Ether-À-go-go 1 (EAG1) potassium channel inhibitors and uses thereof

Abstract

The disclosure provides methods for the treatment of disorders associated with an increase in potassium channel activity using small molecule inhibitors, such as compounds that selectively bind to a Per-Arnt-Sim (PAS) domain of Ether-à-go-go 1 (EAG1) potassium channels. The disclosure also features pharmaceutical compositions comprising therapeutically effective amounts of the disclosed small molecule inhibitors.

Description

Attorney Docket No.: 0G2440- 1532676 (095WO1)ETHER- A-GO-GO 1 (EAG1) POTASSIUM CHANNEL INHIBITORS AND USES THEREOF CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of and priority to U. S. Provisional Application No. 63 / 733,866, filed on December 13, 2024, which is hereby incorporated by reference in its entirety.STATEMENT REGARDING FEDERALLY FUNDED RESEARCH

[0002] This invention was made with governmental support under CA252969 and GM124020 awarded by the National Institutes of Health, and BI0220104 awarded by National Science Foundation. The government has certain rights in the invention.FIELD

[0003] The disclosure relates to small molecule inhibitors and methods of treating patients with increased potassium channel activity.BACKGROUND

[0004] Ether-a-go-go (EAG) channels are voltage gated potassium ion channel proteins vital to maintaining cellular health. In general, they function by allowing potassium ions to flow out of the cell; thereby, maintaining ion concentration homeostasis. In particular, EAG1 has been shown to be a key regulator of neuronal excitability, and is important for signaling and neurological function. Therefore, genetic mutations, e.g., gain-of-function genetic mutations, in EAG channels are associated with neurological disorders. Additionally, EAG channels are often upregulated in cancer-making inhibition clinically relevant for controlling cancer cell proliferation. Both mutation in and upregulation of EAG1 can lead to increased potassium channel activity, i.e., excessive potassium ion efflux from the cell which may result in hyperpolarization of the membrane potential, leading to disruption of cellular function.

[0005] EAG channels contain an N-terminal Per-Amt-Sim (PAS) domain in their intracellular N-terminal region. The PAS domain is structurally similar to the PAS domain in non-ion channel proteins, which frequently function as ligand binding domains. Therefore, development of small molecule inhibitors capable of binding to the PAS domain of EAG channels is clinically relevant for the treatment of disease states associated with an increase of potassium channel activity.US2008323311601SUMMARY

[0006] Several neurological disorders and developmental abnormalities are associated with genetic mutations in EAG channels. Many of these mutations have been characterized as gain-of-function mutations. Therefore, EAG1 channel inhibitors are a potential treatment. Additionally, EAG1 channels are known oncogenic channels. While almost exclusively expressed in the brain, EAG channels are often upregulated in a majority of primary' human cancers studied. Inhibition of EAG1 channels with non-specific antibody blockers or siRNA has been shown to decreases cancer growth and migration. Unfortunately, the non-specific nature of known inhibitors results in serious off-target effects, e.g., cardiovascular, digestive, musculoskeletal. In some embodiments, this disclosure relates to advancements demonstrating the PAS domain of EAG channels are useful for the treatment of diseases and mutations resulting in, and related to, an increase in potassium ion channel activity while obviating off-target effects.

[0007] In some embodiments, the disclosure is directed to a method of inhibiting an increase in potassium channel activity in a subject in need thereof, comprising administering an effective amount of a small molecule inhibitor that selectively binds to a Per-Amt-Sim (PAS) domain of Ether-a-go-go 1 (EAG1) potassium channels to a subject having a disorder associated with increased potassium channel activity; wherein the small molecule inhibitor comprises a polycyclic compound wherein at least one of the rings is unsaturated and at least one of the rings has a pendent substituent.

[0008] In some embodiments, a small molecule inhibitor may be a compound represented by Formula (I):R2(I).

[0009] L1may be a bond to L1A, -SOniiL1A-, -SOv11NR11L1A-, -NHC(O)NR11L1A-, - NRnL1A-, -C(O)L1A-, -C(O)OL1A-, -C(O)NR11L1A-, -OL1A-. -NRnSO2L1A-, NR11C(O)L1A-, -NRnC(O)OL1A-, NRnOL1A, -SL1A-, -substituted alkyl-L1A-, -unsubstituted alkyl-L1A-, -substituted heteroalkyl-L1A-, -unsubstituted heteroalkyl-L1A-, -substituted alkylene-L1A-, -unsubstituted alkylene-L1A-, -substituted heteroalkylene-L1A- -unsubstituted heteroalkylene-L1A-, -substituted cycloalkylene-L1A-, -unsubstituted cycloalkylene-L1A-, -substituted heterocycloalkylene-L1A-, -unsubstituted heterocycloalkylene-L1A-, -unsubstituted arylenein-, -unsubstituted arylene-L1A-, -substituted heteroarylene-L1A-, or -unsubstituted heteroarylene-L1A-.

[0010] R1may be independently absent, hydrogen, halogen, -CX13, -CHXS, -CH2X1, -OCX13, -OCHX12-OCH2X1, -0CH3, -OCH2R1A-N3, -CN, -SOn1R1D, SOv1NR1AR1B, -NHC(O)NR1AR1B, -N(O)m1, -NR1AR1B, -C(O)R1C, -C(O)-OR1C, -C(O)NR1AR1B, -OR1D, -NR1ASO2R1D, -NR1AC(O)R1C, -NR1AC( O)OR1C, -NR1AOR1C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0011] R2may be independently absent, hydrogen, halogen, -CX23, -CHX22, -CH2X2, -OCX3, -OCHX2, -OCH2X2, -OCH3, -OCH2R2A, -N3, -CN, -SOn2R1D, SOv2NR2AR2B, -NHC(O)NR2AR2B, -N(O)m2, -NR2AR2B, -C(O)R2C, -C(O)-OR2C. -C(O)NR2AR2B, -OR2D, -NR2ASO2R2D, -NR2AC(O)R2C, -NR2AC( O)OR2C, -NR2AOR2C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0012] R3may be independently absent, hydrogen, halogen. -CX33, -CHX32, -CH2X3, -OCX33, -OCHX32, -OCH2X3, -OCH3, -OCH2R3A, -N3, -CN, -SOn3R3D, SOv3NR3AR3B, -NHC(O)NR3AR3B, -N(O)m3, -NR3AR3B, -C(O)R3C, -C(O)-OR3C, -C(O)NR3AR3B, -OR3D, -NR3ASO2R3D, -NR3AC(O)R3C, -NR3AC( O)OR3C, -NR3AOR3C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0013] R4may be independently hydrogen, halogen, -CX43, -CHX42, -CH2X4, -OCX43, -OCHX42,-OCH2X4, -OCH3, -OCH2R4A, -N3, -CN, -SOn4R4D, SOv4NR4AR4B, -NHC(O)NR4AR4B, -N(O)m4, -NR4AR4B, -C(O)R4C, -C(O)-OR4C. -C(O)NR4AR4B, -OR4D, -NR4ASO2R4D, -NR4AC(O)R4C, -NR4AC( O)OR4C, -NR4AOR4C. substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0014] R5may be independently hydrogen, halogen, -CX53, -CHX52, -CH2X5, -OCX53, -OCHX52,-OCH2X5, -OCH3, -OCH2R5A, -N3, -CN, -SOn5R5D, SOv5NR5AR5B, -NHC(O)NR5AR5B, -N(O)m5, -NR5AR5B, -C(O)R5C, -C(O)-OR5C, -C(O)NR5AR5B, -OR5D, -NR5ASO2R5D, -NR5AC(O)R5C, -NR5AC( O)OR5C, -NR5AOR5C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0015] R6may be independently hydrogen, halogen, -CX63, -CHX62, -CH2X6, -OCX63, -OCHX62,-OCH2X6, -0CH3, -OCH2R6A, -N3, -CN, -SOn6R6D, SOv6NR6AR6B, -NHC(O)NR6AR6B, -N(O)m6, -NR6AR6B, -C(O)R6C, -C(O)-OR6C. -C(O)NR6AR6B, -OR6D, -NR6ASO2R6D, -NR6AC(O)R6C, -NR6AC( O)OR6C, -NR6AOR6C. substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0016] R7may be independently hydrogen, halogen. -CX73, -CHX72, -CH2X7, -OCX73, -OCHX72. -OCH2X7, -OCH3, -OCH2R7A, -N3, -CN, -SOn7R7D, SOv7NR7AR7B, -NHC(O)NR7AR7B, -N(O)m7, -NR7AR7B, -C(O)R7C, -C(O)-OR7C, -C(O)NR7AR7B, -OR7D, -NR7ASO2R7D, -NR7AC(O)R7C, -NR7AC( O)OR7C, -NR7AOR7C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0017] R8may be independently hydrogen, halogen, -CX83, -CHX82, -CH2X8, -OCX83, -OCHX82,-OCH2X8, -OCH3, -OCH2R8A, -N3, -CN, -SOn8R8D, SOv8NR8AR8B, -NHC(O)NR8AR8B, -N(O)m8, -NR8AR8B, -C(O)R8C, -C(O)-OR8C. -C(O)NR8AR8B, -OR8D, -NR8ASO2R8D, -NR8AC(O)R8C, -NR8AC( O)OR8C, -NR8AOR8C. substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0018] R9may be independently absent, hydrogen, halogen, -CX93, -CHX92, -CH2X9, -OCX93, -OCHX92, -OCH2X9, -OCH3, -OCH2R9A, -N3, -CN, -SOn9R9D, SOv9NR9AR9B, -NHC(O)NR9AR9B, -N(O)m9, -NR9AR9B, -C(O)R9C, -C(O)-OR9C, -C(O)NR9AR9B, -OR9D, -NR9ASO2R9D, -NR9AC(O)R9C, -NR9AC(O)OR9C, -NR9AOR9C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0019] R10may be independently absent, hydrogen, halogen, -CX103, -CHX102, -CH2X10, -OCX103, -OCHX102,-OCH2X10, -OCH3, -OCH2R10A, -N3, -CN, -SOn10R10D, SOv10NR10AR10B, -NHC(O)NR10AR10B, -N(O)m10, -NR10AR10B, -C(O)R10C, -C(O)-OR10C, -C(O)NR10AR10B, -OR10D, -NR10ASO2R10D, -NR10AC(O)R10C, -NR10AC(O)OR10C, -NR10AOR10C. substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0020] R12may be substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0021] In some embodiments, R1A, R1B, R1C, R1D, R2A, R2B, R2C, R2D, R3A, R3B, R3C, R3D, R4A, R4B, R4C, R4D, R5A, R5B, R5C, R5D, R6A, R6B, R6C, R6D, R7A, R7B, R7C, R7D, R8A, R8B, R8C, R8D, R9A, R9B, R9C, R9D, R10A, R10BR10C, R10D, R11and R12may be independently hydrogen, halogen, -CX3, -CHX2, -CH2X, -COOH, -CONH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0022] In some embodiments, Y1may be independently -C(R1)=, -C(L1A)=, or -N=; Y2may be independently -C(R2)=, -C(L1A)=, or -N=; Y3may be independently -C(R3)=, -C(L1A)=, or -N=; Y9may be independently -C(R9)=, -C(L1A)=, or -N=; Y10may be independently -C(R10)=, -C(L1A)=, or -N=.

[0023] L1Amay be a bond; n1, n2, n3, n4, n5, n6, n7, n8, n9, n10and n11may be independently an integer from 0 to 4; ml, m2, m3, m4, m5, m6, m7, m8, m9, mlO, vl, v2, v3, v4, v5, v6, v7, v8, v9, vlO, and vll may be independently an integer from 1 to 2; and / or X, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10may be independently-F, -Cl, -Br, or-I.

[0024] In some embodiments, a small molecule inhibitor may be a compound represented by Formula (II):(II). L1, L1A, R4, and R5may be as described herein.

[0025] R1may be independently hydrogen, halogen. -CX13, -CHX12, -CH2X1, -OCX13, -OCHX12-OCH2X1, -OCH3, -OCH2R1A, -N3, -CN, -SOn1R1D, SOv1NR1AR1B, -NHC(O)NR1AR1B, -N(O)m1, -NR1AR1B, -C(O)R1C, -C(O)-OR1C, -C(O)NR1AR1B, -OR1D, -NR1ASO2R1D, -NR1AC(O)R1C, -NR1AC( O)OR1C, -NR1AOR1C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0026] R2may be independently hydrogen, halogen, -CX23, -CHX2, -CH2X, -OCX3, -OCHX2,-OCH2X2, -OCH3, -OCH2R2A, -N3, -CN, -SOn2R1D, SOv2NR2AR2B, -NHC(O)NR2AR2B, -N(O)m2, -NR2AR2B, -C(O)R2C, -C(O)-OR2C, -C(O)NR2AR2B, -OR2D, -NR2ASO2R2D, -NR2AC(O)R2C, -NR2AC( O)OR2C, -NR2AOR2C. substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

[0027] R3may be independently hydrogen, halogen, -CX33, -CHX32, -CH2X3, -OCX33, -OCHX32,-OCH2X3, -OCH3, -OCH2R3A, -N3, -CN. -SOn3R3D, SOv3NR3AR3B, -NHC(O)NR3AR3B, -N(O)m3, -NR3AR3B, -C(O)R3C, -C(O)-OR3C, -C(O)NR3AR3B, -OR3D, -NR3ASO2R3D, -NR3AC(O)R3C, -NR3AC( O)OR3C, -NR3AOR3C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0028] R6may be independently absent, hydrogen, halogen, -CX63, -CHX62, -CH2X6, -OCX63, -OCHX62, -OCH2X6, -0CH3, -OCH2R6A, -N3, -CN, -SOn6R6D, SOv6NR6AR6B, -NHC(O)NR6AR6B, -N(O)m6, -NR6AR6B, -C(O)R6C, -C(O)-OR6C, -C(O)NR6AR6B, -OR6D, -NR6ASO2R6D, -NR6AC(O)R6C, -NR6AC(O)OR6C, -NR6AOR6C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0029] R7may be independently absent, hydrogen, halogen, -CX73, -CHX72, -CH2X7, -OCX73, -OCHX72, -OCH2X7, -0CH3, -OCH2R7A, -N3, -CN, -SOn7R7D, SOv7NR7AR7B, -NHC(O)NR7AR7B, -N(O)m7, -NR7AR7B, -C(O)R7C, -C(O)-OR7C. -C(O)NR7AR7B, -OR7D, -NR7ASO2R7D, -NR7AC(O)R7C, -NR7AC( O)OR7C, -NR7AOR7C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0030] R8may be independently absent, hydrogen, halogen, -CX83, -CHX82, -CH2X8, -OCX83, -OCHX82, -OCH2X8, -OCH3, -OCH2R8A, -N3, -CN, -SOn8R8D, SOv8NR8AR8B, -NHC(O)NR8AR8B, -N(O)m3, -NR8AR8B, -C(O)R8C, -C(O)-OR8C, -C(O)NR8AR8B, -OR8D, -NR8ASO2R8D, -NR8AC(O)R8C, -NR8AC( O)OR8C, -NR8AOR8C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0031] R9may be independently absent, hydrogen, halogen, -CX93, -CHX92, -CH2X9, -OCX93, -OCHX92, -OCH2X9, -OCH3, -OCH2R9A, -N3, -CN, -SOn9R9D, SOv9NR9AR9B, -NHC(O)NR9AR9B, -N(O)m9, -NR9AR9B, -C(O)R9C, -C(O)-OR9C. -C(O)NR9AR9B, -OR9D, -NR9ASO2R9D, -NR9AC(O)R9C, -NR9AC( O)OR9C, -NR9AOR9C. substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0032] R10may be independently absent, hydrogen, halogen, -CX103, -CHX102, -CH2X10, -OCX103, -OCHX102, -OCH2X10, -OCH3, -OCH2R10A, -N3, -CN, -SOn10R10D, SOv10NR10AR10B. -NHC(O)NR10AR10B, -N(O)m10, -NR10AR10B, -C(O)R10C, -C(O)-OR10C, -C(O)NR10AR10B, -OR10D, -NR10ASO2R10D, -NR10AC(O)R10C, -NR10AC(O)OR10C, -NR10AOR10C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0033] R12may be independently absent, hydrogen, halogen, -CX123, -CHX122, -CH2X12, -OCX123, -OCHX122,-OCH2X12, -OCH3, -OCH2R12A, -N3, -CN, -SOn12R12D, SOv12NR12AR12B,-NHC(O)NR12AR12B. -N(O)m12, -NR12AR12B, -C(O)R12C, -C(O)-OR12C, -C(O)NR12AR12B. -OR12D, -NR12ASO2R12D-NR12AC(O)R12C, -NR12AC( O)OR12C, -NR12AOR12C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0034] R1A, R1B, R1C, R1D, R2A, R2B, R2C, R3A, R3B, R3C, R6D, R7A, R7B, R7C, R7D, R8A, R8B, R8C, R8D, R9A, R9B, R9C, R9D, R10A, R10B, R10C, R10D, and R12A, R12BR12C, R12Dmay be independently hydrogen, -CX3, -CHX2, -CH2X, -COOH, -CONH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0035] Y6may be independently -C(R6)=, -C(L1A)=, -C(R6)H-, -C(L1A)H-, -(R6)C(L1A)-, -(OH)C(R6)-, -(OH)C(L1A)-, -O-, -S-, -N=, -N(R6)-, -N(L1A)-, -SO2-; Y7may be independently -C(R7)=,-C(L1A)=, -C(R7)H-, -C(L1A)H-, -(R7)C(L1A)-, -(OH)C(R7)-, -(OH)C(L1A)-, -O-, -S-, -N=, -N(R7)-. -N(L1A)-, -SO2-; Y8may be independently -C(R8)= -C(L1A)= -C(R8)H-, -C(L1A)H-, -(R8)C(L1A)-, -(OH)C(R8)-, -(OH)C(L1A)-, -O-, -S-, -N= -N(R8)-, -N(L1A)-, -SO2-; Y9may be independently -C(R9)=,-C(L1A)=, -C(R9)H-, -C(L1A)H-, -(R9)C(L1A)-, -(OH)C(R9)-, -(OH)C(L1A)-, -O-, -S-, -N=, -N(R9)-, -N(L1A)-, -SO2-; Y10may be independently -C(R10)=,-C(L1A)=, -C(R10)H-, -C(L1A)H-, -(R10)C(L1A)-, -(OH)C(L1A)-, -(OH)C(L1A)-, -O-, -S-, -N=. -N(R10)-, -N(L1A)-, -SO2-; Y12may be independently -C(R12)=. -C(L1A)=, -C(R12)H-. -C(L1A)H-, -(R12)C(L1A)-, -(OH)C(R12)-, -(OH)C(L1A)-, -O-, -S-, -N=, -N(R12)-, -N(L1A)-, -SO2-.

[0036] n1, n2, n3, n6, n7, n8, n9, n10, and n12may be independently an integer from 0 to 4 j m1, m2, m3, m6, m7, m8, m9, m10, m12, v1, v2, v3, v6, v7, v8, v9, v10and v12may be independently an integer from 1 to 2; and X1, X2, X3, X6, X7, X8, X9, X10, and X12may be independently-F, -Cl, -Br, or-I.

[0037] In some embodiments, a small molecule inhibitor may be a compound represented by Formula (III):(III). L1, L1A, R1, R2, R3, R4, R5, R6, R7, and R8may be as described herein.

