] Step 4: To a stirred solution of I-68 (40 g, 132 mmol) in dioxane (400 mL) at RT, was added N,N-dimethylformamide dimethyl acetal (35.4 mL, 265 mmol) in a dropwise manner under nitrogen atmosphere. The reaction mixture was stirred at 100 °C for 2 h. After complete consumption of starting material, the reaction mixture was concentrated under reduced pressure to furnish I-69 (47.5g, 99%) as a brown color gummy compound. LC-MS: Calculated for C H N O is 357. + 18 23 5 3 41, Observed: 358.2 [M+1] [00439] Step 5: In an autoclave containing a solution of I-69 (47.5 g, 133 mmol) in dioxane (500 mL), were added methylamine (25% in MeOH, 454 mL, 2889 mmol) and AcOH (22.80 mL, 399 mmol) at RT and the reaction mixture stirred at 110 °C for 16 h. The reaction mixture was concentred under reduced pressure to get the crude residue. The crude residue was purified by using silica gel column (MeOH in DCM) to obtain I-70 (17g, 41%) as a pale-yellow compound. LC-MS: Calculated for C ₁₆ H ₂₁ N ₅ O ₂ is 315.38, Observed: 316.1 [M+1]+ [00440] Step 6: To a stirred solution of I-70 (17 g, 53.9 mmol) in THF (200 mL) at RT, were added Et3N (22.73 mL, 162 mmol), DMAP (1.317 g, 10.78 mmol) and Boc2O (18.58 mL, 81 mmol) under nitrogen atmosphere. The reaction, monitored by TLC, indicated the complete consumption of starting material. The reaction mixture was diluted with water (500 mL) and extracted with EtOAc (500 mL X 2). The combined organic layers were washed with brine (300 mL), dried over anhydrous Na2SO4; filtered and concentrated under reduced pressure to get the crude residue. The crude residue was purified by using silica gel column (5% MeOH in DCM) to obtain I-71 (7g, 31%) as an off-white solid. LC-MS: Calculated for C H + 21 29N5O4 is 415.49, Observed: 416.5 [M+1] [00441] Step 7: In a mini-clave, to a stirred solution of I-71 (8.5 g, 20.46 mmol) in MeOH (100 mL) under nitrogen atmosphere, was added 10% Pd/C (1.742 g, 1.637 mmol) at RT. The reaction mixture was stirred under H2 atmosphere at 60 psi for 16 h. The progress of the reaction mixture, monitored by TLC (10% MeOH in DCM), showed the complete consumption of starting material. The reaction mixture was filtered through Celite bed and the bed was further washed with MeOH (500 mL). The filtrate was concentrated under reduced pressure and dried under high vacuum to afford I-72 (5.4g, 93%) as a pale yellow solid. LC-MS: Calculated for C H N O is 2 + 13 23 5 2 81.19, Observed: 282.2 [M+1] [00442] Step 8: To a mixture of I-72 (0.5 g, 1.777 mmol; SYE2102515-35) and 3-iodo-1- methyl-1H-pyrazole (I-73, 1.109 g, 5.33 mmol) in THF (10 mL), was added sodium tert- butoxide (0.683 g, 7.11 mmol), and purged with nitrogen for 8 min. Then t-BuXPhos Pd G3 (0.424 g, 0.533 mmol) was introduced, and the reaction mixture was irradiated with Biotage microwave initiator at 100 °C temperature for 30 min. The reaction was quenched with water (60 mL) and extracted with 20% MeOH in DCM (3 x 60 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to get light brown gum, which was triturated with MTBE (20 mL) to afford I-74 (640 mg, 45%) as light brown solid. LC MS: Calculated for C17H27N7O2 is 361.45; Observed 362.2 [M+1] ⁺ [00443] Step 9: To a stirred solution of I-74 (0.6 g, 0.747 mmol) in DMF (5 mL), was added NIS (0.176 g, 0.784 mmol) at room temperature and the reaction mixture stirred under nitrogen at the same temperature for 1 h. At this stage, TLC indicated formation of a non-polar spot with the consumption of Starting material (Rf = 0.2; 5% MeOH in DCM; UV active). The reaction mixture was concentrated and triturated with water (30 mL) to obtain the crude residue as yellow solid, which was purified by silica gel column (5% MeOH in DCM) to afford