[0038] L2may be a bond, -SOn12L2A-, -SOv12NR12L2A-, -NHC(O)NR12L2A-, -NR12L2A-, -C(O)L2A-, -C(O)OL2A-, -C(O)NR12L2A-, -OL2A-. -NR12SO2L2A-, NR12C(O)L2A-, -NR12C(O)OL2A-, NR12OL2A-SL2A-, -substituted alkyl-L1A-, -unsubstituted alkyl-L1A-, -substituted heteroalkyl-L1A-, -unsubstituted heteroalkyl-L1A-, -substituted alkylene-L1A-, -unsubstituted alkylene-L1A-, -substituted heteroalkylene-L1A-, -unsubstituted heteroalkylene-L1A-, -substituted cycloalkylene-L1A-, -unsubstituted cycloalkylene-L1A-, -substituted heterocycloalkylene-L1A-, -unsubstituted heterocycloalkylene-L1A-, -unsubstituted arylene-L1A-, -unsubstituted arylene-L1A-, -substituted heteroarylene-L1A-, or -unsubstituted heteroarylene-L1A-.

[0039] L2Amay be a bond, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene; n12may be an integer from 0 to 4; and / or v12may be an integer from 1 to 2.

[0040] An alteration in potassium ion channel activity' can potentially disrupt signaling pathways in diseased cells, e.g., including but not limited to cell proliferation, migration, invasion and resistance to apoptosis. In some embodiments, the alteration is an increase in potassium channel activity. In some embodiments, and without limiting the disclosure, the diseased cells may be due to cancer, genetic disorders, and / or neurological disorders. In some embodiments, the disclosure is directed to a method for treating such disease states comprising administering to a patient having cancer and / or genetic disorder and / or neurological disorder a therapeutically effective amount of a compound of Formula I -III, or a pharmaceutically acceptable salt thereof, alone or in combination with a pharmaceutically acceptable carrier, excipient and / or diluents. As will be appreciated by those of ordinary skillin the art, this disclosure relates to other disease states not listed which may be associated with an alteration in potassium channel activity.

[0041] In some embodiments, this disclosure relates to a pharmaceutical composition used to deliver a described small molecule inhibitor in a safe and effective way. In some embodiments, the disclosure is directed to a pharmaceutical composition comprising a therapeutically effective amount of a small molecule inhibitor of any of Formula I -III, and a pharmaceutically acceptable carrier, excipient and / or diluents.

[0042] In some embodiments, the pharmaceutical composition may be formulated. For example, the pharmaceutical composition may be an oral sterile formulation, an oral non-sterile formulation, an inhalation formulation, a parenteral formulation, a sublingual formulation, atopical formulation, atransdermal formulation, a nasal formulation, an ocular formulation, an otic formulation, a rectal formulation, a vaginal formulation, and / or any combination thereof.

[0043] In some embodiments, the pharmaceutical composition may be in a unit dose form. For example, the unit dose form may be a solution, a cream, a dry powder inhaler, a capsule, a pill, a gel, a lozenge, a chewable tablet, and / or an effervescent tablet.

[0044] Without wishing to be bound by any particular theory, there can be discussion herein of beliefs or understandings of underlying principles relating to the invention. It is recognized that regardless of the ultimate correctness of any mechanistic explanation or hypothesis, an embodiment of the invention can nonetheless be operative and useful.BRIEF DESCRIPTION OF THE DRAWINGS

[0045] FIGS. 1 provides a graph plotting surface plasmon resonance (SPR) response versus time for example small molecule inhibitor compound C38 binding to the isolated Per-Amt-Sim (PAS) domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0046] FIG. 2 provides a graph plotting surface plasmon resonance (SPR) response versus concentration for example small molecule inhibitor compound C38 binding to the isolated Per-Amt-Sim (PAS) domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0047] FIG. 3 provides a graph plotting surface plasmon resonance (SPR) response versus time for example small molecule inhibitor compound C43 binding to the isolated Per- Amt-Sim (PAS) domain located at the N-terminus of the Ether- a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0048] FIG. 4 provides a graph plotting surface plasmon resonance (SPR) response versus concentration for example small molecule inhibitor compound C43 binding to the isolated Per-Amt-Sim (PAS) domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0049] FIG. 5 provides a graph plotting surface plasmon resonance (SPR) response versus time for example small molecule inhibitor compound C12 binding to the isolated Per-Amt-Sim (PAS) domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0050] FIG. 6 provides a graph plotting surface plasmon resonance (SPR) response versus concentration for example small molecule inhibitor compound C12 binding to the Per-Amt-Sim (PAS) domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0051] FIG. 7 provides a graph plotting surface plasmon resonance (SPR) response versus time for example small molecule inhibitor compound Cl 1 binding to the isolated Per-Amt-Sim (PAS) domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0052] FIG. 8 provides a graph plotting surface plasmon resonance (SPR) response versus concentration for example small molecule inhibitor compound Cl 1 binding to the isolated Per-Amt-Sim (PAS) domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0053] FIG. 9 provides a graph plotting surface plasmon resonance (SPR) response versus time for example small molecule inhibitor compound EN1378 binding to the isolated Per-Amt-Sim (PAS) domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0054] FIG. 10 provides a graph plotting surface plasmon resonance (SPR) response versus concentration for example small molecule inhibitor compound EN1378 binding to the isolated Per-Amt-Sim (PAS) domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0055] FIG. 11 provides a diverging bar chart plotting current inhibition (%) from two-electrode voltage-clamp (TEVC) currents of EAG1 channels expressed in Xenopus laevis(frog) oocytes in response to example small molecule inhibitor compounds administered at a concentration of 100 pM in accordance with embodiments of the present disclosure.

[0056] FIG. 12 provides a graph plotting current inhibition (%) versus concentration of example small molecule inhibitor compound C38 in wild type (WT) and mutant (APAS) channels with the deletion of the Per-Amt-Sim (PAS) domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0057] FIG. 13 provides a graph plotting current inhibition (%) versus concentration of example small molecule inhibitor compound C43 in wild type (WT) and mutant (APAS) channels in accordance with embodiments of the present disclosure.

[0058] FIG. 14 provides a graph plotting current inhibition (%) versus concentration of example small molecule inhibitor compound EN1387 in wild type (WT) and mutant (APAS) channels in accordance with embodiments of the present disclosure.

[0059] FIG. 15 provides a graph plotting current inhibition (%) versus concentration of example small molecule inhibitor compounds compared to commercially available inhibitors in wild type (WT) and mutant (APAS) channels in accordance with embodiments of the present disclosure.

[0060] FIG. 16 provides a ribbon diagram showing the docking position of example small molecule inhibitor compound C38 in the isolated Per-Amt-Sim (PAS) domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0061] FIG. 17 provides a surface representation diagram showing the docking position of example small molecule inhibitor compound C38 in the isolated Per-Amt-Sim (PAS) domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0062] FIG. 18 provides a ribbon diagram showing the docking position of example small molecule inhibitor compound C43 in the isolated Per-Amt-Sim (PAS) domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0063] FIG. 19 provides a surface representation diagram showing the docking position of example small molecule inhibitor compound C43 in the isolated Per-Amt-Sim (PAS) domainlocated at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0064] FIG. 20 provides a ribbon diagram showing the docking position of example small molecule inhibitor compound Cl 1 in the isolated Per-Amt-Sim (PAS) domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0065] FIG. 21 provides a ribbon diagram showing the docking position of example small molecule inhibitor compound C12 in the isolated Per-Amt-Sim (PAS) domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.

[0066] FIG. 22 provides a ribbon diagram showing the docking position of example small molecule inhibitor compound EN1378 in the isolated Per-Amt-Sim (PAS) domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein in accordance with embodiments of the present disclosure.DETAILED DESCRIPTIONDefinitions

[0067] In general the terms and phrases used herein have their art-recognized meaning, which can be found by reference to standard texts, journal references and contexts known to those skilled in the art. The following definitions are provided to clarify their specific use in the context of the invention.

[0068] Where substituent groups are specified by their conventional chemical formulae, written from left to right, they equally encompass the chemically identical substituents that would result from writing the structure from right to left, e.g., -CH2O- is equivalent to -OCH2-.

[0069] The term “alkyl,” by itself or as part of another substituent, means, unless otherwise stated, a straight (i.e., unbranched) or branched carbon chain (or carbon), or combination thereof, which may be fully saturated, mono- or polyunsaturated, having the number of carbon atoms designated (i.e., C1-C10 means one to ten carbons). Alkyl may be an uncyclized chain. Examples of saturated alkyl groups include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, homologs and isomers of, for example, n-pentyl, n-hexyl, n-hept l. n-octyl, and the like. An unsaturated alkyl group may be one having one or more double bonds or triple bonds. Examples of unsaturated alkylgroups include, but are not limited to, vinyl, 2-propenyl, croty l, 2-isopentenyl, 2-(butadienyl), 2,4-pentadienyl, 3-(l,4-pentadienyl). ethynyl, 1- and 3-propynyl, 3-butynyl, and the higher homologs and isomers. An alkoxy may be an alkyl attached to the remainder of the molecule via an oxygen linker (-O-).

[0070] The term “alkylene,” by itself or as part of another substituent, means, unless otherwise stated, a straight (i.e., unbranched) or branched carbon chain wherein there may be at least one carbon-carbon double bond, as exemplified, but not limited by, -CH2CH2CH2CH2-. Typically, an alkyl (or alkylene) group will have from 1 to 24 carbon atoms.

[0071] The term “heteroalkyl,” by itself or in combination with another term, means, unless otherwise stated, a straight or branched chain, or combinations thereof, including at least one carbon atom and at least one heteroatom (e.g., selected from the group consisting of O, N, P, Si, and S), and wherein the nitrogen and sulfur atoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized. The heteroatom(s) (e g., O, N, P, S, B, As, and Si) may be placed at any interior position of the heteroalkyl group or at the position at which the alkyl group is attached to the remainder of the molecule. Heteroalkyl may be an uncyclized chain. Examples include, but are not limited to: -CH2-CH2-S-CH3, -C(O)-O-CH2-CH3, -C(O)-CH2-NH-C(O)CH3, -O-CH3, -C(O)-NH-, -CH2-CH2-CH2-NH-CH3. Up to two or three heteroatoms may be consecutive, such as, for example, -N(CH3)-C(O)-CH2-CH2-O-.

[0072] Similarly, the term “heteroalkylene,” by itself or as part of another substituent, means, unless otherwise stated, a straight or branched chain, or combinations thereof, including at least one carbon-carbon double bond and at least one heteroatom, as exemplified, but not limited by, -CH2-CH=CH-O-CH2-CH2- and -CH=CH-CH2-NH-CH2-. For heteroalkylene groups, heteroatoms can also occupy either or both of the chain termini (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, and the like). Still further, for alkylene and heteroalkylene linking groups, no orientation of the linking group is implied by the direction in which the formula of the linking group is written. For example, the formula -C(O)2R'- represents both -C(O)2R'- and -R'C(O)2-. As described above, heteroalkyl groups, as used herein, include those groups that are attached to the remainder of the molecule through a heteroatom, such as -C(O)R', -C(O)NR', -NR'R", -OR', -SR', and / or -SO2R'. Where “heteroalkyl” is recited, followed by recitations of specific heteroalkyl groups, such as -NR'R" or the like, it will be understood that the terms heteroalkyl and -NR'R" are not redundant or mutually exclusive. Rather, the specific heteroalkyl groups are recited to addclarity. Thus, the term “heteroalkyl” should not be interpreted herein as excluding specific heteroalkyl groups, such as -NR'R" or the like.

[0073] The terms ‘“cycloalkyl” and “heterocycloalkyl,” by themselves or in combination with other terms, mean, unless otherwise stated, cyclic versions of “alkyl” and “heteroalkyl,” respectively. Cycloalkyl and heteroalkyl are not aromatic. Additionally, for heterocycloalkyl, a heteroatom can occupy the position at which the heterocycle may be attached to the remainder of the molecule. Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1 -cyclohexenyl, 3 -cyclohexenyl, cycloheptyl, and the like. Examples of heterocycloalkyl include, but are not limited to, 1-(1,2,5,6-tetrahydropyridyl), 1 -piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1 -piperazinyl, 2-piperazinyl, and the like.

[0074] Similarly, the terms “cycloalkylene” and a “heterocycloalkylene,” by themselves or in combination with other terms, mean, unless otherwise stated, cyclic versions of “alkylene” and “heteroalkylene,” respectively.

[0075] The terms “halo” or “halogen,” or “X” by themselves or as part of another substituent, mean, unless otherwise stated, a fluorine, chlorine, bromine, or iodine atom. Additionally, terms such as “haloalkyl” are meant to include monohaloalkyl and polyhaloalkyl. For example, the term “halo(Ci-C4)alkyl” includes, but is not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, and the like.

[0076] The term “acyl” means, unless otherwise stated, -C(O)R where R may be a substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

[0077] The term “aryl” means, unless otherwise stated, a polyunsaturated, aromatic, hydrocarbon substituent, which can be a single ring or multiple rings (for example from 1 to 3 rings) that are fused together (i.e., a fused ring aryl) or linked covalently. A fused ring aryl refers to multiple rings fused together wherein at least one of the fused rings is an aryl ring. The term “heteroaryl” refers to aryl groups (or rings) that contain at least one heteroatom such as N, O, or S, wherein the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen atom(s) are optionally quaternized. Thus, the term “heteroaryl” includes fused ring heteroaryl groups (i.e., multiple rings fused together wherein at least one of the fused rings is a heteroaromatic ring). A 5,6-fused ring heteroarylene refers to two rings fused together,wherein one ring has 5 members and the other ring has 6 members, and wherein at least one ring is a heteroaryl ring. Likewise, a 6,6-fused ring heteroarylene refers to two rings fused together, wherein one ring has 6 members and the other ring has 6 members, and wherein at least one ring is a heteroaryl ring. And a 6,5-fused ring heteroarylene refers to two rings fused together, wherein one ring has 6 members and the other ring has 5 members, and wherein at least one ring is a heteroaryl ring. A heteroaryl group can be attached to the remainder of the molecule through a carbon or heteroatom. Non-limiting examples of aryl and heteroaryl groups include phenyl, naphthyl, pyrrolyl, pyrazolyl, pyridazinyl, triazinyl, pyrimidinyl, imidazolyl, pyrazinyl, purinyl, oxazolyl, isoxazolyl, thiazolyl, furyl, thienyl, pyridyl, pyrimidyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, benzofuran, isobenzofuranyl, indolyl. isoindolyl, benzothiophenyl, isoquinolyl, quinoxalinyl, quinolyl, 1 -naphthyl, 2-naphthyl, 4-biphenyl, 1 -pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 2-imidazolyl, 4-imidazolyl, pyrazinyl, 2-oxazolyl, 4-oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-furyl, 3-furyl, 2 -thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5 -benzothiazolyl, purinyl, 2-benzimidazolyl, 5-indolyl, 1 -isoquinolyl, 5-isoquinolyl, 2-quinoxalinyl. 5-quinoxalinyl, 3-quinolyl, and 6-quinolyl. Example substituents for each of the above noted aryl and heteroaryl ring systems are described below.

[0078] A “fused ring aryl-heterocycloalkyl” is an aryl fused to a heterocycloalkyl. A “fused ring heteroaryl-heterocycloalky 1"’ is a heteroaryl fused to a heterocycloalkyl. A “fused ring heterocycloalky 1-cycloalkyl” is a heterocycloalkyl fused to a cycloalkyl. A “fused ring heterocycloalkyl-heterocycloalkyl” is a heterocycloalkyl fused to another heterocycloalkyl. Fused ring aryl-heterocycloalkyl, fused ring heteroaryl-heterocycloalkyl, fused ring heterocycloalkyl-cycloalkyl, or fused ring heterocycloalkyl-heterocycloalkyl may each independently be unsubstituted or substituted with one or more of the substituents described herein. Fused ring aryl-heterocycloalkyl, fused ring heteroaryl-heterocycloalkyl, fused ring heterocycloalkyl-cycloalkyl, or fused ring heterocycloalkyl-heterocycloalky 1 may each independently be named according to the size of each of the fused rings. Thus, for example, 6,5 aryl-heterocycloalkyl fused ring describes a 6 membered aryl moiety fused to a 5 membered heterocycloalkyl. Spirocyclic rings are two or more rings wherein adjacent rings are attached through a single atom. The individual rings within spirocyclic rings may be identical or different. Individual rings in spirocyclic rings may be substituted or unsubstituted and may have different substituents from other individual rings within a set of spirocyclic rings. Possible substituents for individual rings within spirocyclic rings are the possiblesubstituents for the same ring when not part of spirocyclic rings (e.g. substituents for cycloalkyl or heterocycloalkyl rings). Spirocyclic rings may be substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heterocycloalkylene and individual rings within a spirocyclic ring group may be any of the immediately previous list, including having all rings of one type (e.g. all rings being substituted heterocycloalkylene wherein each ring may be the same or different substituted heterocycloalkylene). When referring to a spirocyclic ring system, heterocyclic spirocyclic rings means a spirocyclic rings wherein at least one ring is a heterocyclic ring and wherein each ring may be a different ring. When referring to a spirocyclic ring system, substituted spirocyclic rings means that at least one ring may be substituted and each substituent may optionally be different.

[0079] Each of the above terms (e.g., '’alkyl.” “heteroalkyl, ” “cycloalkyl,” “heterocycloalkyl,” “aryl,” and “heteroaryl”) includes both substituted and unsubstituted forms of the indicated group. Example substituents for each type of group are described below.

[0080] Substituents for the alkyl and heteroalkyl groups (including those groups often referred to as alkylene, alkenyl, heteroalkylene, heteroalkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, and heterocycloalkenyl) can be one or more of a variety of groups selected from, but not limited to, -OR1, =0, =NR’, =N-0R', -NR'R", -SR', -halogen, -SiR'R'R'", -OC(O)R', -C(O)R', -CO2R', -CONR'R", -0C(0)NR'R", -NR" C(0)R', -NR'-C(0)NR" R"', -NR" C(O)2R', -NR-C(NR'R" R'")=NR"", -NR-C(NR'R")=NR'", -S(O)R', -S(O)2R', -S(O)2NR'R", -NRSO2R', -NR'NR" R"', -ONR'R", -NR'C=(O)NR" NR," R"", -CN, -NO2, -NR'SChR", -NR'C=(0)R", -NR'C(O)-OR", or -NR'OR". R, R', R", R'", and R"" each preferably independently refer to hydrogen, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkyl, alkoxy, or thioalkoxy groups, or arylalkyl groups. When a compound of the disclosure includes more than one R group, for example, each of the R groups may be independently selected as are each R', R", R'", and R"" group when more than one of these groups is present. When R' and R" are attached to the same nitrogen atom, they can be combined with the nitrogen atom to form a 4-, 5-, 6-, or 7-membered ring. For example, -NR'R" includes, but is not limited to, 1 -pyrrolidinyl and 4-morpholinyl. From the above discussion of substituents, one of skill in the art will understand that the term “alkyl” is meant to include groups including carbon atoms bound to groups other than hydrogen groups, suchas haloalkyl (e.g., -CF3and -CH2CF3) and acyl (e.g., -C(O)CH3, -C(O)CF3, -C(O)CH2OCH3, and the like).

[0081] Substituents for rings (e.g. cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylene, heterocycloalkylene, arylene, or heteroarylene) may be depicted as substituents on the ring rather than on a specific atom of a ring (commonly referred to as a floating substituent). In such a case, the substituent may be attached to any of the ring atoms (obeying the rules of chemical valency) and in the case of fused rings or spirocyclic rings, a substituent depicted as associated with one member of the fused rings or spirocyclic rings (a floating substituent on a single ring), may be a substituent on any of the fused rings or spirocyclic rings (a floating substituent on multiple rings). When a substituent is attached to a ring, but not a specific atom (a floating substituent), and a subscript for the substituent is an integer greater than one, the multiple substituents may be on the same atom, same ring, different atoms, different fused rings, different spirocyclic rings, and each substituent may optionally be different. Where a point of attachment of a ring to the remainder of a molecule is not limited to a single atom (a floating substituent), the attachment point may be any atom of the ring and in the case of a fused ring or spirocyclic ring, any atom of any of the fused rings or spirocyclic rings while obeying the rules of chemical valency. Where a ring, fused rings, or spirocyclic rings contain one or more ring heteroatoms and the ring, fused rings, or spirocyclic rings are shown with one more floating substituents (including, but not limited to, points of attachment to the remainder of the molecule), the floating substituents may be bonded to the heteroatoms. Where the ring heteroatoms are shown bound to one or more hydrogens (e.g. a ring nitrogen with two bonds to ring atoms and a third bond to a hydrogen) in the structure or formula with the floating substituent, when the heteroatom is bonded to the floating substituent, the substituent will be understood to replace the hydrogen, while obeying the rules of chemical valency.

[0082] Two or more substituents may optionally be joined to form aryl, heteroaryl, cycloalkyl, or heterocycloalkyl groups. Such so-called ring-forming substituents are typically, though not necessarily, found attached to a cyclic base structure. In one embodiment, the ring-forming substituents are attached to adjacent members of the base structure. For example, two ring-forming substituents attached to adjacent members of a cyclic base structure create a fused ring structure. In another embodiment, the ring-forming substituents are attached to a single member of the base structure. For example, two ring-forming substituents attached to a single member of a cyclic base structure create a spirocyclicstructure. In yet another embodiment, the ring-forming substituents are attached to nonadjacent members of the base structure.

[0083] As used herein, the terms “heteroatom” or “ring heteroatom” are meant to include oxygen (O), nitrogen (N), sulfur (S), phosphorus (P), Boron (B), Arsenic (As), and silicon (Si).

[0084] In some embodiments, a “substituent group,” as used herein, means a group selected from the following moieties: halogen, -CF3, -CCl₃,-CBr3, -CI3, -CHF2, -CHCh,-CHBr₂, -CHI2. -CH2F -CH2CI, -CH2Br. -CH2I. -CN, -OH, -NH2, -COOH. -CONH2. -NO2, -SH, -SCH3, -SO3H, -SO4H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, OCFs, OCCh, OCBr3, OCI3, OCHF2, OCHCh, -OCHB12. -OCHI2, -OCH2F, -OCH2CI, -OCH2Br, -OCH2I, unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl. unsubstituted aryl, and / or unsubstituted heteroaryl.

[0085] In some embodiments, a “substituent group,” as used herein, means a group selected from alkyl, heteroalkyl, cycloalkyl. heterocycloalkyl, aryl, and heteroaryl, substituted with at least one substituent selected from: halogen, -CF3, -CCl₃,-CBr3, -CI3, -CHF2, -CHCh -CHBr2,-CHI2, -CH2F -CH₂Cl, -CH₂Br, - CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SCHy -SO3H, -SO4H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2, -NHC(O)NH2, -NHSO2H, -NHC(O)H, -NHC(O)OH, -NHOH, -OCF3, -OCCh, -OCBr3, -OCI3, -OCHF2, -OCHCh. -OCHBr2, -OCHI2.-OCH2F. -OCH2CI, -OCH2Br, -OCH2I. unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, and / or unsubstituted heteroaryl.

[0086] In some embodiments, a “substituent group,” as used herein, means a group selected from alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, substituted with at least one alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, substituted with at least one substituent selected from: halogen, -CF3, -CCl₃, -CB, -Ch, -CHF2, -CHCh,-CHBr2,-CHI2, -CH2F -CH2CI, -CH2Br. - CH2I, -CN, -OH, -NH2, -COOH, -CONH2, -NO2, -SH, -SCH3, -SO3H, -SO4H, -SO2NH2, -NHNH2, -ONH2, -NHC(O)NHNH2. -NHC(O)NH2. -NHSO2H. -NHC(O)H, -NHC(O)OH, -NHOH, -OCF3, -OCCh, -OCBrs, -OCI3, -OCHF2, -OCHCh, -OCHBr2, -OCHI2, OCH2F, OCH2CI, OCH2Br, -OCH2I, unsubstituted alkyl, unsubstitutedheteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, and / or unsubstituted heteroaryl.

[0087] In some embodiments, each substituted group described in the compounds herein may be substituted with at least one substituent group. More specifically, in some embodiments, each substituted alkyl, substituted heteroalkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted alkylene, substituted heteroalkylene, substituted cycloalkylene, substituted heterocycloalkylene, substituted arylene, and / or substituted heteroarylene described in the compounds herein are substituted with at least one substituent group.

[0088] In some embodiments of the compounds herein, each substituted or unsubstituted alkyl may be a substituted or unsubstituted C 1-C20 alkyl, each substituted or unsubstituted heteroalkyl may be a substituted or unsubstituted 2 to 20 membered heteroalkyl, each substituted or unsubstituted cycloalkyl may be a substituted or unsubstituted C3-C8 cycloalkyl, each substituted or unsubstituted heterocycloalkyl may be a substituted or unsubstituted 3 to 8 membered heterocycloalkyl, each substituted or unsubstituted aryl may be a substituted or unsubstituted C6-C10 aryl, and / or each substituted or unsubstituted heteroaryl may be a substituted or unsubstituted 5 to 10 membered heteroaryl. In embodiments herein, each substituted or unsubstituted alkylene may be a substituted or unsubstituted C1-C20 alkydene, each substituted or unsubstituted heteroalkylene may be a substituted or unsubstituted 2 to 20 membered heteroalkylene, each substituted or unsubstituted cycloalkydene may be a substituted or unsubstituted C3-C8 cycloalkylene, each substituted or unsubstituted heterocycloalkylene may be a substituted or unsubstituted 3 to 8 membered heterocycloalkylene, each substituted or unsubstituted arylene may be a substituted or unsubstituted C6-C10 arylene, and / or each substituted or unsubstituted heteroarylene may be a substituted or unsubstituted 5 to 10 membered heteroarylene.

[0089] Certain compounds of the present invention may possess asymmetric carbon atoms (optical or chiral centers) or double bonds; the enantiomers, racemates, diastereomers, tautomers, geometric isomers, stereoisometric forms that may be defined, in terms of absolute stereochemistry, as (R)-or (S)- or, as (D)- or (L)- for amino acids, and individual isomers are encompassed within the scope of the present invention. The compounds of the present invention do not include those that are known in art to be too unstable to synthesize and / or isolate. The present invention may include compounds in racemic and optically pure forms. Optically active (R)- and (S)-, or (D)- and (L)-isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. When the compounds describedherein contain olefinic bonds or other centers of geometric asymmetry, and unless specified otherwise, compounds may include both E and Z geometric isomers.

[0090] As used herein, the term "‘isomers” refers to compounds having the same number and kind of atoms, and hence the same molecular weight, but differing in respect to the structural arrangement or configuration of the atoms.

[0091] The term “tautomer,” as used herein, refers to one of two or more structural isomers which exist in equilibrium, and which are readily converted from one isomeric form to another.

[0092] It will be apparent to one skilled in the art that certain compounds of this invention may exist in tautomeric forms, all such tautomeric forms of the compounds being within the scope of the invention.

[0093] Unless otherwise stated, structures depicted herein are also meant to include all stereochemical forms of the structure; i.e., the (R) and (S) configurations for each asymmetric center. Therefore, single stereochemical isomers as well as enantiomeric and diastereomeric mixtures of the present compounds, generally recognized as stable by those skilled in the art, are within the scope of the invention.

[0094] Unless otherwise stated, structures depicted herein are also meant to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, replacement of fluoride by18F, or the replacement of a carbon by13C- or14C-enriched carbon are within the scope of this invention.

[0095] The compounds of the present invention may also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the compounds may be radiolabeled with radioactive isotopes, such as for example tritium (3H), iodine-125 (125I), or carbon-14 (14C). All isotopic variations of the compounds of the present invention, whether radioactive or not, are encompassed within the scope of the present invention.

[0096] It should be noted that throughout the application that alternatives are written in Markush groups, for example, wherein a ring substituent has more than one possible attachment point. It is specifically contemplated that each member of the Markush group should be considered separately, thereby comprising another embodiment, and the Markush group is not to be read as a single unit.

[0097] “Analog,’' or “analogue” is used in accordance with its plain ordinary meaning within Chemistry and Biology and refers to a chemical compound that may be structurally similar to another compound (i.e., a so-called “reference” compound) but differs in composition, e.g., in the replacement of one atom by an atom of a different element, or in the presence of a particular functional group, or the replacement of one functional group by another functional group, or the absolute stereochemistry of one or more chiral centers of the reference compound. Accordingly, an analog may be a similar compound or a compound comparable in function and appearance but not in structure or origin to a reference compound.

[0098] The terms "a" or "an," as used herein means one or more. In addition, the phrase "substituted with a[n]," as used herein, means the specified group may be substituted with one or more of any or all of the named substituents. For example, where a group, such as an alkyl or heteroaryl group, is "substituted with an unsubstituted C1-C20 alkyl, or unsubstituted 2 to 20 membered heteroalkyl," the group may contain one or more unsubstituted C1-C20 alkyls, and / or one or more unsubstituted 2 to 20 membered heteroalkyls.

[0099] The symbol “ / V’” denotes the point of attachment of a chemical moiety to the remainder of a molecule or chemical formula.

[0100] Where a moiety is substituted with an R substituent, the group may be referred to as “R-substituted.” Where a moiety is R-substituted, the moiety may be substituted with at least one R substituent and each R substituent may be optionally different. Where a particular R group is present in the description of a chemical genus (such as Formula (I)), a Roman decimal symbol may be used to distinguish each appearance of that particular R group. For example, where multiple R12substituents are present, each R12substituent may be distinguished as R12A, R12B, R12C, etc., wherein each of R12A, R12B, R12C, etc. is defined within the scope of the definition of R12and optionally differently.

[0101] Description of compounds of the present invention may be limited by principles of chemical bonding known to those skilled in the art. Accordingly, where a group may be substituted by one or more of a number of substituents, such substitutions are selected so as to comply with principles of chemical bonding and to give compounds which are not inherently unstable and / or would be known to one of ordinary skill in the art as likely to be unstable under ambient conditions, such as aqueous, neutral, and several known physiological conditions. For example, a heterocycloalkyl or heteroaryl is attached to the remainder of the molecule via a ring heteroatom in compliance with principles of chemical bonding known to those skilled in the art thereby avoiding inherently unstable compounds.

[0102] As used herein, “EAG” or “EAG1” refers to ether-a-go-go-1, which is a voltage-gated potassium channel.

[0103] As used herein, “PAS” or “PAS domain” or “PAS domain of EAG1” refers to the Per-Amt-Sim domain located at the N-terminus of the Ether-a-go-go (EAG1) potassium channel protein.

[0104] As defined herein, the term “inhibition”, “inhibit”, “inhibiting” and the like in reference to a protein-inhibitor interaction means negatively affecting (e.g. decreasing) the activity or function of the protein relative to the activity or function of the protein in the absence of the inhibitor. In embodiments inhibition means negatively affecting (e.g. decreasing) the activity of the protein relative to the activity levels in the absence of the inhibitor. In embodiments inhibition refers to reduction of a disease or symptoms of disease. In embodiments, inhibition refers to a reduction in the activity of a particular protein target. Thus, inhibition includes, at least in part, partially or totally blocking stimulation, decreasing, preventing, or delaying activation, or inactivating, desensitizing, or down-regulating signal transduction or enzymatic activity of a protein. In embodiments, inhibition refers to a reduction of activity of a target protein resulting from a direct interaction (e.g. an inhibitor binds to the target protein). In embodiments, inhibition refers to a reduction of activity of a target protein from an indirect interaction (e.g. an inhibitor binds to a protein that activates the target protein, thereby preventing target protein activation).

[0105] In some embodiments, the term “inhibition”, “inhibit”, “inhibiting” and the like means negatively affecting (e.g. decreasing or suppressing) the expression of the protein relative to the expression level of the protein in the absence of the inhibitor. In embodiments inhibition means negatively affecting (e.g. decreasing or suppressing) activity of the protein as compared to the absence of the inhibitor.

[0106] The term "small molecule " or the like as used herein refers, unless indicated otherwise, to a molecule having a molecular weight in the range of about 100 to about 1000 Dalton. For example, the molecular weight of the small molecule may be about 100, about 101, about 102, about 103, about 104, about 105, about 106, about 107, about 108, about 109, about 110, about 110 to about 120. about 120 to about 130, about 130 to about 140. about 140 to about 150, about 150 to about 160, about 160 to about 170, about 170 to about 180, about 180 to about 190, about 190 to about 200, about 200 to about 300, about 300 to about 400, about 400 to about 500, or about 500 to about 1000 Daltons.

[0107] As used herein, the term “salt” refers to acid or base salts of the compounds used in the methods of the present invention. Illustrative examples of acceptable salts are mineral acid (hydrochloric acid, hydrobromic acid, phosphoric acid, and the like) salts, organic acid (acetic acid, propionic acid, glutamic acid, citric acid and the like) salts, quaternary ammonium (methyl iodide, ethyl iodide, and the like) salts.

[0108] The term “pharmaceutically acceptable salts” is meant to include salts of the active compounds that are prepared with relatively nontoxic acids or bases, depending on the particular substituents found on the compounds described herein. When compounds of the present invention contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salt, or a similar salt. When compounds of the present invention contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic, or phosphorous acids and the like, as well as the salts derived from relatively nontoxic organic acids like acetic, propionic, isobutyric, maleic, malonic, benzoic, succinic, suberic, fumaric, lactic, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, oxalic, methanesulfonic, and the like. Also included are salts of amino acids such as arginate and the like, and salts of organic acids like glucuronic or galactunoric acids and the like (see, for example, Berge et al., “Pharmaceutical Salts”, Journal of Pharmaceutical Science, 1977, 66, 1-19). Certain specific compounds of the present invention contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts.

[0109] Thus, the compounds of the present invention may exist as salts, such as with pharmaceutically acceptable acids. The present invention includes such salts. Non-limiting examples of such salts include hydrochlorides, hydrobromides, phosphates, sulfates, methanesulfonates, nitrates, maleates, acetates, citrates, fumarates, proprionates, tartrates (e.g., (+)-tartrates, (-)-tartrates, or mixtures thereof including racemic mixtures), succinates, benzoates, and salts with amino acids such as glutamic acid, and quaternary ammonium salts(e.g. methyl iodide, ethyl iodide, and the like). These salts may be prepared by methods known to those skilled in the art.

[0110] The neutral forms of the compounds are preferably regenerated by contacting the salt with a base or acid and isolating the parent compound in the conventional manner. The parent form of the compound may differ from the various salt forms in certain physical properties, such as solubility in polar solvents.

[0111] In addition to salt forms, the present invention provides compounds, which are in a prodrug form. Prodrugs of the compounds described herein are those compounds that readily undergo chemical changes under physiological conditions to provide the compounds of the present invention. Prodrugs of the compounds described herein may be converted in vivo after administration. Additionally, prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an ex vivo environment, such as, for example, when contacted with a suitable enzyme or chemical reagent.

[0112] Certain compounds of the present invention can exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, the solvated forms are equivalent to unsolvated forms and are encompassed within the scope of the present invention. Certain compounds of the present invention may exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the uses contemplated by the present invention and are intended to be within the scope of the present invention.

[0113] A “pharmaceutical composition” as used herein describes a composition containing a therapeutic dose of an active drug ingredient with various inactive ingredients (i.e., excipients, carrier, diluent) which ensure proper delivery, stability, and / or dosage.

[0114] “Pharmaceutically acceptable excipient” and “pharmaceutically acceptable carrier” and “pharmaceutically acceptable diluent” and “pharmaceutically acceptable ingredient” refer to a substance that aids the administration of an active agent to and absorption by a subject and can be included in the compositions of the present invention without causing a significant adverse toxicological effect on the patient. Non-limiting examples of pharmaceutically acceptable excipients include water, binders, lactose, sugar substitute, povidone, colloidal sio, flavoring agents, hydroxypropyl cellulose, disintegrants, microcrystalline cellulose, coatings, fillers, benzyl alcohol, sodium croscarmellose, gelatin, polyethylene glycol, calcium phosphate, sodium starch glycolate, colorants, magnesium stearate, calcium carbonate, crospovidone, gildants, pregelantinized starch, and the like. Non-limiting examples of pharmaceutically acceptable cariers include hydroxypropyl-0-cyclodextrin, Mannitol,Lactose, Sorbitol, Dextrose, Maltose, Sucrose, Fructose, Trehalose, Polyethylene glycol (PEG), Poloxamer (e.g., Poloxamer 188, Poloxamer 407), Hydroxypropyl-P-cyclodextrin, Microcrystalline cellulose. Calcium carbonate, Calcium phosphate, Lipid-based solid carriers (e.g., solid lipid nanoparticles, lipid powders), Polymeric carriers (e.g., poly(lactic-co-gly colic acid), polyvinyl alcohol), and the like. Non-limiting examples of pharamaceutically acceptable diluents include microcrystalline cellulose, calcium stearate, povidone, stearic acid, dextrin, lactose monohydrate, sodium stearyl fumerate, mannitol, lactose, pregelantinized starch, aminobenzoate sodium, gelatin, polysorbates, sucrose, calcium phosphate, polyethylene glycol, starch, crospovidone, hydroxypropyl cellulose, sodium chloride, and the like. Such preparations can be sterilized and, if desired, mixed with auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, and / or aromatic substances and the like that do not deleteriously react with the compounds of the invention. One of skill in the art will recognize that other pharmaceutical excipients, carriers, and / or diluents are useful in the present invention.

[0115] As used herein, the term “formulated” and “formulation” refers to the combination of different pharmaceutically acceptable ingredients to produce a final medicinal product to be delivered to a patient in need thereof via a specific method of administration.

[0116] The terms “treating”, or “treatment” refers to any indicia of success in the therapy or amelioration of an injury, disease, pathology or condition, including any objective or subjective parameter such as abatement; remission; diminishing of symptoms or making the injury, pathology or condition more tolerable to the patient; slowing in the rate of degeneration or decline; making the final point of degeneration less debilitating; improving a patient’s physical or mental well-being. The treatment or amelioration of symptoms can be based on objective or subjective parameters; including the results of a physical examination, neuropsychiatric exams, and / or a psychiatric evaluation. The term "treating" and conjugations thereof, may include prevention of an injury, pathology, condition, or disease. In embodiments, treating is preventing. In embodiments, treating does not include preventing.

[0117] “Patient,” “subject,” “patient in need thereof,” and “subject in need thereof’ are herein used interchangeably and refer to a living organism suffering from or prone to a disease or condition that can be treated by administration of a pharmaceutical composition as provided herein. Non-limiting examples include humans, other mammals, bovines, rats, mice, dogs, monkeys, goat, sheep, cows, deer, and other non-mammalian animals. In some embodiments, the patient is human.