I-75 (390 mg, 44%) as yellow solid. LC MS: Calculated for C17H26IN7O2 is 487.34; Observed 488.2 [M+1] ⁺ [00444] Step 10: To a solution of I-75 (0.39 g, 0.328 mmol) in a mixture of 1,4-dioxane and water (10 mL: 2 mL), were added (6-fluoropyridin-3-yl)boronic acid (5, 0.092 g, 0.656 mmol) and Cs2CO3 (0.321 g, 0.984 mmol), and the resulting mixture purged with nitrogen for 5 min. Then, SPhos (0.013 g, 0.033 mmol) and palladium(II) acetate (3.68 mg, 0.016 mmol) were introduced. The vial was sealed, and the reaction mixture irradiated in a microwave irradiator at 100 °C for 30 min. The reaction mixture was concentrated and triturated with water (10 mL) to obtain the crude residue as light brown solid, which was purified by reversed phase prep HPLC (Eluents: A: 0.1% HCOOH in water, B: ACN, 20−60% B) to afford Compound 46 (27 mg, 22%) as white fluffy solid. LC MS: Calculated for C17H21FN8 is 356.41; Observed 357.2 [M+1] ⁺ Example 9: Synthesis of 5-(1-(4'-fluoro-4-methyl-[1,1'-biphenyl]-2-yl)piperidin-4-yl )-4- methyl-4H-1,2,4-triazol-3-amine (Compound 53) [00445] Step-1: To a mixture of I-44 (5.0 g, 17.77 mmol) in THF (70 mL), was added LiHMDS (1.0 M in THF; 35.5 mL, 35.5 mmol) in dropwise manner at -78 °C. After 30 min, Cbz-Cl (7.58 mL, 53.3 mmol) was added in dropwise manner. The reaction was stirred at room temperature for 16 h. The reaction was quenched with the addition of saturated ammonium chloride solution (100 mL) and extracted with EtOAc (2 x 150 mL). The combined organic layer was washed with brine (150 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude residue was purified by using silica gel column (1% MeOH in DCM) to afford I-76 (2.7 g, 34%) as a yellow solid. LCMS: Calculated for C21H29N5O4 is 415.49, Observed: 416.2 [M+1] ⁺ [00446] Step-2: To a suspension of I-76 (2.7 g, 6.50 mmol) in DCM (30 mL), was added HCl (4 M in 1,4-dioxane; 4.87 mL, 19.49 mmol) in dropwise manner at 0 °C. The reaction mixture was warmed up to room temperature and the stirring continued for 1 h. The reaction was concentrated under reduced pressure to obtain light brown colored solid, which was triturated with MTBE (50 mL). The solid was filtered through Buchner funnel and dried under vacuum to get I-77 (2.3 g, 96%) as a white solid. LCMS: Calculated for C16H22ClN5O2+ is 316.38, Observed: 316.2 [M] ⁺ [00447] Step-3: To a suspension of I-77 (2.268 g, 6.45 mmol) in DMSO (20 mL), were added t-BuOK (2.170 g, 19.34 mmol) followed by 2-fluoro-4-methyl-1-nitrobenzene (I-78, 1g, 6.45 mmol) at room temperature under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 16 h. The reaction was quenched with ice cold water (100 mL). The precipitated solid was filtered off and dried under vacuum. The resulting solid was purified by using silica gel column (2% MeOH in DCM) to afford I-79 (1.5 g, 46%) as a yellow solid. LCMS: Calculated for C23H26N6O4 is 450.49, Observed: 451.2 [M+1] ⁺ [00448] Step-4: To a suspension of I-79 (1.5 g, 3.33 mmol) in MeOH (20 mL), were added zinc (1.306 g, 19.98 mmol) and ammonium chloride (2.137 g, 40.0 mmol) in portion wise manner at room temperature. The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was filtered through the celite pad and washed with MeOH (100 mL). The filtrate was concentrated under reduced pressure. The resulting crude residue was triturated with MTBE (20 mL) and dried under vacuum to get I-80 (1.3g, 73%) as a yellow solid. LCMS: Calculated C23H28N6O2 is 420.52, Observed: 421.2 [M+1] ⁺ [00449] Step-5: To a stirred solution of I-80 (500 mg, 0.939 mmol) in DCM: water (5:3; 8 mL), were added a solution of sodium nitrite (324 mg, 4.70 mmol) in water (2 mL) followed by diiodomethane (0.152 mL, 1.879 mmol) in dropwise manner at room temperature. After 