[0118] An “effective amount” may be an amount sufficient for a compound to accomplish a stated purpose relative to the absence of the compound (e.g. achieve the effect for which it is administered, treat a disease, reduce enzyme activity, increase enzyme activity, reduce a signaling pathway, or reduce one or more symptoms of a disease or condition). An example of an “effective amount” may be an amount sufficient to contribute to the treatment, prevention, or reduction of a symptom or symptoms of a disease, which could also be referred to as a “therapeutically effective amount.” A “reduction” of a symptom or symptoms (and grammatical equivalents of this phrase) means decreasing of the severity or frequency of the symptom(s), or elimination of the symptom(s). A “prophylactically effective amount” of a drug may be an amount of a drug that, when administered to a subject, will have the intended prophylactic effect, e.g., preventing or delaying the onset (or reoccurrence) of an injury, disease, pathology or condition, or reducing the likelihood of the onset (or reoccurrence) of an injury, disease, pathology, or condition, or their symptoms. The full prophylactic effect does not necessarily occur by administration of one dose, and may occur only after administration of a series of doses. Thus, a prophylactically effective amount may be administered in one or more administrations. An “activity decreasing amount,” as used herein, refers to an amount of inhibitor required to decrease the activity of an enzyme and / or protein relative to the absence of the inhibitor. A “function disrupting amount,” as used herein, refers to the amount of inhibitor required to disrupt the function of an enzyme and / or protein relative to the absence of the inhibitor. The exact amounts will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques.

[0119] For any compound described herein, the therapeutically effective amount can be initially determined from cell culture assays. Target concentrations will be those concentrations of active compound(s) that are capable of achieving the methods described herein, as measured using the methods described herein or known in the art.

[0120] As is well known in the art, therapeutically effective amounts for use in humans can also be determined from animal models. For example, a dose for humans can be formulated to achieve a concentration that has been found to be effective in animals. The dosage in humans can be adjusted by monitoring compounds effectiveness and adjusting the dosage upwards or downwards, as described above. Adjusting the dose to achieve maximal efficacy in humans based on the methods described above and other methods is well within the capabilities of the ordinarily skilled artisan.

[0121] Dosages may be varied depending upon the requirements of the patient and the compound being employed. The dose administered to a patient, in the context of the presentinvention should be sufficient to effect a beneficial therapeutic response in the patient over time, i.e., a therapeutic dose. The size of the dose also will be determined by the existence, nature, and extent of any adverse side-effects. Determination of the proper dosage for a particular situation is within the skill of the practitioner. Generally, treatment may be initiated with smaller dosages which are less than the optimum dose of the compound. Thereafter, the dosage may be increased by small increments until the optimum effect under the circumstances may be reached. Dosage amounts and intervals can be adjusted individually to provide levels of the administered compound effective for the particular clinical indication being treated. This will provide a therapeutic regimen that may be commensurate with the severity of the individual's disease state.

[0122] Dosage amounts and intervals can be adjusted individually to provide levels of the administered compound effective for the particular clinical indication being treated. This will provide a therapeutic regimen that may be commensurate with the severity of the individual's disease state.

[0123] “Selective” or “selectivity” or the like of a compound refers to the compound’s ability to discriminate between molecular targets. “Specific”, “specifically”, “specificity”, or the like of a compound refers to the compound’s ability to cause a particular action, such as inhibition, to a particular molecular target with minimal or no action to other proteins in the cell.

[0124] As used herein, the term "cancer" refers to all types of cancer including but not limited to neoplasm, or malignant tumors found in mammals, including leukemia, carcinomas and sarcomas.

[0125] Cancer model organism, as used herein, may be an organism exhibiting a phenotype indicative of cancer, or the activity of cancer causing elements, within the organism. The term cancer is defined above. A wide variety of organisms may serve as cancer model organisms, and include for example, cancer cells and mammalian organisms such as rodents (e.g. mouse or rat) and primates (such as humans). Cancer cell lines are widely understood by those skilled in the art as cells exhibiting phenotypes or genotypes similar to in vivo cancers. Cancer cell lines as used herein includes cell lines from animals (e.g. mice) and from humans.

[0126] An “anticancer agent” as used herein refers to a molecule (e.g. compound, peptide, protein, nucleic acid, antibody) used to treat cancer through destruction or inhibition of cancer cells or tissues. Anticancer agents may be selective for certain cancers or certaintissues. In embodiments, anticancer agents herein may include epigenetic inhibitors and multi- or specific inhibitors.

[0127] Utilizing the teachings provided herein, an effective prophylactic or therapeutic treatment regimen can be planned that does not cause substantial toxicity and yet may be effective to treat the clinical symptoms demonstrated by the particular patient. This planning may involve the careful choice of active compound by considering factors such as compound potency, relative bioavailability, patient body weight, presence and severity of adverse side effects, preferred mode of administration and the toxicity profile of the selected agent.

[0128] In terms of example compounds, the identifier “A” refers to the example compound “C38,” the identifier “B” refers to the example compound '‘Cl 1,” the identifier “C” refers to the example compound “C43,” the identifier “D” refers to the example compound “Cl 2.” Compounds

[0129] In some embodiments the small molecule inhibitors may have a structure of Formula (I):R2

[0130] In some embodiments, L1may be a bond to L1A.

[0131] In some embodiments, L1may be -SOniiL1A- wherein nil may be an integer from 0 -4 (e.g., -SL1A-, -SOL1A-, -SChL1A-, -SO3L1A-, -SO4L1A-). In some embodiments, L1may be -SOniiN(CX3)L1A-, (e.g., -SOniiN(CF3)L1A-, -SOniiN(CCh)L1A-, -SOniiN(CBr3)L1A-, -SOniiN(CI3)L1A-). In some embodiments, L1may be -SOniiN(CHX2)L1A-, (e.g., SOniiN(CHF2)L1A-, -SOniiN(CHCl2)L1A-, -SOniiN(CHBr2)L1A-, -SOniiN(CHI2)L1A-). In some embodiments, L1may be -SOniiN(CH2X)L1A-, (e.g., SOniiN(CH2F)L1A-, -SOniiN(CH2Cl)L1A-, -SOniiN(CH2Br)L1A-, -SOniiN(CH2I)L1A-). In some embodiments, L1may be -SOniiN(COOH)L1A-. In some embodiments, L1may be -SOniiN(CONH2)L1A- Insome embodiments, L1may be -SOniiN(substituted alkyl)L1A-. In some embodiments, L1may be -SOniiN(unsubstituted alkyl)L1A-. In some embodiments, L1may be -SOniiN(substituted heteroalkyl)L1A-. In some embodiments. L1may be -SOniiN(unsubstituted heteroalkyl)L1A-. In some embodiments, L1may be -SOniiN(substituted cycloalkyl)L1A- In some embodiments, L1may be -SOniiN(unsubstituted cycloalkyl)L1A-. In some embodiments, L1may be -SOniiN(substituted heterocycloalkyl)L1A-. In some embodiments, L1may be -SOniiN(unsubstituted heterocycloalkyl)L1A-. In some embodiments, L1may be -SOniiN(substituted aryl)L1A-. In some embodiments, L1may be -SOniiN(unsubstituted aryl)L1A-. In some embodiments, L1may be -SOniiN(substituted heteroaryl)L1A-. In some embodiments, L1may be -SOniiN(unsubstituted heteroaryl)L1A-.

[0132] In some embodiments, L1may be -SOv11NR11L1A- wherein vl 1 may be an integer from 1 to 2 (e.g., -SONRnL1A-, -SO2NRnL1A-). In some embodiments, L1may be -SOviiN(CX3)L1A-, (e.g., -SOviiN(CF3)L1A-, -SOviiN(CCl3)L1A-, -SOviiN(CBr3)L1A-, -SOviiN(CI3)L1A-). In some embodiments, L1may be -SOviiN(CHX2)L1A-, (e.g., SOviiN(CHF2)L1A-, -SOviiN(CHCl2)L1A-, -SOviiN(CHBr2)L1A-, -SOviiN(CHI2)L1A-). In some embodiments, L1may be -SOviiN(CH2X)L1A-, (e.g., SOviiN(CH2F)L1A-, -SOviiN(CH2Cl)L1A-, -SOviiN(CH2Br)L1A-, -SOviiN(CH2I)L1A-). In some embodiments, L1may be -SOviiN(COOH)L1A-. In some embodiments, L1may be -SOviiN(CONH2)L1A- In some embodiments, L1may be -SOviiN(substituted alkyl)L1A-. In some embodiments, L1may be -SOviiN(unsubstituted alkyl)L1A-. In some embodiments, L1may be -SOviiN(substituted heteroalkyl)L1A-. In some embodiments. L1may be -SOviiN(unsubstituted heteroalkyl)L1A-. In some embodiments, L1may be -SOviiN(substituted cycloalkyl)L1A-. In some embodiments, L1may be -SOviiN(unsubstituted cycloalkyl)L1A-. In some embodiments, L1may be -SOviiN(substituted heterocycloalkyl)L1A-. In some embodiments, L1may be -SOviiN(unsubstituted heterocycloalkyl)L1A-. In some embodiments, L1may be -SOviiN(substituted aryl)L1A-. In some embodiments, L1may be -SOviiN(unsubstituted aryl)L1A-. In some embodiments, L1may be -SOviiN(substituted heteroaryl)L1A-. In some embodiments, L1may be -SOviiN(unsubstituted heteroaryl)L1A-.

[0133] In some embodiments, L1may be -NHC(O)NR11L1A-. In some embodiments, L1may be -NHC(O)N(CX3)L1A-, (e.g., -NHC(O)N(CF3)L1A-, -NHC(O)N(CCl3)L1A-, -NHC(O)N(CBr3)L1A-, -NHC(O)N(CI3)L1A-). In some embodiments, L1may be -NHC(O)N(CHX2)L1A-, (e.g., -NHC(O)N(CHF2)L1A-, -NHC(O)N(CHCl2)L1A-, -NHC(O)N(CHBr2)L1A-, -NHC(O)N(CHI2)L1A-). In some embodiments, L1may be -NHC(O)N(CH2X)L1A-. (e.g., -NHC(O)N(CH2F)L1A-, -NHC(O)N(CH2C1)L1A-, -NHC(0)N(CH2Br)L1A-, -NHC(0)N(CH2l)L1A-). In some embodiments, L1may be -NHC(O)N(COOH)L1A-. In some embodiments, L1may be -NHC(O)N(CONH2)L1A-. In some embodiments, L1may be -NHC(O)N(substituted alkyl)L1A-. In some embodiments. L1may be — NHC(O)N (unsubstituted alkyl)L1A-. In some embodiments, L1may be -NHC(O)N(substituted heteroalkyl)L1A-. In some embodiments, L1may be -NHC(O)N(unsubstitutedheteroalkyl)L1A-. In some embodiments, L1may be -NHC(O)N(substituted cycloalkyl)L1A-. In some embodiments, L1may be -NHC(O)N(unsubstituted cycloalkyl)L1A-. In some embodiments, L1may be -NHC(O)N(substituted heterocycloalkyl)L1A-. In some embodiments, L1may be -NHC(O)N(unsubstituted heterocycloalkyl)L1A-. In some embodiments, L1may be -NHC(O)N(substituted aryl)L1A-. In some embodiments, L1may be -NHC(O)N(unsubstituted aryl)L1A-. In some embodiments, L1may be -NHC(O)N(substituted heteroaryl)L1A-. In some embodiments, L1may be -NHC(O)N(unsubstituted heteroaryl)L1A-.

[0134] In some embodiments, L1may be -NR11L1A-. In some embodiments, L1may be -N(CX3)L1A-, (e.g., -N(CF3)L1A-, -N(CC13)L1A-, -N(CBr3)L1A-, -N(CI3)L1A-). In some embodiments, L1may be -N(CHX2)L1A-, (e.g., -N(CHF2)L1A-, -N(CHC12)L1A-, -N(CHBr2)L1A-, -N(CHl2)L1A-). In some embodiments, L1may be -N(CH2X)L1A-. (e.g., -N(CH2F)L1A-, -N(CH2C1)L1A-, -N(CH2Br)L1A-, -N(CH2I)L1A-). In some embodiments, L1may be -N(COOH)L1A-. In some embodiments, L1may be -N(CONH2)L1A-. In some embodiments, L1may be -N(substituted alkyl)L1A-. In some embodiments, L1may be -N(unsubstituted alkyl)L1A- In some embodiments, L1may be -N(substituted heteroalky 1)L1A-. In some embodiments, L1may be -N(unsubstituted heteroalkyl)L1A-. In some embodiments, L1may be -N(substituted cycloalkyl)L1A-. In some embodiments, L1may be -N(unsubstituted cycloalkyl)L1A-. In some embodiments, L1may be -N(substituted heterocycloalkyl)L1A-. In some embodiments, L1may be -N(unsubstituted heterocycloalkyl)L1A-. In some embodiments, L1may be -N(substituted aryl)L1A-. In some embodiments, L1may be -N(unsubstituted aryl)L1A-. In some embodiments, L1may be -N(substituted heteroaryl)L1A-. In some embodiments, L1may be -N(unsubstituted heteroaryl)L1A-.

[0135] In some embodiments, L1may be -C(O)L1A-.

[0136] In some embodiments, L1may be -C(O)OL1A-.

[0137] In some embodiments, L1may be -C(O)NR11L1A-. In some embodiments, L1may be -C(O)N(CX3)L1A-, (e.g., -C(O)N(CF3)L1A-, -C(O)N(CC13)L1A-, -C(O)N(CBr3)L1A-. -C(O)N(CI3)L1A-). In some embodiments, L1may be -C(O)N(CHX2)L1A-, (e.g., -C(O)N(CHF2)L1A-, -C(0)N(CHC12)L1A-, -C(O)N(CHBr2)L1A-, -C(O)N(CHI2)L1A-). In some embodiments, L1may be -C(O)N(CH2X)L1A-, (e.g., -C(O)N(CH2F)L1A-, -C(O)N(CH2C1)L1A-, -C(O)N(CH2Br)L1A-, -C(O)N(CH21)L1A-). In some embodiments, L1may be -C(O)N(COOH)L1A-. In some embodiments, L1may be -C(O)N(CONH2)L1A-. In some embodiments, L1may be -C(O)N(substituted alkyl)L1A-. In some embodiments, L1may be -C(O)N(unsubstituted alky 1)1?A-. In some embodiments, L1may be -C(O)N(substituted heteroalkyl)L1A-. In some embodiments. L1may be -C(O)N(unsubstituted heteroalkyl)L1A-. In some embodiments, L1may be -C(O)N(substituted cycloalkyl)L1A-. In some embodiments, L1may be -C(O)N(unsubstituted cycloalkyl)L1A-. In some embodiments, L1may be -C(O)N(substituted heterocycloalkyl)L1A-. In some embodiments, L1may be -C(O)N(unsubstituted heterocycloalkyl)L1A-. In some embodiments, L1may be -C(O)N(substituted aryl)L1A-. In some embodiments, L1may be -C(O)N(unsubstituted aryl)L1A-. In some embodiments, L1may be -C(O)N(substituted heteroaryl)L1A-. In some embodiments, L1may be -C(O)N(unsubstituted heteroaryl)L1A-.

[0138] In some embodiments, L1may be -OL1A-.

[0139] In some embodiments, L1may be -NRnSO2L1A-. In some embodiments, L1may be -N(CX3)SO2L1A-. (e.g.. -N(CF3)SO2L1A-, -N(CC13)SO2L1A-. -N(CBr3)SO2L1A-, -N(CI3)SO2L1A-). In some embodiments, L1may be -N(CHX2)SO2L1A-, (e.g., -N(CHF2)SO2L1A-, -N(CHC12)SO2L1A-, -N(CHBr2)SO2L1A-, -N(CHI2)SO2L1A-). In some embodiments, L1may be -N(CH2X)SO2L1A-, (e.g.,-N(CH2F)SO2L1A-, -N(CH2C1)SO2L1A-, -N(CH2Br)SO2L1A-. -N(CH2I)SO2L1A-). In some embodiments, L1may be -N(COOH)SO2L1A-. In some embodiments, L1may be -N(CONH2)SO2L1A-. In some embodiments, L1may be -N(substituted alkyl)SO2L1A-. In some embodiments, L1may be -N(unsubstituted alkyl)SO2L1A-. In some embodiments, L1may be -N(substituted heteroalkyl)SO2L1A-. In some embodiments, L1may be -N(unsubstituted heteroalkyl)SO2L1A- In some embodiments, L1may be -N(substituted cycloalkyl)SO2L1A-. In some embodiments. L1may be -N(unsubstituted cycloalkyl)SO2L1A-. In some embodiments, L1may be -N(substituted heterocycloalkyl)SO2L1A-. In some embodiments, L1may be -N(unsubstituted heterocycloalkyl)SO2L1A-. In some embodiments, L1may be -N(substituted aryl)SO2L1A-. In some embodiments, L1may be -N(unsubstituted aryl)SO2L1A-. In some embodiments, L1may be -N (substituted heteroaryl)SO2L1A-. In some embodiments, L1may be -N (unsubstituted heteroaryl)SO2L1A-

[0140] In some embodiments, L1may be -NRnC(O)L1A-. In some embodiments, L1may be -N(CX3)C(O)L1A-, (e.g., -N(CF3)C(O)L1A-, -N(CC13)C(O)L1A-, -N(CBr3)C(O)L1A-. -N(Ch)C(O)L1A-). In some embodiments, L1may be -N(CHX2)C(O)L1A-, (e.g., -N(CHF2)C(O)L1A-, -N(CHC12)C(O)L1A-, -N(CHBr2)C(O)L1A-, -N(CHI2)C(O)L1A-). In some embodiments, L1may be -N(CH2X)C(O)L1A-. (e.g..-N(CH2F)C(O)L1A-, -N(CH2C1)C(O)L1A-, -N(CH2Br)C(O)L1A-, -N(CH2I)C(O)L1A-). In some embodiments, L1may be -N(COOH)C(O)L1A-. In some embodiments, L1may be -N(CONH2)C(O)L1A-. In some embodiments, L1may be -N(substituted alkyl)C(O)L1A-. In some embodiments, L1may be -N(unsubstituted alkyl)C(O)L1A-. In some embodiments, L1may be -N(substituted heteroalkyl)C(O)L1A-. In some embodiments, L1may be -N (unsubstituted heteroalkyl)C(O)L1A-. In some embodiments, L1may be -N(substituted cycloalkyl)C(O)L1A-. In some embodiments, L1may be -N(unsubstituted cycloalkyl)C(O)L1A-. In some embodiments, L1may be -N(substituted heterocycloalkyl)C(O)L1A- In some embodiments, L1may be -N(unsubstituted heterocycloalkyl)C(O)L1A-. In some embodiments, L1may be -N(substituted aryl)C(O)L1A-. In some embodiments, L1may be -N(unsubstituted aryl)C(O)L1A-. In some embodiments, L1may be -N(substituted heteroaryl)C(O)L1A-. In some embodiments, L1may be -N(unsubstituted heteroaryl)C(O)L1A-.

[0141] In some embodiments, L1may be -NR11C(O)OL1A-. In some embodiments, L1may be -N(CX3)C(O)OL1A-, (e.g.. -N(CF3)C(O)OL1A-. -N(CC13)C(O)OL1A-. -N(CBr3)C(O)OL1A-, -N(CI3)C(O)OL1A-). In some embodiments, L1may be -N(CHX2)C(O)OL1A-, (e.g., -N(CHF2)C(O)OL1A-, -N(CHCh)C(O)OL1A-, -N(CHBr2)C(O)OL1A-, -N(CHI2)C(O)OL1A-). In some embodiments, L1may be -N(CH2X)C(O)OL1A-, (e.g.,-N(CH2F)C(O)OL1A-, -N(CH2C1)C(O)OL1A-, -N(CH2Br)C(O)OL1A-, -N(CH2I)C(O)OL1A-). In some embodiments, L1may be -N(COOH)C(O)OL1A-. In some embodiments, L1may be -N(CONH2)C(O)OL1A-. In some embodiments, L1may be -N(substituted alkyl)C(O)OL1A-. In some embodiments, L1may be -N(unsubstituted alkyl)C(O)OL1A-. In some embodiments, L1may be -N(substituted heteroalkyl)C(O)OL1A-. In some embodiments, L1may be -N(unsubstituted heteroalkyl)C(O)OL1A-. In some embodiments, L1may be -N (substituted cycloalkyl)C(O)OL1A-. In some embodiments, L1may be -N(unsubstituted cycloalkyl)C(O)OL1A-. In some embodiments, L1may be -N(substituted heterocycloalkyl)C(O)OL1A-. In some embodiments, L1may be -N(unsubstituted heterocycloalkyl)C(O)OL1A-. In some embodiments, L1may be -N(substituted aryl)C(O)OL1A-. In some embodiments, L1may be -N(unsubstituted aryl)C(O)OL1A- In some embodiments, L1may be -N(substituted heteroaryl)C(O)OL1A-. In some embodiments, L1may be -N(unsubstituted heteroaryl)C(O)OL1A-.

[0142] In some embodiments, L1may be -NRnOL1A-. In some embodiments, L1may be -N(CXa)OL1A-, (e.g., -N(CF3)OL1A-, -N(CC13)OL1A-. -N(CBr3)OL1A-, -N(CI3)OL1A-). In some embodiments, L1may be -N(CHX2)OL1A-, (e.g., -N(CHF2)OL1A-, -N(CHC12)OL1A-, -N(CHBr2)OL1A-, -N(CHl2)OL1A-). In some embodiments, L1may be -N(CH2X)OL1A-, (e.g.,-N(CH2F)OL1A-, -N(CH2C1)OL1A-, -N(CH2Br)OL1A-, -N(CH2I)OL1A-). In some embodiments, L1may be -N(COOH)OLIA-. In some embodiments, L1may be -N(CONH2)OL1A-. In some embodiments, L1may be -N(substituted alkyl)OL1A-. In some embodiments, L1may be -N(unsubstituted alkyl)OL1A-. In some embodiments, L1may be -N(substituted heteroalkyl)OL1A-. In some embodiments, L1may be -N(unsubstituted heteroalkyl)OL1A-. In some embodiments, L1may be -N(substituted cycloalkyl)OL1A-. In some embodiments, L1may be -N(unsubstituted cycloalkyl)OL1A-. In some embodiments, L1may be -N(substituted heterocycloalkyl)OL1A-. In some embodiments, L1may be -N(unsubstituted heterocycloalkyl)OL1A-. In some embodiments, L1may be -N(substituted aryl)OL1A-. In some embodiments, L1may be -N(unsubstituted aryl)OL1A-. In some embodiments, L1may be -N(substituted heteroaryl)OL1A-. In some embodiments, L1may be -N(unsubstituted heteroaryl)OL1A-.

[0143] In some embodiements, L1may be -SL1A-.

[0144] In some embodiments, L1may be -substituted alkyl-L1A-. In some embodiments, L1may be -unsubstituted alkyl-L1A-. In some embodiments, L1may be -substituted heteroalkyl-L1A-. In some embodiments, L1may be -unsubstituted heteroalkyl-L1A-. In some embodiments, L1may be -substituted alkylene-L1A-. In some embodiments. L1may be -unsubstituted alkylene-L1A-. In some embodiments, L1may be -substituted heteroalkylene-L1A-. In some embodiments, L1may be -unsubstituted heteroalkylene-L1A-. In some embodiments, L1may be -substituted cycloalkylene-L1A-. In some embodiments, L1may be -unsubstituted cycloalkylene-L1A-. In some embodiments, L1may be -substituted heterocycloalkylene-L1A-. In some embodiments, L1may be -unsubstituted heterocycloalkylene-L1A-. In some embodiments, L1may be -unsubstituted arylene-L1A-. In some embodiments, L1may be -unsubstituted arylene-L1A-. In some embodiments, L1may be -substituted heteroarylene-L1A-. In some embodiments, L1may be -unsubstituted heteroarylene-L1A-.

[0145] In some embodiments, R1may be absent. In some embodiments, R1may be hydrogen. In some embodiments, R1may be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R1may be -CX3, (e.g., CFs, CCls, CBr3, CI3). In some embodiments, R1may be -CHX1^ (e.g., -CHF2, -CHC12, -CHBr2, -CHI2). In some embodiments, R1may be -CH2X1, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R1may be -OCXJ3, (e.g., -OCF3, -OCCI3. -OCBrs, -OCI3). In some embodiments, R1may be -OCHX^, (e.g.. -OCHF2, -OCHCh, -OCHBr2, -OCHh). In some embodiments, R1may be -OCH2X, (e g., -OCH2F, -OCH2CI, -OCFBBr, -OCH2I). In some embodiments, R1may be -OCH3.

[0146] In some embodiments, R1may be -OCH2R1A. In some embodiments, R1Amay be hydrogen. In some embodiments, R1Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R1Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R1Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R1Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R1Amay be -COOH. In some embodiments, R1Amay be substituted alkyl. In some embodiments, R1Amay be unsubstituted alkyl. In some embodiments, R1Amay be substituted heteroalkyl. In some embodiments, R1Amay be unsubstituted heteroalkyl. In some embodiments, R1Amay be substituted cycloalkyl. In some embodiments, R1Amay be unsubstituted cycloalkyl. In some embodiments, R1Amay be substituted heterocycloalkyl. In some embodiments, R1Amay be unsubstituted heterocycloalkyl. In some embodiments, R1Amay be substituted aryl. In some embodiments, R1Amay be unsubstituted aryl. In some embodiments, R1Amay be substituted heteroaryl. In some embodiments, R1Amay be unsubstituted heteroaryl.

[0147] In some embodiments, R1may be -N3. In some embodiments, R1may be -CN.

[0148] In some embodiments, R1may be -SOniiR1Dwherein nil may be an integer from 0 -4 (e.g., -SR1D, -SOR1D, -SChR113, -SOSR1D, -SO4R1D). In some embodiments, R1Dmay be hydrogen. In some embodiments, R1Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R1Dmay be -CX3. (e.g., -CF3. -CCl3, -CBr₃, -CI₃). In some embodiments, R1Dmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R1Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R1Dmay be -COOH. In some embodiments, R1Dmay be substituted alkyl. In some embodiments, R1Dmay be unsubstituted alkyl. In some embodiments, R1Dmay be substituted heteroalkyl. In some embodiments, R1Dmay be unsubstituted heteroalkyl. In some embodiments, R1Dmay be substituted cycloalkyl. In some embodiments, R1Dmay be unsubstituted cycloalkyl. In some embodiments, R1Dmay be substituted heterocycloalkyl. In some embodiments, R1Dmay be unsubstituted heterocycloalkyl. In some embodiments, R1Dmay be substituted aryl. In some embodiments, R1Dmay be unsubstituted aryl. In some embodiments, R1Dmay be substituted heteroaryl. In some embodiments, R1Dmay be unsubstituted heteroaryl.

[0149] In some embodiments, R1may be SOv1NR1AR1Bwhereinvimay be an integer from 1 to 2 (e.g., -SONR1AR1B, -SO2NR1AR1B). In some embodiments, R1Amay be hydrogen. In some embodiments, R1Amay be halogen, (e.g., -F, -Br, -CL -1). In some embodiments, R1Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R1Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R1Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R1Amay be -COOH. In some embodiments, R1Amay be substituted alkyl. In some embodiments, R1Amay be unsubstituted alkyl. In some embodiments, R1Amay be substituted heteroalkyl. In some embodiments, R1Amay be unsubstituted heteroalkyl. In some embodiments, R1Amay be substituted cycloalkyl. In some embodiments, R1Amay be unsubstituted cycloalkyl. In some embodiments, R1Amay be substituted heterocycloalkyl. In some embodiments, R1Amay be unsubstituted heterocycloalkyl. In some embodiments, R1Amay be substituted aryl. In some embodiments, R1Amay be unsubstituted aryl. In some embodiments, R1Amay be substituted heteroaryl. In some embodiments, R1Amay be unsubstituted heteroaryl. In some embodiments, R1Bmay be hydrogen. In some embodiments, R1Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R1Dmay be -CX3. (e.g., -CF3. -CCl₃, -CBr₃, -CI₃). In some embodiments, R1Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI₂). In some embodiments, R1Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R1Bmay be -COOH. In some embodiments, R1Bmay be substituted alkyl. In some embodiments, R1Bmay be unsubstituted alkyl. In some embodiments, R1Bmay be substituted heteroalkyl. In some embodiments, R1Bmay be unsubstituted heteroalkyl. In some embodiments, R1Bmay be substituted cycloalkyl. In some embodiments, R1Bmay be unsubstituted cycloalkyl. In some embodiments, R1Bmay be substituted heterocycloalkyl. In some embodiments, R1Bmay be unsubstituted heterocycloalkyl. In some embodiments, R1Bmay be substituted aryl. In some embodiments, R1Bmay be unsubstituted aryl. In some embodiments, R1Bmay be substituted heteroaryl. In some embodiments, R1Bmay be unsubstituted heteroaryl.

[0150] In some embodiments, R1may be -NHC(O)NR1AR1B. In some embodiments, R1Amay be hydrogen. In some embodiments, R1Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R1Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R1Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R1Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R1Amay be -COOH. In some embodiments, R1Amay be substituted alkyl. In some embodiments, R1Amay be unsubstituted alkyl. In some embodiments, R1Amay be substituted heteroalkyl. In some embodiments, R1Amay be unsubstituted heteroalkyl. In some embodiments, R1Amay besubstituted cycloalkyl. In some embodiments, R1Amay be unsubstituted cycloalkyl. In some embodiments, R1Amay be substituted heterocycloalkyl. In some embodiments, R1Amay be unsubstituted heterocycloalkyl. In some embodiments, R1Amay be substituted aryl. In some embodiments, R1Amay be unsubstituted aryl. In some embodiments, R1Amay be substituted heteroaryl. In some embodiments, R1Amay be unsubstituted heteroaryl. In some embodiments, R1Rmay be hydrogen. In some embodiments, R, Bmay be halogen, (e.g., -F, -Br, -Cl. -I). In some embodiments. R1Bmay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R1Bmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R1Rmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R1Rmay be -COOH. In some embodiments, R1Bmay be substituted alkyl. In some embodiments, R1Rmay be unsubstituted alkyl. In some embodiments. R1Rmay be substituted heteroalkyl. In some embodiments, R1Bmay be unsubstituted heteroalkyl. In some embodiments, R1Bmay be substituted cycloalkyl. In some embodiments, R1Bmay be unsubstituted cycloalkyl. In some embodiments, R1Bmay be substituted heterocycloalkyl. In some embodiments, R1Bmay be unsubstituted heterocycloalkyl. In some embodiments. R1Bmay be substituted aryl. In some embodiments, R1Dmay be unsubstituted aryl. In some embodiments, R1Bmay be substituted heteroaryl. In some embodiments, R1Bmay be unsubstituted heteroaryl.

[0151] In some embodiments, R1may be -N(O)m1wherein m1may be an integer from 1 to 2 (e.g., -N(O), -NO2).

[0152] In some embodiments, R1may be -NR1AR1B. In some embodiments, R1Amay be hydrogen. In some embodiments, R1Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R1Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R1Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R1Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R1Amay be -COOH. In some embodiments, R1Amay be substituted alkyl. In some embodiments. R1Amay be unsubstituted alkyl. In some embodiments, R1Amay be substituted heteroalkyl. In some embodiments, R1Amay be unsubstituted heteroalkyl. In some embodiments, R1Amay be substituted cycloalkyl. In some embodiments, R1Amay be unsubstituted cycloalkyl. In some embodiments, R1Amay be substituted heterocycloalkyl. In some embodiments, R1Amay be unsubstituted heterocycloalkyl. In some embodiments, R1Amay be substituted aryl. In some embodiments, R1Amay be unsubstituted aryl. In some embodiments, R1Amay be substituted heteroaryl. In some embodiments, R1Amay be unsubstituted heteroaryl. In some embodiments, R1Rmay be hydrogen. In some embodiments, R1Bmay be halogen, (e.g.. -F, -Br, -Cl, -I). In some embodiments, R1Bmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R1Bmay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI2). In some embodiments, R1Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R1Bmay be -COOH. In some embodiments, R1Bmay be substituted alkyl. In some embodiments, R1Bmay be unsubstituted alkyl. In some embodiments, R1Bmay be substituted heteroalkyl. In some embodiments. R, Bmay be unsubstituted heteroalkyl. In some embodiments, R1Bmay be substituted cycloalkyl. In some embodiments, R1Bmay’ be unsubstituted cycloalkyl. In some embodiments, R1Bmay be substituted heterocycloalkyl. In some embodiments, R1Bmay be unsubstituted heterocycloalkyl. In some embodiments, R1Bmay be substituted aryl. In some embodiments, R1Bmay be unsubstituted aryl. In some embodiments, R1Bmay be substituted heteroaryl. In some embodiments, R1Bmay be unsubstituted heteroaryl.

[0153] In some embodiments, R1may be -C(O)R1C. In some embodiments, R1Cmay be hydrogen. In some embodiments, R1Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R1Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R1Cmay be -CHX2. (e.g., -CHF2, -CHCl₂, -CHBr2, -CHI2). In some embodiments, R1Cmay be -CH2X, (e g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments. R1Cmay be -COOH. In some embodiments, R1Cmay be substituted alkyl. In some embodiments, R1Cmay be unsubstituted alkyl. In some embodiments, R1Cmay be substituted heteroalkyl. In some embodiments, R1Cmay be unsubstituted heteroalkyl. In some embodiments, R1Cmay be substituted cycloalkyl. In some embodiments, R1Cmay be unsubstituted cycloalkyl. In some embodiments, R1Cmay be substituted heterocycloalkyl. In some embodiments, R1Cmay be unsubstituted heterocycloalkyl. In some embodiments, R1Cmay be substituted aryl. In some embodiments, R1Cmay be unsubstituted aryl. In some embodiments, R1Cmay be substituted heteroaryl. In some embodiments, R1Cmay be unsubstituted heteroaryl.

[0154] In some embodiments, R1may be -C(O)-OR1C. In some embodiments, R1Cmay be hydrogen. In some embodiments, R1Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R1Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R1Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R1Cmay be -CH2X, (e.g., -CH2F, -CH₂Cl, -CH2Br, -CH2I). In some embodiments, R1Cmay be -COOH. In some embodiments, R1Cmay be substituted alkyl. In some embodiments, R1Cmay be unsubstituted alkyl. In some embodiments, R1Cmay be substituted heteroalkyl. In some embodiments, R1Cmay be unsubstituted heteroalkyl. In some embodiments, R1Cmay be substituted cycloalkyl. In some embodiments, R1Cmay be unsubstituted cycloalkyl. In someembodiments, R1Cmay be substituted heterocycloalkyl. In some embodiments, R1Cmay be unsubstituted heterocycloalkyl. In some embodiments, R1Cmay be substituted aryl. In some embodiments, R1Cmay be unsubstituted aryl. In some embodiments, R1Cmay be substituted heteroaryl. In some embodiments, R1Cmay be unsubstituted heteroaryl.

[0155] In some embodiments, R1may be -C(O)NR1AR1B. In some embodiments, R1Amay be hydrogen. In some embodiments, R1Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R1Amay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R1Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R1Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R1Amay be -COOH. In some embodiments, R1Amay be substituted alkyl. In some embodiments, R1Amay be unsubstituted alkyl. In some embodiments, R1Amay be substituted heteroalkyl. In some embodiments, R1Amay be unsubstituted heteroalkyl. In some embodiments, R1Amay be substituted cycloalkyl. In some embodiments, R1Amay be unsubstituted cycloalkyl. In some embodiments, R1Amay be substituted heterocycloalkyl. In some embodiments, R1Amay be unsubstituted heterocycloalkyl. In some embodiments, R1Amay be substituted aryl. In some embodiments, R1Amay be unsubstituted aryl. In some embodiments, R1Amay be substituted heteroaryl. In some embodiments, R1Amay be unsubstituted heteroaryl. In some embodiments, R1Bmay be hydrogen. In some embodiments, R1Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R1Bmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R1Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R1Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br. -CH2I). In some embodiments, R1Bmay be -COOH. In some embodiments, R1Bmay be substituted alkyl. In some embodiments, R1Bmay be unsubstituted alkyl. In some embodiments, R1Bmay be substituted heteroalkyl. In some embodiments, R1Bmay be unsubstituted heteroalkyl. In some embodiments, R1Bmay be substituted cycloalkyl. In some embodiments, R1Bmay be unsubstituted cycloalkyl. In some embodiments, R1Bmay be substituted heterocycloalkyl. In some embodiments, R1Bmay be unsubstituted heterocycloalkyl. In some embodiments, R1Bmay be substituted aryl. In some embodiments, R1Bmay be unsubstituted aryl. In some embodiments, R1Bmay be substituted heteroaryl. In some embodiments, R1Bmay be unsubstituted heteroaryl.

[0156] In some embodiments, R1may be -OR1D. In some embodiments, R1Dmay be hydrogen. In some embodiments, R1Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R1Dmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R1Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R1Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R1Dmay be -COOH. In some embodiments, R1Dmay be substituted alkyl. In some embodiments, R1Dmay be unsubstituted alkyl. In some embodiments. R1Dmay be substituted heteroalkyl. In some embodiments, R1Dmay be unsubstituted heteroalkyl. In some embodiments, R1Umay be substituted cycloalkyl. In some embodiments, R1Dmay be unsubstituted cycloalkyl. In some embodiments, R1Dmay be substituted heterocycloalkyl. In some embodiments, R1Dmay be unsubstituted heterocycloalkyl. In some embodiments. R1Dmay be substituted aryl. In some embodiments. R1Dmay be unsubstituted aryl. In some embodiments, R1Dmay be substituted heteroaryl. In some embodiments, R1Dmay be unsubstituted heteroaryl.

[0157] In some embodiments, R1-NR1ASC>2R1D. In some embodiments, R1Amay be hydrogen. In some embodiments, R1Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R1Amay be -CX3. (e.g., -CF3. -CCl3, -CBr₃, -CI₃). In some embodiments, R1Amay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R1Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R1Amay be -COOH. In some embodiments, R1Amay be substituted alkyl. In some embodiments, R1Amay be unsubstituted alkyl. In some embodiments, R1Amay be substituted heteroalkyl. In some embodiments, R1Amay be unsubstituted heteroalkyl. In some embodiments, R1Amay be substituted cycloalkyl. In some embodiments, R1Amay be unsubstituted cycloalkyl. In some embodiments, R1Amay be substituted heterocycloalkyl. In some embodiments, R1Amay be unsubstituted heterocycloalkyl. In some embodiments, R1Amay be substituted aryl. In some embodiments, R1Amay be unsubstituted aryl. In some embodiments, R1Amay be substituted heteroaryl. In some embodiments, R1Amay be unsubstituted heteroaryl. In some embodiments, R1Dmay be hydrogen. In some embodiments, R1Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R1Dmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R1Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R1Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R1Dmay be -COOH. In some embodiments, R1Dmay be substituted alkyl. In some embodiments, R1Dmay be unsubstituted alkyl. In some embodiments, R1Dmay be substituted heteroalkyl. In some embodiments. R1Dmay be unsubstituted heteroalkyl. In some embodiments, R1Dmay be substituted cycloalkyl. In some embodiments, R1Dmay be unsubstituted cycloalkyl. In some embodiments, R1Dmay be substituted heterocycloalkyl. In some embodiments, R1Dmay be unsubstituted heterocycloalkyl. In some embodiments, R1Dmay be substituted aryl. In some embodiments, R1Dmay be unsubstituted aryl. In someembodiments, R1Dmay be substituted heteroaryl. In some embodiments, R1Dmay be unsubstituted heteroaryl.