10 min, a solution acetic acid (1.075 mL, 18.79 mmol) was added. The reaction mixture was stirred at same temperature for 16 h. The reaction was quenched with water (50 mL) and extracted with DCM (2 x 50 mL). Combined organic layer was washed with brine (50 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude residue was purified by using silica gel column (50% EtOAc in hexane) to afford I-81 (100 mg, 19%) as a white solid. LCMS: Calculated for C23H26IN5O2 is 531.39, Observed: 532.0 [M+1] ⁺ [00450] Step-6: To a stirred solution of I-81 (90 mg, 0.169) in 1,4-dioxane (2 mL), were added cesium carbonate (110 mg, 0.339 mmol) and (4-fluorophenyl)boronic acid (I-82, 35.5 mg, 0.254 mmol) at room temperature. The reaction mixture was purged with nitrogen gas for 5 min. Then tetrakis(triphenylphosphine)palladium(0) (19.57 mg, 0.017 mmol) was added and reaction was stirred at 90 °C for 16 h. The reaction was diluted with EtOAc (20 mL), filtered through the celite pad and washed with EtOAc (20 mL). The filtrate was concentrated under reduced pressure. The resulting crude residue was purified by preparative TLC (eluted 3 times; 3% MeOH in DCM) to afford Compound 53 (12 mg, 18%) as an off-white solid. LCMS: Calculated for C21H24FN5 is 365.45, Observed: 366.4 [M+1] ⁺ Example 10: Synthesis of 5-(1-(2-(6-fluoropyridin-3-yl)-5-methylphenyl)piperidin-4-yl )-4- methyl-4H-1,2,4-triazol-3-amine (Compound 52) [00451] Step-1: To a stirred solution of I-83 (120 mg, 0.208) in 1,4-dioxane (2 mL), were added cesium carbonate (135 mg, 0.416 mmol) and (6-fluoropyridin-3-yl) boronic acid (I-6, 43.9 mg, 0.312 mmol) at room temperature and purged with N2 gas for 5 min. Then tetrakis(triphenylphosphine)palladium (0) (24.01 mg, 0.021 mmol) was introduced to the reaction and the reaction mixture stirred at 90 °C for 16 h. The reaction was diluted with EtOAc (20 mL) and filtered through a Celite pad. The pad was washed with EtOAc (20 mL). The combined filtrate was concentrated under reduced pressure to get the crude residue, which was purified by reversed phase preparative HPLC (Eluents: A:10 mM ammonium bicarbonate, B: ACN) to afford Compound 52 (4.6 mg, 5%) as an off-white solid. LCMS: Calculated for C20H23FN6 is 366.4, Observed: 367.2 [M+1] ⁺ Example 11: Synthesis of 5-(2-(4-(5-amino-4-methyl-4H-1,2,4-triazol-3-yl)piperidin-1- yl)-4- methylphenyl)pyrimidin-2-amine (Compound 57) [00452] Step-1: To a stirred solution of I-83 (150 mg, 0.260 mmol; SYE2103221-30) in 1,4- dioxane (2 mL) and H2O (0.5 mL) were added potassium carbonate (108 mg, 0.779 mmol) and (2-aminopyrimidin-5-yl)boronic acid (2, 72.2 mg, 0.52 mmol) at room temperature and purged with nitrogen gas for 5 min. To this reaction mixture PdCl2(dppf).CH2Cl2 (10.6 mg, 0.013 mmol) was added. The reaction mixture was stirred at 100 °C for 16 h. The reaction was diluted with EtOAc (30 mL), filtered through a Celite pad and washed with EtOAc (30 mL). The filtrate was concentrated under reduced pressure to give crude product, which was purified by reversed phase preparative HPLC (Eluents: 0.1% formic acid in water and ACN) to afford Compound 57 (4 mg, 2%) as an off-white solid. LCMS: Calculated for C19H24N8 is 364.46, Observed: 365.3 [M+1] ⁺ Example 12: Synthesis of 4-(4-(5-amino-4-methyl-4H-1,2,4-triazol-3-yl)piperidin-1-yl) -5-(6- fluoropyridin-3-yl)pyrimidin-2-amine (Compound 33) [00453] Step-1: To a stirred suspension of compound 45 (2.327 g, 10.69 mmol) in DMF (45 mL), were added TEA (2.82 mL, 20.04 mmol) and 5-bromo-4-chloro-2-(methylthio)pyrimidine (I-85, 1.6 g, 6.68 mmol) at room temperature under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 16 h. After completion, the reaction mixture was filtered through Buchner funnel. The