[0158] In some embodiments, R1-NR1AC(O)R1C. In some embodiments, R1Amay be hydrogen. In some embodiments, R1Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R1Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R1Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R1Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R1Amay be -COOH. In some embodiments, R1Amay be substituted alkyl. In some embodiments, R1Amay be unsubstituted alkyl. In some embodiments, R1Amay be substituted heteroalkyl. In some embodiments, R1Amay be unsubstituted heteroalkyl. In some embodiments, R1Amay be substituted cycloalkyl. In some embodiments, R1Amay be unsubstituted cycloalkyl. In some embodiments, R1Amay be substituted heterocycloalkyl. In some embodiments, R1Amay be unsubstituted heterocycloalkyl. In some embodiments, R1Amay be substituted aryl. In some embodiments, R1Amay be unsubstituted aryl. In some embodiments, R1Amay be substituted heteroaryl. In some embodiments, R1Amay be unsubstituted heteroaryl. In some embodiments, R1Cmay be hydrogen. In some embodiments, R1Cmay be halogen, (e.g.. -F, -Br, -Cl, -I). In some embodiments, R1Cmay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R1Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI2). In some embodiments, R1Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R1Cmay be -COOH. In some embodiments, R1Cmay be substituted alkyl. In some embodiments, R1Cmay be unsubstituted alkyl. In some embodiments. R1Cmay be substituted heteroalkyl. In some embodiments, R1Cmay be unsubstituted heteroalkyl. In some embodiments, R1Cmay be substituted cycloalkyl. In some embodiments, R1Cmay be unsubstituted cycloalkyl. In some embodiments, R1Cmay be substituted heterocycloalkyl. In some embodiments, R1Cmay be unsubstituted heterocycloalkyl. In some embodiments. R1Cmay be substituted aryl. In some embodiments, R1Cmay be unsubstituted aryl. In some embodiments, R1Cmay be substituted heteroaryl. In some embodiments, R1Cmay be unsubstituted heteroaryl.

[0159] In some embodiments, R1-NR1AC(O)OR1C. In some embodiments, R1Amay be hydrogen. In some embodiments, R1Amay be halogen, (e.g., -F. -Br, -Cl, -I). In some embodiments, R1Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R1Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R1Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R1Amay be -COOH. In some embodiments, R1Amay be substituted alkyl. In some embodiments, R1Amay beunsubstituted alkyl. In some embodiments, R1Amay be substituted heteroalkyl. In some embodiments, R1Amay be unsubstituted heteroalkyl. In some embodiments, R1Amay be substituted cycloalkyl. In some embodiments, R1Amay be unsubstituted cycloalkyl. In some embodiments, R1Amay be substituted heterocycloalkyl. In some embodiments, R1Amay be unsubstituted heterocycloalkyl. In some embodiments, R1Amay be substituted aryl. In some embodiments, R1Amay be unsubstituted aryl. In some embodiments, R1Amay be substituted heteroaryl. In some embodiments, R1Amay be unsubstituted heteroaryl. In some embodiments, R1Cmay be hydrogen. In some embodiments, R1Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R1Cmay be -CX₃, (e.g., -CF₃, -CCl₃, -CBr₃, -CI3). In some embodiments, R1Cmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R1Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R1Cmay be -COOH. In some embodiments, R1Cmay be substituted alkyl. In some embodiments, R1Cmay be unsubstituted alkyl. In some embodiments, R1Cmay be substituted heteroalkyl. In some embodiments, R1Cmay be unsubstituted heteroalkyl. In some embodiments, R1Cmay be substituted cycloalkyl. In some embodiments, R1Cmay be unsubstituted cycloalkyl. In some embodiments. R1Cmay be substituted heterocycloalkyl. In some embodiments, R1Cmay be unsubstituted heterocycloalkyl. In some embodiments, R1Cmay be substituted aryl. In some embodiments, R1Cmay be unsubstituted aryl. In some embodiments, R1Cmay be substituted heteroaryl. In some embodiments, R1Cmay be unsubstituted heteroaryl.

[0160] In some embodiments, R1may be -NR1AOR1C. In some embodiments. R1Amay be hydrogen. In some embodiments, R1Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R1Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R1Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R1Amay be -CH2X, (e g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments, R1Amay be -COOH. In some embodiments, R1Amay be substituted alkyl. In some embodiments, R1Amay be unsubstituted alkyl. In some embodiments, R1Amay be substituted heteroalkyl. In some embodiments, R1Amay be unsubstituted heteroalkyl. In some embodiments, R1Amay be substituted cycloalkyl. In some embodiments, R1Amay be unsubstituted cycloalkyl. In some embodiments, R1Amay be substituted heterocycloalkyl. In some embodiments, R1Amay be unsubstituted heterocycloalkyl. In some embodiments, R1Amay be substituted aryl. In some embodiments, R1Amay be unsubstituted aryl. In some embodiments, R1Amay be substituted heteroaryl. In some embodiments, R1Amay be unsubstituted heteroaryl. In some embodiments, R1Cmay be hydrogen. In some embodiments, R1Cmay be halogen, (e.g.. -F, -Br, -Cl, -I). In some embodiments, R1Cmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R1Cmay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI2). In some embodiments, R1Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R1Cmay be -COOH. In some embodiments, R1Cmay be substituted alkyl. In some embodiments, R1Cmay be unsubstituted alkyl. In some embodiments, R1Cmay be substituted heteroalkyl. In some embodiments. R1Cmay be unsubstituted heteroalkyl. In some embodiments, R1Cmay be substituted cycloalkyl. In some embodiments, R1Cmay’ be unsubstituted cycloalkyl. In some embodiments, R1Cmay be substituted heterocycloalkyl. In some embodiments, R1Cmay be unsubstituted heterocycloalkyl. In some embodiments, R1Cmay be substituted aryl. In some embodiments, R1Cmay be unsubstituted aryl. In some embodiments, R1Cmay be substituted heteroaryl. In some embodiments, R1Cmay be unsubstituted heteroaryl.

[0161] In some embodiments, R1may be substituted alkyl. In some embodiments, R1may be unsubstituted alkyl. In some embodiments, R1may be substituted heteroalkyl. In some embodiments, R1may be unsubstituted heteroalkyl. In some embodiments, R1may be substituted cycloalkyl. In some embodiments, R1may be unsubstituted cycloalkyl. In some embodiments, R1may be substituted heterocycloalkyl. In some embodiments, R1may be unsubstituted heterocycloalkyl. In some embodiments, R1may be substituted aryl. In some embodiments, R1may be unsubstituted aryl. In some embodiments, R1may be substituted heteroaryl. In some embodiments, R1may be unsubstituted heteroaryl.

[0162] In some embodiments, R2may be absent. In some embodiments, R2may be hydrogen. In some embodiments, R2may be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2may be -CX3, (e.g., CF3, CCls, CBn, Ch). In some embodiments, R2may be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R2may be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R2may be -OCX3, (e.g., -OCF3, -OCCI3. -OCBr3, -OCI3). In some embodiments. R2may be -OCHX2, (e.g.. -OCHF2, -OCHCI2, -OCHBr2, -OCHh). In some embodiments, R2may be -OCH2X, (e.g., -OCH2F, -OCH2CI, -OCFBBr, -OCH2I). In some embodiments, R2may be -OCHs.

[0163] In some embodiments, R2may be -OCH2R2A. In some embodiments, R2Amay be hydrogen. In some embodiments, R2Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Amay be -CX3. (e.g.. -CF3. -CCl3, -CBr₃, -CI₃). In some embodiments, R2Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr2, -CHI2). In some embodiments, R2Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R2Amay be -COOH. In some embodiments, R2Amay be substituted alkyl. In some embodiments, R2Amay beunsubstituted alkyl. In some embodiments, R2Amay be substituted heteroalkyl. In some embodiments, R2Amay be unsubstituted heteroalkyl. In some embodiments, R2Amay be substituted cycloalkyl. In some embodiments, R2Amay be unsubstituted cycloalkyl. In some embodiments, R2Amay be substituted heterocycloalkyl. In some embodiments, R2Amay be unsubstituted heterocycloalkyl. In some embodiments, R2Amay be substituted aryl. In some embodiments, R2Amay be unsubstituted aryl. In some embodiments, R2Amay be substituted heteroaryl. In some embodiments, R2Amay be unsubstituted heteroaryl.

[0164] In some embodiments, R2may be -N3, -CN,

[0165] In some embodiments, R2may be -SOn2R2Dwhereinn2may be an integer from 0 - 4 (e.g., -SR2D, -SOR2D, -SO2R2D, -SChR2D, -SO4R2D). In some embodiments, R2Dmay be hydrogen. In some embodiments, R2Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Dmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R2Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R2Dmay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R2Dmay be -COOH. In some embodiments, R2Dmay be substituted alkyl. In some embodiments, R2Dmay be unsubstituted alkyl. In some embodiments, R2Dmay be substituted heteroalkyl. In some embodiments, R2Dmay be unsubstituted heteroalkyl. In some embodiments, R2Dmay be substituted cycloalkyl. In some embodiments, R2Dmay be unsubstituted cycloalkyl. In some embodiments, R2Dmay be substituted heterocycloalkyl. In some embodiments, R2Dmay be unsubstituted heterocycloalkyl. In some embodiments, R2Dmay be substituted aryl. In some embodiments, R2Dmay be unsubstituted aryl. In some embodiments, R2Dmay be substituted heteroaryl. In some embodiments, R2Dmay be unsubstituted heteroaryl.

[0166] In some embodiments, R2may be -SOv2NR2AR2B, wherein v2 may be an integer from 1 to 2 (e.g., -SONR2AR2B, -SO2NR2AR2B). In some embodiments, R2Amay be hydrogen. In some embodiments, R2Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Amay be -CX3. (e.g.. -CF3. -CCl₃, -CBr₃, -CI₃). In some embodiments, R2Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R2Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R2Amay be -COOH. In some embodiments, R2Amay be substituted alkyl. In some embodiments, R2Amay be unsubstituted alkyl. In some embodiments, R2Amay be substituted heteroalkyl. In some embodiments, R2Amay be unsubstituted heteroalkyl. In some embodiments, R2Amay be substituted cycloalkyl. In some embodiments, R2Amay be unsubstituted cycloalkyl. In some embodiments, R2Amay be substituted heterocycloalkyl. In some embodiments, R2Amay be unsubstituted heterocycloalkyl. In some embodiments, R2Amay be substituted aryl. In some embodiments,R2Amay be unsubstituted aryl. In some embodiments, R2Amay be substituted heteroaryl. In some embodiments, R2Amay be unsubstituted heteroaryl. In some embodiments, R2Bmay be hydrogen. In some embodiments, R2Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Bmay be -CX₃, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R2Bmay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R2Bmay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R2Bmay be -COOH. In some embodiments, R2Bmay be substituted alkyl. In some embodiments, R2Bmay be unsubstituted alkyl. In some embodiments, R2Bmay be substituted heteroalkyl. In some embodiments, R2Bmay be unsubstituted heteroalkyl. In some embodiments, R2Bmay be substituted cycloalkyl. In some embodiments, R2Bmay be unsubstituted cycloalkyl. In some embodiments, R2Bmay be substituted heterocycloalkyl. In some embodiments, R2Bmay be unsubstituted heterocycloalkyl. In some embodiments, R2Bmay be substituted aryl. In some embodiments, R2Bmay be unsubstituted aryl. In some embodiments, R2Bmay be substituted heteroaryl. In some embodiments, R2Bmay be unsubstituted heteroaryl.

[0167] In some embodiments, R2may be -NHC(O)NR2AR2B. In some embodiments, R2Amay be hydrogen. In some embodiments, R2Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R2Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr2, -CHI₂). In some embodiments, R2Amay be -CH2X, (e.g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments, R2Amay be -COOH. In some embodiments, R2Amay be substituted alkyl. In some embodiments, R2Amay be unsubstituted alkyl. In some embodiments, R2Amay be substituted heteroalkyl. In some embodiments, R2Amay be unsubstituted heteroalkyl. In some embodiments, R2Amay be substituted cycloalkyl. In some embodiments, R2Amay be unsubstituted cycloalkyl. In some embodiments, R2Amay be substituted heterocycloalkyl. In some embodiments, R2Amay be unsubstituted heterocycloalkyl. In some embodiments, R2Amay be substituted aryl. In some embodiments, R2Amay be unsubstituted aryl. In some embodiments, R2Amay be substituted heteroaryl. In some embodiments, R2Amay be unsubstituted heteroaryl. In some embodiments, R2Bmay be hydrogen. In some embodiments, R2Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Bmay be -CX3, (e.g., -CF₃, -CCl3, -CBr₃, -CI₃). In some embodiments, R2Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R2Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R2Bmay be -COOH. In some embodiments, R2Bmay be substituted alkyl. In some embodiments, R2Bmay be unsubstituted alkyl. In some embodiments, R2Bmay be substituted heteroalkyl. In some embodiments, R2Bmay be unsubstituted heteroalkyl. In someembodiments, R2Bmay be substituted cycloalkyl. In some embodiments, R2Bmay be unsubstituted cycloalkyl. In some embodiments, R2Bmay be substituted heterocycloalkyl. In some embodiments, R2Bmay be unsubstituted heterocycloalkyl. In some embodiments. R2Bmay be substituted aryl. In some embodiments, R2Bmay be unsubstituted aryl. In some embodiments, R2Bmay be substituted heteroaryl. In some embodiments, R2Bmay be unsubstituted heteroaryl.

[0168] In some embodiments, R2may be -N(O)m2, wherein m2 may be an integer from 1 to 2 (e.g., -N(O), -NO2).

[0169] In some embodiments, R2may be -NR2AR2B. In some embodiments, R2Amay be hydrogen. In some embodiments, R2Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R2Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI2). In some embodiments, R2Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R2Amay be -COOH. In some embodiments, R2Amay be substituted alkyl. In some embodiments, R2Amay be unsubstituted alkyl. In some embodiments, R2Amay be substituted heteroalkyl. In some embodiments, R2Amay be unsubstituted heteroalkyl. In some embodiments, R2Amay be substituted cycloalkyl. In some embodiments, R2Amay be unsubstituted cycloalkyl. In some embodiments, R2Amay be substituted heterocycloalkyl. In some embodiments, R2Amay be unsubstituted heterocycloalkyl. In some embodiments, R2Amay be substituted aryl. In some embodiments, R2Amay be unsubstituted aryl. In some embodiments, R2Amay be substituted heteroaryl. In some embodiments, R2Amay be unsubstituted heteroaryl. In some embodiments, R2Bmay be hydrogen. In some embodiments, R2Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Bmay be -CX3, (e.g., -CF₃, -CCl3, -CBr₃, -CI₃). In some embodiments, R2Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R2Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R2Dmay be -COOH. In some embodiments, R2Dmay be substituted alkyl. In some embodiments, R2Bmay be unsubstituted alkyl. In some embodiments, R2Bmay be substituted heteroalkyl. In some embodiments, R2Bmay be unsubstituted heteroalkyl. In some embodiments, R2Bmay be substituted cycloalkyl. In some embodiments, R2Bmay be unsubstituted cycloalkyl. In some embodiments. R2Bmay be substituted heterocycloalkyl. In some embodiments, R2Bmay be unsubstituted heterocycloalkyl. In some embodiments, R2Bmay be substituted aryl. In some embodiments, R2Bmay be unsubstituted aryl. In some embodiments, R2Bmay be substituted heteroaryl. In some embodiments, R2Bmay be unsubstituted heteroaryl.

[0170] In some embodiments, R2may be -C(O)R2C. In some embodiments, R2Cmay be hydrogen. In some embodiments, R2Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R2Cmay be -CHX2, (e g., -CHF2, -CHCk, -CHBr₂, -CHI₂). In some embodiments, R2Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R2Cmay be -COOH. In some embodiments, R2Cmay be substituted alkyl. In some embodiments, R2Cmay be unsubstituted alkyl. In some embodiments, R2Cmay be substituted heteroalkyl. In some embodiments, R2Cmay be unsubstituted heteroalkyl. In some embodiments, R2Cmay be substituted cycloalkyl. In some embodiments, R2Cmay be unsubstituted cycloalkyl. In some embodiments, R2Cmay be substituted heterocycloalkyl. In some embodiments, R2Cmay be unsubstituted heterocycloalkyl. In some embodiments, R2Cmay be substituted ai I. In some embodiments, R2Cmay be unsubstituted aryl. In some embodiments, R2Cmay be substituted heteroaryl. In some embodiments, R2Cmay be unsubstituted heteroaryl.

[0171] In some embodiments, R2may be -C(O)-OR2C. In some embodiments, R2Cmay be hydrogen. In some embodiments, R2Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R2Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R2Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R2Cmay be -COOH. In some embodiments, R2Cmay be substituted alkyl. In some embodiments, R2Cmay be unsubstituted alkyl. In some embodiments, R2Cmay be substituted heteroalkyl. In some embodiments, R2Cmay be unsubstituted heteroalkyl. In some embodiments, R2Cmay be substituted cycloalkyl. In some embodiments, R2Cmay be unsubstituted cycloalkyl. In some embodiments, R2Cmay be substituted heterocycloalkyl. In some embodiments, R2Cmay be unsubstituted heterocycloalkyl. In some embodiments, R2Cmay be substituted aryl. In some embodiments, R2Cmay be unsubstituted aryl. In some embodiments, R2Cmay be substituted heteroaryl. In some embodiments, R2Cmay be unsubstituted heteroaryl.

[0172] In some embodiments, R2may be -C(O)NR2AR2B. In some embodiments, R2Amay be hydrogen. In some embodiments, R2Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R2Amay be -CHX2. (e.g.. -CHF2. -CHCh, -CHBr2, -CHI₂). In some embodiments, R2Amay be -CH2X, (e.g., -CH2F, -CH₂Cl, -QhBr, -CH2I). In some embodiments, R2Amay be -COOH. In some embodiments, R2Amay be substituted alkyl. In some embodiments, R2Amay be unsubstituted alkyl. In some embodiments, R2Amay be substituted heteroalkyl. In some embodiments, R2Amay be unsubstituted heteroalkyl. In some embodiments, R2Amay besubstituted cycloalkyl. In some embodiments, R2Amay be unsubstituted cycloalkyl. In some embodiments, R2Amay be substituted heterocycloalkyl. In some embodiments, R2Amay be unsubstituted heterocycloalkyl. In some embodiments, R2Amay be substituted aryl. In some embodiments, R2Amay be unsubstituted aryl. In some embodiments, R2Amay be substituted heteroaryl. In some embodiments, R2Amay be unsubstituted heteroaryl. In some embodiments, R2Bmay be hydrogen. In some embodiments, R2Bmay be halogen, (e.g., -F, -Br, -Cl. -I). In some embodiments. R2Bmay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R2Bmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R2Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R2Bmay be -COOH. In some embodiments, R2Bmay be substituted alkyl. In some embodiments, R2Bmay be unsubstituted alkyl. In some embodiments. R2Bmay be substituted heteroalkyl. In some embodiments, R2Bmay be unsubstituted heteroalkyl. In some embodiments, R2Bmay be substituted cycloalkyl. In some embodiments, R2Bmay be unsubstituted cycloalkyl. In some embodiments, R2Bmay be substituted heterocycloalkyl. In some embodiments, R2Bmay be unsubstituted heterocycloalkyl. In some embodiments. R2Bmay be substituted aryl. In some embodiments, R2Dmay be unsubstituted aryl. In some embodiments, R2Bmay be substituted heteroaryl. In some embodiments, R2Bmay be unsubstituted heteroaryl.