obtained solid was triturated with MTBE (250 mL x 2) and dried under vacuum to obtain I-86 (4.2 g, 82%) as a white solid. LC MS: Calculated for C13H18BrN7S is 384.30, Observed: 384.0 [M] ⁺ and 386.0 [M+2] ⁺ [00454] Step-2: To a stirred solution of I-86 (1.4 g, 1.821 mmol) in a mixture of 1,4-dioxane (8 mL) and water (4 mL), were added (6-fluoropyridin-3-yl)boronic acid (I-6, 0.513 g, 3.64 mmol) and cesium carbonate (1.780 g, 5.46 mmol) at room temperature. The reaction mixture was purged with nitrogen for 5 min. To this reaction mixture, palladium(II) acetate (0.020 g, 0.091 mmol) and SPhos (0.075 g, 0.182 mmol) were introduced and the purging continued for 2 min. The reaction mixture was irradiated at 100 °C for 45 min in microwave reactor. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The crude mass thus obtained was dissolved in 10% MeOH in DCM (50 mL) and filtered through Celite bed. The bed was further washed with 10% MeOH in DCM (100 mL) and the filtrate concentrated under reduced pressure to get I-87 (600 mg). [00455] LC MS: Calculated for C18H21FN8S is 400.48, Observed: 401.0 [M+H] ⁺ [00456] Step-3: To a stirred solution of I-87 (800 mg, 1.758 mmol) in THF (9.0 mL), was added a solution of oxone (2161 mg, 3.52 mmol) in water (5 mL) at room temperature. After stirring for 2 h, the reaction mixture was concentrated under reduced pressure at 30 ^o C. The crude residue was purified by reverse phase column chromatography (Eluents: A: 10 mM ammonium bicarbonate, B: ACN [6:4 ratio of A:B]) to obtain I-88 (300 mg, 37%) as an off- white solid. LC MS: Calculated for C18H21FN8O2S is 432.47, Observed: 433.1 [M+H] ⁺ [00457] Step-4: To a stirred solution of I-88 (150 mg, 0.347 mmol) in a mixture of 1,4-dioxane (4 mL) and t-BuOH (0.2 mL), was added 25% ammonia solution in water (3.24 mL, 34.7 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 72 h. The reaction mixture was concentrated under reduced pressure. to obtain crude residue, which was purified by reverse phase preparative HPLC (Eluents: 10 mM ammonium acetate in water and acetonitrile) to obtain Compound 33 (7 mg, 5%) as an off-white solid. LC MS: Calculated for C17H20FN9 is 369.40, Observed: 370.1 [M+H] ⁺ Example 13: Synthesis of 5-(1-(2-fluoro-5-(6-fluoropyridin-3-yl)pyrimidin-4-yl)piperi din-4- yl)-4-methyl-4H-1,2,4-triazol-3-amine (Compound 60) [00458] To a solution of I-88 (0.2 g, 0.45 mmol) in DMF (5.0 mL), was added CsF (278 mg, 1.831 mmol) and heated to 100 °C for 2 h. The reaction mass was evaporated under reduced pressure at 30 °C bath temperature. The crude residue thus obtained was dissolved in acetonitrile (1.5 mL), water (1.5 mL) and purified over reverse phase column chromatography (Eluents:A:10 mM Ammonium Bicarbonate in water, B:ACN) to get Compound 60 (53 mg, 30%) as an off white solid. LC-MS: Calculated for C17H18F2N8 is 372.3; observed: 373.2 [M+1] ⁺ Example 14: Synthesis of 4-(4-(5-amino-4-methyl-4H-1,2,4-triazol-3-yl)piperidin-1-yl) -5-(6- fluoropyridin-3-yl)pyrimidine-2-carbonitrile (Compound 56) [00459] To a stirred solution of I-88 (80 mg, 0.185 mmol) in DMSO (5 mL) was added sodium cyanide (13.60 mg, 0.277 mmol) at 10 °C under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 2 h. After completion of the reaction, the reaction was quenched with water (20 mL) and extracted with 10% MeOH in DCM (2 x 30 mL). The combined organic layer was dried over anhydrous sodium sulphate, filtered and concentrated to obtain crude residue, which was purified by reverse phase column chromatography (Eluents: A: 10 mM ammonium bicarbonate, B: ACN [6:4 ratio of A:B]) to obtain Compound 56 (36 mg, 50%) as an off-white solid. LC MS: Calculated for C18H18FN9 is 379.40, Observed: 380.0 [M+H] ⁺ Example 15: Synthesis of 5-(1-(3-(6-fluoropyridin-3-yl)-6-methylpyrazin-2-yl)piperidi n-4- yl)-4-methyl-4H-1,2,4-triazol-3-amine (Compound 32) [00460] Step 1: To a stirred solution of tert-butyl (4-methyl-5-(piperidin-4-yl)-4H-1,2,4- triazol-3-yl)carbamate (I-72, 1 g, 3.55 mmol) and 3,5-dichloro-2-iodopyrazine (I-89, 1.172 g, 4.26 mmol) in DMSO (15 mL) under nitrogen atmosphere, was added cesium fluoride (1.080 g, 7.11 mmol) at 0 °C. The reaction mixture was allowed to stir at RT for 2 h. After complete consumption of starting material, as monitored by TLC, the reaction mixture was diluted with cold water (20 mL) and extracted with EtOAc (100 mL x 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure to get the crude residue. The crude residue was purified by using silica gel column (50% EtOAc in Hexane to 100% EtOAc) to provide I-90 (420 mg, 23%) as a pale- yellow solid. LC-MS: Calculated for C ₁₇ H ₂₃ ClIN ₇ O ₂ is 519.77, Observed: 520.3 [M] ⁺ and 522.3 [M+2] ⁺ [00461] Step 2: To a stirred solution of I-90 (370 mg, 0.712 mmol) in dioxane (8 mL) and water (2 mL), were added (6-fluoropyridin-3-yl)boronic acid (I-6, 201 mg, 1.424 mmol) and K2CO3 (295 mg, 2.136 mmol) at RT. The reaction mixture was degassed for 5 min with nitrogen before the addition of PdCl ₂ (dppf) (26.0 mg, 0.036 mmol) and the degassing continued for another 5 min. The reaction mixture was stirred at 80 °C for 12 h. The reaction mixture was then passed through Celite bed and the bed was further washed with EtOAc (100 mL). The combined filtrate was washed with water (30 mL) and brine (30 mL). The organic layer was dried over anhydrous Na ₂ SO ₄ , filtered and the filtrate concentrated under reduced pressure. The crude residue was purified by silica gel column (10% MeOH (premixed with 1% Et3N) in DCM) to obtain I-91 (180 mg, 64%) as a brown color solid. LC-MS: Calculated for C ₁₇ H ₁₈ ClFN ₈ is 388.84, Observed: 389.2 [M] ⁺ and 391.2 [M+2] ⁺ [00462] Step 3: To a stirred solution of I-91 (140 mg, 0.360 mmol) in dioxane (5 mL) and water (1.25 mL), were added trimethylboroxine (50% in THF, 0.152 mL, 0.540 mmol) and K ₂ CO ₃ (149 mg, 1.080 mmol) at RT. The reaction mixture was degassed for 5 min with nitrogen before the addition of Pd(PPh ₃ ) ₄ (83 mg, 0.072 mmol) and the degassing continued for another 5 min. The reaction mixture was stirred at 120 °C for 16 h. The progress of the reaction mixture, monitored by TLC, showed the complete consumption of starting material. The reaction mixture was passed through Celite bed and the bed was further washed with EtOAc (50 mL). The filtrate was washed with water (30 mL) and brine (30 mL). The organic layer was dried over anhydrous Na2SO4, filtered and the filtrate concentrated under reduced pressure. The crude residue was purified by reversed-phase preparative HPLC (Eluents: (A) 10 mM NH ₄ HCO ₃ in water and (B) acetonitrile, 40-50%) to afford Compound 32 (18 mg, 13%) as a white solid. LC-MS: Calculated for C H FN is 3 + 18 21 8 68.19, Observed: 369.3 [M+1] Example A-1: Parenteral Pharmaceutical Composition [00463] To prepare a parenteral pharmaceutical composition suitable for administration by injection (subcutaneous, intravenous), 1-100 mg of a water-soluble salt of a compound Formula (A), or a pharmaceutically acceptable salt or solvate thereof, is dissolved in sterile water and then mixed with 10 mL of 0.9% sterile saline. A suitable buffer is optionally added as well as optional acid or base to adjust the pH. The mixture is incorporated into a dosage unit form suitable for administration by injection. Example A-2: Oral Solution [00464] To prepare a pharmaceutical composition for oral delivery, a sufficient amount of a compound of Formula (A), or a pharmaceutically acceptable salt thereof, is added to water (with optional solubilizer(s),optional buffer(s) and taste masking excipients) to provide a 20 mg/mL solution. Example A-3: Oral Tablet [00465] A tablet is prepared by mixing 20-50% by weight of a compound of Formula (A), or a pharmaceutically acceptable salt thereof, 20-50% by weight of microcrystalline cellulose, 1-10% by weight of low-substituted hydroxypropyl cellulose, and 1-10% by weight of magnesium stearate or other appropriate excipients. Tablets are prepared by direct compression. The total weight of the compressed tablets is maintained at 100 -500 mg. Example A-4: Oral Capsule [00466] To prepare a pharmaceutical composition for oral delivery, 10-500 mg of a compound of Formula (A), or a pharmaceutically acceptable salt thereof, is mixed with starch or other suitable powder blend. The mixture is incorporated into an oral dosage unit such as a hard gelatin capsule, which is suitable for oral administration. [00467] In another embodiment, 10-500 mg of a compound of Formula (A), or a pharmaceutically acceptable salt thereof, is placed into Size 4 capsule, or size 1 capsule (hypromellose or hard gelatin) and the capsule is closed. Example B-1: Glutaminyl-peptide cyclotransferase like (QPCTL) Activity Assays [00468] Purified Protein Inhibition (IC50): Glutaminyl-peptide cyclotransferase like (QPCTL) protein activity was determined using L-glutamine-7-amido-4-methylcoumarin (Gln- AMC, Santa Cruz Biotechnology) as a substrate. A second enzyme, pyroglutamyl aminopeptidase (pGAPase, Qiagen), was included in the assay to release the AMC fluorophore following cyclization; appropriate controls were run to ensure that inhibitors were not inhibiting the auxiliary enzyme. Inhibitors were added at various concentrations to buffer (final concentrations: 1 nM QPCTL, 50 mM MES pH 7.0, 10 µM ZnCl2, 0.3 U/mL pGAPase) and the reaction initiated by the addition of Gln-AMC (100 µM final concentration). Reactions became linear after a 10-minute equilibration period at 30 ºC (to accumulate pGlu-AMC intermediate), and were monitored for an additional 10 minutes. [00469] Cellular Efficacy (EC50): Inhibition of QPCTL in a cellular context was determined using 5K A549 cells were plated on to clear 96-well plates in a 100µL volume (50K cells/mL). 24 hours later, 10µL of 10X inhibitor in DMEM was added to cells to incubate in for 48 hours. Cells were washed with 1X DPBS (no Ca, no Mg) and lifted with 20µL of Trypsin/EDTA. 200µL of cell staining buffer (BioLegend) were added and samples split in two 96-well round bottom wells for staining with either with CD47 CC2C6 or B6H12 Ab clones (four wells for control A549 cells to incorporate IgG controls) spun and washed with 200µL of cell staining buffer. Anti-CD47 antibodies CC2C6-APC (Biolegend) and B6H12-APC (Thermo eBioscience) or corresponding Control IgG were diluted 1:80 in cell staining buffer and 100µL were added to wells and incubated 15 min at 4°C in the dark. Plates were spun down, buffer removed, and washed with 200µL of new cell staining buffer. The pellet was suspended in 100µL of cell staining buffer and the cells analyzed using BD Accuri C6 Plus flow cytometer and FLOWJO v10 software. [00470] Table A provides QPCTL IC50 and EC50 values of illustrative compounds. IC50: A < 1 µM; 1 µM ≤ B < 10 µM; 10 µM ≤ C ≤ 50 µM; D > 50 µM EC ₅₀ : A < 1 µM; 1 µM ≤ B < 10 µM; 10 µM ≤ C ≤ 50 µM; D > 50 µM Table A: Representative QPCTL Activity

[00471] The examples and embodiments described herein are for illustrative purposes only and various modifications or changes suggested to persons skilled in the art are to be included within the spirit and purview of this application and scope of the appended claims.