[0173] In some embodiments, R2may be -OR2D. In some embodiments, R2Dmay be hydrogen. In some embodiments, R2Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Dmay be -CX3. (e.g.. -CF3. -CCl3, -CBr₃, -CI₃). In some embodiments, R2Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI2). In some embodiments, R2Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R2Dmay be -COOH. In some embodiments, R2Dmay be substituted alkyl. In some embodiments, R2Dmay be unsubstituted alkyl. In some embodiments, R2Dmay be substituted heteroalkyl. In some embodiments, R2Dmay be unsubstituted heteroalkyl. In some embodiments, R2Dmay be substituted cycloalkyl. In some embodiments, R2Dmay be unsubstituted cycloalkyl. In some embodiments, R2Dmay be substituted heterocycloalkyl. In some embodiments, R2Dmay be unsubstituted heterocycloalkyl. In some embodiments, R2Dmay be substituted aryl. In some embodiments, R2Dmay be unsubstituted aryl. In some embodiments, R2Dmay be substituted heteroaryl. In some embodiments, R2Dmay be unsubstituted heteroaryl.

[0174] In some embodiments, R2may be -NR2ASO2R2D. In some embodiments, R2Amay be hydrogen. In some embodiments, R2Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R2Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R2Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R2Amay be -COOH. In some embodiments, R2Amay be substituted alkyl. In some embodiments, R2Amay be unsubstituted alkyl. In some embodiments, R2Amay be substituted heteroalkyl. In some embodiments, R2Amay be unsubstituted heteroalkyl. In some embodiments, R2Amay be substituted cycloalkyl. In some embodiments, R2Amay be unsubstituted cycloalkyl. In some embodiments, R2Amay be substituted heterocycloalkyl. In some embodiments, R2Amay be unsubstituted heterocycloalkyl. In some embodiments, R2Amay be substituted aryl. In some embodiments, R2Amay be unsubstituted aryl. In some embodiments, R2Amay be substituted heteroaryl. In some embodiments, R2Amay be unsubstituted heteroaryl. In some embodiments, R2Dmay be hydrogen. In some embodiments, R2Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Dmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R2Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R2Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R2Dmay be -COOH. In some embodiments, R2Dmay be substituted alkyl. In some embodiments, R2Dmay be unsubstituted alkyl. In some embodiments, R2Dmay be substituted heteroalkyl. In some embodiments, R2Dmay be unsubstituted heteroalkyl. In some embodiments, R2Dmay be substituted cycloalkyl. In some embodiments, R2Dmay be unsubstituted cycloalkyl. In some embodiments, R2Dmay be substituted heterocycloalkyl. In some embodiments, R2Dmay be unsubstituted heterocycloalkyl. In some embodiments, R2Dmay be substituted aryl. In some embodiments, R2Dmay be unsubstituted aryl. In some embodiments, R2Dmay be substituted heteroaryl. In some embodiments, R2Dmay be unsubstituted heteroaryl.

[0175] In some embodiments, R2may be -NR2AC(O)R2C. In some embodiments, R2Amay be hydrogen. In some embodiments, R2Amay be halogen, (e.g., -F, -Br. -Cl, -I). In some embodiments, R2Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R2Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R2Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R2Amay be -COOH. In some embodiments, R2Amay be substituted alkyl. In some embodiments, R2Amay be unsubstituted alkyl. In some embodiments, R2Amay be substituted heteroalkyl. In some embodiments, R2Amay be unsubstituted heteroalkyl. In some embodiments, R2Amay be substituted cycloalkyl. In some embodiments, R2Amay be unsubstituted cycloalkyl. In some embodiments, R2Amay be substituted heterocycloalkyl. In some embodiments, R2Amay be unsubstituted heterocycloalkyl. In some embodiments, R2Amay be substituted aryl. In someembodiments, R2Amay be unsubstituted aryl. In some embodiments, R2Amay be substituted heteroaryl. In some embodiments, R2Amay be unsubstituted heteroaryl. In some embodiments, R2Cmay be hydrogen. In some embodiments, R2Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Cmay be -CX₃, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R2Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R2Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R2Cmay be -COOH. In some embodiments, R2Cmay be substituted alkyl. In some embodiments, R2Cmay be unsubstituted alkyl. In some embodiments, R2Cmay be substituted heteroalkyl. In some embodiments, R2Cmay be unsubstituted heteroalkyl. In some embodiments, R2Cmay be substituted cycloalkyl. In some embodiments, R2Cmay be unsubstituted cycloalkyl. In some embodiments, R2Cmay be substituted heterocycloalkyl. In some embodiments, R2Cmay be unsubstituted heterocycloalkyl. In some embodiments, R2Cmay be substituted aryl. In some embodiments, R2Cmay be unsubstituted aryl. In some embodiments, R2Cmay be substituted heteroaryl. In some embodiments, R2Cmay be unsubstituted heteroaryl.

[0176] In some embodiments, R2may be -NR2AC(O)OR2C. In some embodiments, R2Amay be hydrogen. In some embodiments, R2Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R2Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R2Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R2Amay be -COOH. In some embodiments, R2Amay be substituted alkyl. In some embodiments. R2Amay be unsubstituted alkyl. In some embodiments, R2Amay be substituted heteroalkyl. In some embodiments, R2Amay be unsubstituted heteroalkyl. In some embodiments, R2Amay be substituted cycloalkyl. In some embodiments, R2Amay be unsubstituted cycloalkyl. In some embodiments, R2Amay be substituted heterocycloalkyl. In some embodiments, R2Amay be unsubstituted heterocycloalkyl. In some embodiments, R2Amay be substituted aryl. In some embodiments, R2Amay be unsubstituted aryl. In some embodiments, R2Amay be substituted heteroaryl. In some embodiments, R2Amay be unsubstituted heteroaryl. In some embodiments, R2Cmay be hydrogen. In some embodiments, R2Cmay be halogen, (e.g.. -F, -Br, -Cl. -I). In some embodiments. R2Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R2Cmay' be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI2). In some embodiments, R2Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R2Cmay be -COOH. In some embodiments, R2Cmay be substituted alkyl. In some embodiments, R2Cmay be unsubstituted alkyl. In some embodiments. R2Cmay besubstituted heteroalkyl. In some embodiments, R2Cmay be unsubstituted heteroalkyl. In some embodiments, R2Cmay be substituted cycloalkyl. In some embodiments, R2Cmay be unsubstituted cycloalkyl. In some embodiments. R2Cmay be substituted heterocycloalkyl. In some embodiments, R2Cmay be unsubstituted heterocycloalkyl. In some embodiments, R2Cmay be substituted aryl. In some embodiments, R2Cmay be unsubstituted aryl. In some embodiments, R2Cmay be substituted heteroaryl. In some embodiments, R2Cmay be unsubstituted heteroaryl.

[0177] In some embodiments, R2may be -NR2AOR2C. In some embodiments, R2Amay be hydrogen. In some embodiments, R2Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R2Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R2Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R2Amay be -CH2X, (e g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments, R2Amay be -COOH. In some embodiments, R2Amay be substituted alkyl. In some embodiments, R2Amay be unsubstituted alkyl. In some embodiments, R2Amay be substituted heteroalkyl. In some embodiments, R2Amay be unsubstituted heteroalkyl. In some embodiments, R2Amay be substituted cycloalkyl. In some embodiments, R2Amay be unsubstituted cycloalkyl. In some embodiments, R2Amay be substituted heterocycloalkyl. In some embodiments, R2Amay be unsubstituted heterocycloalkyl. In some embodiments, R2Amay be substituted aryl. In some embodiments, R2Amay be unsubstituted aryl. In some embodiments, R2Amay be substituted heteroaryl. In some embodiments, R2Amay be unsubstituted heteroaryl. In some embodiments, R2Cmay be hydrogen. In some embodiments, R2Cmay be halogen, (e.g.. -F. -Br, -Cl, -I). In some embodiments, R2Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R2Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R2Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R2Cmay be -COOH. In some embodiments, R2Cmay be substituted alkyl. In some embodiments, R2Cmay be unsubstituted alkyl. In some embodiments, R2Cmay be substituted heteroalkyl. In some embodiments, R2Cmay be unsubstituted heteroalkyl. In some embodiments, R2Cmay be substituted cycloalkyl. In some embodiments, R2Cmay be unsubstituted cycloalkyl. In some embodiments, R2Cmay be substituted heterocycloalkyl. In some embodiments, R2Cmay be unsubstituted heterocycloalkyl. In some embodiments, R2Cmay be substituted aryl. In some embodiments, R2Cmay be unsubstituted aryl. In some embodiments, R2Cmay be substituted heteroaryl. In some embodiments, R2Cmay be unsubstituted heteroaryl.

[0178] In some embodiments, R2may be substituted alkyl. In some embodiments, R2may be unsubstituted alkyl. In some embodiments, R2may be substituted heteroalkyl. In some embodiments, R2may be unsubstituted heteroalkyl. In some embodiments, R2may be substituted cycloalkyl. In some embodiments, R2may be unsubstituted cycloalkyl. In some embodiments, R2may be substituted heterocycloalkyl. In some embodiments, R2may be unsubstituted heterocycloalkyl. In some embodiments, R2may be substituted aryl. In some embodiments, R2may be unsubstituted aryl. In some embodiments, R2may be substituted heteroaryl. In some embodiments, R2may be unsubstituted heteroaryl.

[0179] In some embodiments, R3may be absent. In some embodiments, R3may be hydrogen. In some embodiments, R3may be halogen. In some embodiments, R3may be -CX33, (e.g., CF3, CCI3, CBn, CI3). In some embodiments, R3may be -CHX32, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments. R3may be -CH2X3, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R3may be -OCX33, (e.g., -OCF3, -OCCI3, -OCBr₃, -OCI3). In some embodiments, R3may be -OCHX32, (e.g., -OCHF2, -OCHCI2, -OCHBr₂, -OCHI2). In some embodiments, R3may be -OCH2X3, (e g., -OCH2F, -OCH2CI, -OCH₂Br, -OCH2I). In some embodiments, R3may be -OCH3.

[0180] In some embodiments, R3may be -OCH2R3A. In some embodiments, R3Amay be hydrogen. In some embodiments, R3Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R3Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr2, -CHI2). In some embodiments, R3Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R3Amay be -COOH. In some embodiments, R3Amay be substituted alkyl. In some embodiments, R3Amay be unsubstituted alkyl. In some embodiments, R3Amay be substituted heteroalkyl. In some embodiments, R3Amay be unsubstituted heteroalkyl. In some embodiments, R3Amay be substituted cycloalkyl. In some embodiments, R3Amay be unsubstituted cycloalkyl. In some embodiments, R3Amay be substituted heterocycloalkyl. In some embodiments, R3Amay be unsubstituted heterocycloalkyl. In some embodiments, R3Amay be substituted aryl. In some embodiments, R3Amay be unsubstituted aryl. In some embodiments, R3Amay be substituted heteroaryl. In some embodiments, R3Amay be unsubstituted heteroaryl.

[0181] In some embodiments, R3may be -N₃, -CN.

[0182] In some embodiments, R3may be -SOn3R3Dwhereinn3 may be an integer from 0 - 4 (e.g., -S-, -SO-, -SO2-, -SO3-, -SO4-). In some embodiments, R3Dmay be hydrogen. In some embodiments, R3Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Dmay be-CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R3Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R3Dmay be -CH2X, (e.g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments, R3Dmay be -COOH. In some embodiments, R3Dmay be substituted alkyl. In some embodiments, R3Dmay be unsubstituted alkyl. In some embodiments, R3Dmay be substituted heteroalkyl. In some embodiments, R3Dmay be unsubstituted heteroalkyl. In some embodiments, R3Dmay be substituted cycloalkyl. In some embodiments, R3Dmay be unsubstituted cycloalkyl. In some embodiments. R3Dmay be substituted heterocycloalkyl. In some embodiments, R3Dmay be unsubstituted heterocycloalkyl. In some embodiments, R3Dmay be substituted aryl. In some embodiments, R3Dmay be unsubstituted aryl. In some embodiments, R3Dmay be substituted heteroaryl. In some embodiments, R3Dmay be unsubstituted heteroaryl.

[0183] In some embodiments, R3may be -SOv3NR3AR3BwhereinV3 may be an integer from 1 to 2 (e.g., -SON-, -SO2N-). In some embodiments, R3Amay be hydrogen. In some embodiments, R3Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R3Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R3Amay be -CH2X, (e.g., -CH2F, -CH₂Cl, -CH2Br, -CH2I). In some embodiments, R3Amay be -COOH. In some embodiments, R3Amay be substituted alkyl. In some embodiments, R3Amay be unsubstituted alkyl. In some embodiments, R3Amay be substituted heteroalkyl. In some embodiments, R3Amay be unsubstituted heteroalkyl. In some embodiments, R3Amay be substituted cycloalkyl. In some embodiments, R3Amay be unsubstituted cycloalkyl. In some embodiments. R3Amay be substituted heterocycloalkyl. In some embodiments, R3Amay be unsubstituted heterocycloalkyl. In some embodiments, R3Amay be substituted aryl. In some embodiments, R3Amay be unsubstituted aryl. In some embodiments, R3Amay be substituted heteroaryl. In some embodiments, R3Amay be unsubstituted heteroaryl. In some embodiments, R3Bmay be hydrogen. In some embodiments, R3Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Bmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R3Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R3Bmay be -CH2X, (e g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R3Bmay be -COOH. In some embodiments, R3Bmay be substituted alkyl. In some embodiments, R3Bmay be unsubstituted alkyl. In some embodiments, R3Bmay be substituted heteroalkyl. In some embodiments, R3Bmay be unsubstituted heteroalkyl. In some embodiments, R3Bmay be substituted cycloalkyl. In some embodiments, R3Bmay be unsubstituted cycloalkyl. In some embodiments, R3Bmay be substituted heterocycloalkyl. In some embodiments, R3Bmay beunsubstituted heterocycloalkyl. In some embodiments, R3Bmay be substituted aryl. In some embodiments, R3Bmay be unsubstituted aryl. In some embodiments, R'Bmay be substituted heteroaryl. In some embodiments, R3Bmay be unsubstituted heteroaryl.

[0184] In some embodiments, R3may be -NHC(O)NR3AR3B. In some embodiments, R3Amay be hydrogen. In some embodiments, R3Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R3Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI2). In some embodiments, R3Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R3Amay be -COOH. In some embodiments, R3Amay be substituted alkyl. In some embodiments, R3Amay be unsubstituted alkyl. In some embodiments, R3Amay be substituted heteroalkyl. In some embodiments, R3Amay be unsubstituted heteroalkyl. In some embodiments, R3Amay be substituted cycloalkyl. In some embodiments, R3Amay be unsubstituted cycloalkyl. In some embodiments, R3Amay be substituted heterocycloalkyl. In some embodiments, R3Amay be unsubstituted heterocycloalkyl. In some embodiments, R3Amay be substituted aryl. In some embodiments, R3Amay be unsubstituted aryl. In some embodiments, R3Amay be substituted heteroaryl. In some embodiments, R3Amay be unsubstituted heteroaryl. In some embodiments, R3Bmay be hydrogen. In some embodiments, R3Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Bmay be -CX3, (e.g., -CF₃, -CCl3, -CBr₃, -CI₃). In some embodiments, R3Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R3Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R3Dmay be -COOH. In some embodiments, R3Dmay be substituted alkyl. In some embodiments, R3Bmay be unsubstituted alkyl. In some embodiments, R3Bmay be substituted heteroalkyl. In some embodiments, R3Bmay be unsubstituted heteroalkyl. In some embodiments, R3Bmay be substituted cycloalkyl. In some embodiments, R'Bmay be unsubstituted cycloalkyl. In some embodiments. R3Bmay be substituted heterocycloalkyl. In some embodiments, R3Bmay be unsubstituted heterocycloalkyl. In some embodiments, R3Bmay be substituted aryl. In some embodiments, R3Bmay be unsubstituted aryl. In some embodiments, R3Bmay be substituted heteroaryl. In some embodiments, R3Bmay be unsubstituted heteroaryl.

[0185] In some embodiments, R3may be -N(0)m3 wherein m3 may be an integer from 1 to 2 (e.g., -N(O), -NO2).

[0186] In some embodiments, R3may be -NR3AR3B. In some embodiments, R3Amay be hydrogen. In some embodiments, R3Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R3Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R3Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R3Amay be -COOH. In some embodiments, R3Amay be substituted alkyl. In some embodiments, R3Amay be unsubstituted alkyl. In some embodiments, R3Amay be substituted heteroalkyl. In some embodiments, R3Amay be unsubstituted heteroalkyl. In some embodiments, R3Amay be substituted cycloalkyl. In some embodiments, R3Amay be unsubstituted cycloalkyl. In some embodiments, R3Amay be substituted heterocycloalkyl. In some embodiments, R3Amay be unsubstituted heterocycloalkyl. In some embodiments, R3Amay be substituted aryl. In some embodiments, R3Amay be unsubstituted aryl. In some embodiments, R3Amay be substituted heteroaryl. In some embodiments, R3Amay be unsubstituted heteroaryl. In some embodiments, R3Bmay be hydrogen. In some embodiments, R3Bmay be halogen, (e.g.. -F, -Br, -Cl, -I). In some embodiments, R3Bmay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R3Bmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R3Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R3Bmay be -COOH. In some embodiments, R3Bmay be substituted alkyl. In some embodiments, R3Bmay be unsubstituted alkyl. In some embodiments. R3Dmay be substituted heteroalkyl. In some embodiments, R3Bmay be unsubstituted heteroalkyl. In some embodiments, R3Bmay be substituted cycloalkyl. In some embodiments, R3Bmay be unsubstituted cycloalkyl. In some embodiments, R3Bmay be substituted heterocycloalkyl. In some embodiments, R3Bmay be unsubstituted heterocycloalkyl. In some embodiments. R3Bmay be substituted aryl. In some embodiments, R3Bmay be unsubstituted aryl. In some embodiments, R3Bmay be substituted heteroaryl. In some embodiments, R3Bmay be unsubstituted heteroaryl.

[0187] In some embodiments, R' may be -C(O)R?c. In some embodiments, R3Cmay be hydrogen. In some embodiments, R3Cmay be halogen, (e.g., -F. -Br, -Cl, -I). In some embodiments, R3Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R3Cmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI₂). In some embodiments, R3Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R3Cmay be -COOH. In some embodiments, R3Cmay be substituted alkyl. In some embodiments, R3Cmay be unsubstituted alkyl. In some embodiments, R3Cmay be substituted heteroalkyl. In some embodiments, R3Cmay be unsubstituted heteroalkyl. In some embodiments, R3Cmay be substituted cycloalkyl. In some embodiments, R3Cmay be unsubstituted cycloalkyl. In some embodiments, R?cmay be substituted heterocycloalkyl. In some embodiments, R3Cmay be unsubstituted heterocycloalkyl. In some embodiments, R3Cmay be substituted aryl. In someembodiments, R3Cmay be unsubstituted aryl. In some embodiments, R3Cmay be substituted heteroaryl. In some embodiments, R3Cmay be unsubstituted heteroaryl.

[0188] In some embodiments, R3may be -C(O)-OR3C. In some embodiments, R3Cmay be hydrogen. In some embodiments, R3Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R3Cmay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI2). In some embodiments, R3Cmay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R3Cmay be -COOH. In some embodiments, R3Cmay be substituted alkyl. In some embodiments, R3Cmay be unsubstituted alkyl. In some embodiments, R3Cmay be substituted heteroalkyl. In some embodiments, R3Cmay be unsubstituted heteroalkyl. In some embodiments, R3Cmay be substituted cycloalkyl. In some embodiments, R3Cmay be unsubstituted cycloalkyl. In some embodiments, R3Cmay be substituted heterocycloalkyl. In some embodiments, R3Cmay be unsubstituted heterocycloalkyl. In some embodiments, R3Cmay be substituted aryl. In some embodiments, R3Cmay be unsubstituted aryl. In some embodiments, R3Cmay be substituted heteroaryl. In some embodiments, R3Cmay be unsubstituted heteroaryl.

[0189] In some embodiments, R1may be -C(O)NR3AR3B. In some embodiments, R3Amay be hydrogen. In some embodiments, R3Amay be halogen, (e.g., -F, -Br. -Cl, -I). In some embodiments, R3Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R3Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R3Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R3Amay be -COOH. In some embodiments, R3Amay be substituted alkyl. In some embodiments, R3Amay be unsubstituted alkyl. In some embodiments, R3Amay be substituted heteroalkyl. In some embodiments, R3Amay be unsubstituted heteroalkyl. In some embodiments, R3Amay be substituted cycloalkyl. In some embodiments, R3Amay be unsubstituted cycloalkyl. In some embodiments, R3Amay be substituted heterocycloalkyl. In some embodiments, R3Amay be unsubstituted heterocycloalkyl. In some embodiments, R3Amay be substituted aryl. In some embodiments, R3Amay be unsubstituted aryl. In some embodiments, R3Amay be substituted heteroaryl. In some embodiments, R3Amay be unsubstituted heteroaryl. In some embodiments, R3Bmay be hydrogen. In some embodiments, R3Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Bmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R3Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R3Bmay be -CH2X, (e.g., -CH2F, -CH₂Cl, -CH2Br, -CH2I). In some embodiments, R3Bmay be -COOH. In some embodiments, R3Bmay be substituted alkyl. In some embodiments, R3Bmay be unsubstituted alkyl. In some embodiments. R3Bmay besubstituted heteroalkyl. In some embodiments, R3Bmay be unsubstituted heteroalkyl. In some embodiments, R3Bmay be substituted cycloalkyl. In some embodiments, R.'Hmay be unsubstituted cycloalkyl. In some embodiments. R3Bmay be substituted heterocycloalkyl. In some embodiments, R3Bmay be unsubstituted heterocycloalkyl. In some embodiments, R3Bmay be substituted aryl. In some embodiments, R3Bmay be unsubstituted aryl. In some embodiments, R3Bmay be substituted heteroaryl. In some embodiments, R3Bmay be unsubstituted heteroaryl.

[0190] In some embodiments, R3may be -OR3D. In some embodiments, R3Dmay be hydrogen. In some embodiments, R3Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Dmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R3Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R3Dmay be -CH2X, (e g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments, R3Dmay be -COOH. In some embodiments, R3Dmay be substituted alkyl. In some embodiments, R3Dmay be unsubstituted alkyl. In some embodiments, R3Dmay be substituted heteroalkyl. In some embodiments, R3Dmay be unsubstituted heteroalkyl. In some embodiments, R3Dmay be substituted cycloalkyl. In some embodiments, R5Dmay be unsubstituted cycloalkyl. In some embodiments, R5Dmay be substituted heterocycloalkyl. In some embodiments, R3Dmay be unsubstituted heterocycloalkyl. In some embodiments, R3Dmay be substituted aryl. In some embodiments, R3Dmay be unsubstituted aryl. In some embodiments, R3Dmay be substituted heteroaryl. In some embodiments, R3Dmay be unsubstituted heteroaryl.

[0191] In some embodiments, R3may be -NRJASO2RJD. In some embodiments, R3Amay be hydrogen. In some embodiments, R3Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R3Amay be -CHX2. (e.g.. -CHF2. -CHCh, -CHBr₂, -CHI2). In some embodiments, R3Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R’Amay be -COOH. In some embodiments, R3Amay be substituted alkyl. In some embodiments, R3Amay be unsubstituted alkyl. In some embodiments, R3Amay be substituted heteroalkyl. In some embodiments, R3Amay be unsubstituted heteroalkyl. In some embodiments, R3Amay be substituted cycloalkyl. In some embodiments, R3Amay be unsubstituted cycloalkyl. In some embodiments, R3Amay be substituted heterocycloalkyl. In some embodiments, R3Amay be unsubstituted heterocycloalkyl. In some embodiments, R3Amay be substituted aryl. In some embodiments, R3Amay be unsubstituted aryl. In some embodiments, R3Amay be substituted heteroaryl. In some embodiments, R3Amay be unsubstituted heteroaryl. In someembodiments, R3Dmay be hydrogen. In some embodiments, R3Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Dmay be -CX₃, (e g., -CF₃, -CCl₃, -CBr₃, -CI3). In some embodiments, R3Dmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R3Dmay be -CH2X, (e.g., -CFLF, -CH2CI, -CH2Br, -CH2I). In some embodiments, R3Dmay be -COOH. In some embodiments, R3Dmay be substituted alkyl. In some embodiments, R3Dmay be unsubstituted alkyl. In some embodiments, R3Dmay be substituted heteroalkyl. In some embodiments. R3Dmay be unsubstituted heteroalkyl. In some embodiments, R3Dmay be substituted cycloalkyl. In some embodiments, R5Dmay be unsubstituted cycloalkyl. In some embodiments, R5Dmay be substituted heterocycloalkyl. In some embodiments, R3Dmay be unsubstituted heterocycloalkyl. In some embodiments, R3Dmay be substituted aryl. In some embodiments, R3Dmay be unsubstituted aryl. In some embodiments, R3Dmay be substituted heteroaryl. In some embodiments, R3Dmay be unsubstituted heteroaryl.

[0192] In some embodiments, R3may be -NR3AC(O)R3C. In some embodiments, R3Amay be hydrogen. In some embodiments, R3Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R3Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R3Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R3Amay be -COOH. In some embodiments, R3Amay be substituted alkyl. In some embodiments. R3Amay be unsubstituted alkyl. In some embodiments, R3Amay be substituted heteroalkyl. In some embodiments, R3Amay be unsubstituted heteroalkyl. In some embodiments, R3Amay be substituted cycloalkyl. In some embodiments, R3Amay be unsubstituted cycloalkyl. In some embodiments, R3Amay be substituted heterocycloalkyl. In some embodiments, R3Amay be unsubstituted heterocycloalkyl.

[0193] In some embodiments, R3Amay be substituted aryl. In some embodiments, R3Amay be unsubstituted aryl. In some embodiments, R3Amay be substituted heteroaryl. In some embodiments, R3Amay be unsubstituted heteroaryl. In some embodiments, R3Cmay be hydrogen. In some embodiments, R3Cmay be halogen, (e.g.. -F, -Br, -Cl, -I). In some embodiments, R3Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R3Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHB12. -CHI₂). In some embodiments, R3Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R3Cmay be -COOH. In some embodiments, R3Cmay be substituted alkyl. In some embodiments, R3Cmay be unsubstituted alkyl. In some embodiments. R3Cmay be substituted heteroalkyl. In some embodiments, R3Cmay be unsubstituted heteroalkyl. In some embodiments, R3Cmay be substituted cycloalkyl. In some embodiments, R3Cmay beunsubstituted cycloalkyl. In some embodiments, R3Cmay be substituted heterocycloalkyl. In some embodiments, R3Cmay be unsubstituted helerocycloalkyl. In some embodiments. R3Cmay be substituted aryl. In some embodiments, R3Cmay be unsubstituted aryl. In some embodiments, R3Cmay be substituted heteroaryl. In some embodiments, R3Cmay be unsubstituted heteroaryl.

[0194] In some embodiments, FC may be -NR3AC(O)OR3C. In some embodiments, R3Amay be hydrogen. In some embodiments, R3Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R3Amay be -CHX2, (e g., -CHF2, -CHCI2, -CHBr₂, -CHI₂). In some embodiments, R3Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R3Amay be -COOH. In some embodiments, R3Amay be substituted alkyl. In some embodiments, R3Amay be unsubstituted alkyl. In some embodiments, R3Amay be substituted heteroalkyl. In some embodiments, R3Amay be unsubstituted heteroalkyl. In some embodiments, R3Amay be substituted cycloalkyl. In some embodiments, R3Amay be unsubstituted cycloalkyl. In some embodiments, R3Amay be substituted heterocycloalkyl. In some embodiments, R3Amay be unsubstituted heterocycloalkyl. In some embodiments, R3Amay be substituted aryl. In some embodiments, R3Amay be unsubstituted aryl. In some embodiments, R3Amay be substituted heteroaryl. In some embodiments, R3Amay be unsubstituted heteroaryl. In some embodiments, R3Cmay be hydrogen. In some embodiments, R3Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R3Cmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI₂). In some embodiments, R3Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R3Cmay be -COOH. In some embodiments, R3Cmay be substituted alkyl. In some embodiments, R?cmay be unsubstituted alkyl. In some embodiments, R3Cmay be substituted heteroalkyl. In some embodiments. R3Cmay be unsubstituted heteroalkyl. In some embodiments, R3Cmay be substituted cycloalkyl. In some embodiments, R3Cmay be unsubstituted cycloalkyl. In some embodiments, R3Cmay be substituted heterocycloalkyl. In some embodiments, R?cmay be unsubstituted heterocycloalkyl. In some embodiments, R3Cmay be substituted aryl. In some embodiments, R3Cmay be unsubstituted aryl. In some embodiments, R3Cmay be substituted heteroaryl. In some embodiments, R3Cmay be unsubstituted heteroaryl.

[0195] In some embodiments, R3may be -NR3AOR3C. In some embodiments, R3Amay be hydrogen. In some embodiments, R3Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R'may be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R3Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R3Amay be -COOH. In some embodiments, R3Amay be substituted alkyl. In some embodiments, R3Amay be unsubstituted alkyl. In some embodiments, R3Amay be substituted heteroalkyl. In some embodiments, R3Amay be unsubstituted heteroalkyl. In some embodiments, R3Amay be substituted cycloalkyl. In some embodiments, R3Amay be unsubstituted cycloalkyl. In some embodiments, R3Amay be substituted heterocycloalkyl. In some embodiments, R3Amay be unsubstituted heterocycloalkyl. In some embodiments, R3Amay be substituted aryl. In some embodiments, R3Amay be unsubstituted aryl. In some embodiments, R3Amay be substituted heteroaryl. In some embodiments, R3Amay be unsubstituted heteroaryl. In some embodiments, R3Cmay be hydrogen. In some embodiments, R3Cmay be halogen, (e.g.. -F, -Br, -Cl, -I). In some embodiments, R3Cmay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R3Cmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R3Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R3Cmay be -COOH. In some embodiments, R3Cmay be substituted alkyl. In some embodiments, R3Cmay be unsubstituted alkyl. In some embodiments. R3Cmay be substituted heteroalkyl. In some embodiments, R3Cmay be unsubstituted heteroalkyl. In some embodiments, R3Cmay be substituted cycloalkyl. In some embodiments, R3Cmay be unsubstituted cycloalkyl. In some embodiments, R3Cmay be substituted heterocycloalkyl. In some embodiments, R3Cmay be unsubstituted heterocycloalkyl. In some embodiments. R3Cmay be substituted aryl. In some embodiments, R3Cmay be unsubstituted aryl. In some embodiments, R3Cmay be substituted heteroaryl. In some embodiments, R3Cmay be unsubstituted heteroaryl.

[0196] In some embodiments, R' may be substituted alkyl. In some embodiments, R3may¬ be unsubstituted alkyl. In some embodiments, R3may be substituted heteroalkyl. In some embodiments, R3may be unsubstituted heteroalkyl. In some embodiments, R3may be substituted cycloalkyl. In some embodiments, R3may be unsubstituted cycloalkyl. In some embodiments, R3may be substituted heterocycloalkyl. In some embodiments, R3may be unsubstituted heterocycloalkyl. In some embodiments, R3may be substituted aryl. In some embodiments, R3may be unsubstituted aryl. In some embodiments, R3may be substituted heteroaryl. In some embodiments, R3may be unsubstituted heteroaryl.

[0197] In some embodiments, R4may be hydrogen. In some embodiments, R4may be halogen. In some embodiments, R4may be -CX43, (e.g., CF3, CCI3, CBn, CI3). In some embodiments, R4may be -CHX42, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI₂). In someembodiments, R4may be -CH2X4, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R4may be -OCX43, (e.g., -OCF3, -OCCh. -OCBrs, -OCI3). In some embodiments, R4may be -OCHX42, (e.g., -OCHF2, -OCHCh, -OCHBr2, -OCHh). In some embodiments, R4may be -OCH2X4, (e.g., -OCH2F, -OCH2CI, -OCFBBr, -OCH2I). In some embodiments, R4may be -OCHs.

[0198] In some embodiments, R4may be -OCH2R4A. In some embodiments, R4Amay be hydrogen. In some embodiments, R4Amay be halogen, (e.g., -F. -Br, -Cl, -I). In some embodiments, R4Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R4Amay be -CHX2, (e g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R4Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R4Amay be -COOH. In some embodiments, R4Amay be substituted alkyl. In some embodiments, R4Amay be unsubstituted alkyl. In some embodiments, R4Amay be substituted heteroalkyl. In some embodiments, R4Amay be unsubstituted heteroalkyl. In some embodiments, R4Amay be substituted cycloalkyl. In some embodiments, R4Amay be unsubstituted cycloalkyl. In some embodiments, R4Amay be substituted heterocycloalkyl. In some embodiments, R4Amay be unsubstituted heterocycloalkyl. In some embodiments, R4Amay be substituted aryl. In some embodiments, R4Amay be unsubstituted aryl. In some embodiments, R4Amay be substituted heteroaryl. In some embodiments, R4Amay be unsubstituted heteroaryl.

[0199] In some embodiments, R4may be -N3, -CN.

[0200] In some embodiments, R4may be -SOn4R4Dwhereinn4 may be an integer from 0 - 4 (e.g., -S-, -SO-, -SO2-, -SO3-, -SO4-). In some embodiments, R4Dmay be hydrogen. In some embodiments, R4Dmay be halogen, (e.g., -F. -Br, -Cl, -I). In some embodiments, R4Dmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R4Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R4Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R4Dmay be -COOH. In some embodiments, R4Dmay be substituted alkyl. In some embodiments, R4Dmay be unsubstituted alkyl. In some embodiments, R4Dmay be substituted heteroalkyl. In some embodiments, R4Dmay be unsubstituted heteroalkyl. In some embodiments, R4Dmay be substituted cycloalkyl. In some embodiments, R4Dmay be unsubstituted cycloalkyl. In some embodiments, R4Dmay be substituted heterocycloalkyl. In some embodiments, R4Dmay be unsubstituted heterocycloalkyl. In some embodiments. R4Dmay be substituted aryl. In some embodiments. R4Dmay be unsubstituted aryl. In some embodiments, R4Dmay be substituted heteroaryl. In some embodiments, R4Dmay be unsubstituted heteroaryl.

[0201] In some embodiments, R4may be -SOv4NR4AR4Bwherein v4 may be an integer from 1 to 2 (e.g., -SON-, -SO2N-). In some embodiments, R4Amay be hydrogen. In some embodiments, R4Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R4Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R4Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R4Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R4Amay be -COOH. In some embodiments, R4Amay be substituted alkyl. In some embodiments, R4Amay be unsubstituted alkyl. In some embodiments, R4Amay be substituted heteroalkyl. In some embodiments, R4Amay be unsubstituted heteroalkyl. In some embodiments, R4Amay be substituted cycloalkyl. In some embodiments, R4Amay be unsubstituted cycloalkyl. In some embodiments, R4Amay be substituted heterocycloalkyl. In some embodiments, R4Amay be unsubstituted heterocycloalkyl. In some embodiments, R4Amay be substituted aryl. In some embodiments, R4Amay be unsubstituted aryl. In some embodiments, R4Amay be substituted heteroaryl. In some embodiments, R4Amay be unsubstituted heteroaryl. In some embodiments, R4Bmay be hydrogen. In some embodiments, R4Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R4Dmay be -CX3. (e.g., -CF3. -CCl₃, -CBr₃, -CI₃). In some embodiments, R4Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI₂). In some embodiments, R4Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R4Bmay be -COOH. In some embodiments, R4Bmay be substituted alkyl. In some embodiments, R4Bmay be unsubstituted alkyl. In some embodiments, R4Bmay be substituted heteroalkyl. In some embodiments, R4Bmay be unsubstituted heteroalkyl. In some embodiments, R4Bmay be substituted cycloalkyl. In some embodiments, R4Bmay be unsubstituted cycloalkyl. In some embodiments, R4Bmay be substituted heterocycloalkyl. In some embodiments, R4Bmay be unsubstituted heterocycloalkyl. In some embodiments, R4Bmay be substituted aryl. In some embodiments, R4Bmay be unsubstituted aryl. In some embodiments, R4Bmay be substituted heteroaryl. In some embodiments, R4Bmay be unsubstituted heteroaryl.

[0202] In some embodiments, R4may be -NHC(O)NR4AR4B. In some embodiments, R4Amay be hydrogen. In some embodiments, R4Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R4Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R4Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R4Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R4Amay be -COOH. In some embodiments, R4Amay be substituted alkyl. In some embodiments, R4Amay be unsubstituted alkyl. In some embodiments, R4Amay be substituted heteroalkyl. In some embodiments, R4Amay be unsubstituted heteroalkyl. In some embodiments, R4Amay besubstituted cycloalkyl. In some embodiments, R4Amay be unsubstituted cycloalkyl. In some embodiments, R4Amay be substituted heterocycloalkyl. In some embodiments, R4Amay be unsubstituted heterocycloalkyl. In some embodiments, R4Amay be substituted aryl. In some embodiments, R4Amay be unsubstituted aryl. In some embodiments, R4Amay be substituted heteroaryl. In some embodiments, R4Amay be unsubstituted heteroaryl. In some embodiments, R4Bmay be hydrogen. In some embodiments, R4Bmay be halogen, (e.g., -F, -Br, -Cl. -I). In some embodiments. R4Bmay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R4Bmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R4Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R4Bmay be -COOH. In some embodiments, R4Bmay be substituted alkyl. In some embodiments, R4Bmay be unsubstituted alkyl. In some embodiments. R4Bmay be substituted heteroalkyl. In some embodiments, R4Bmay be unsubstituted heteroalkyl. In some embodiments, R4Bmay be substituted cycloalkyl. In some embodiments, R4Bmay be unsubstituted cycloalkyl. In some embodiments, R4Bmay be substituted heterocycloalkyl. In some embodiments, R4Bmay be unsubstituted heterocycloalkyl. In some embodiments. R4Bmay be substituted aryl. In some embodiments, R4Dmay be unsubstituted aryl. In some embodiments, R4Bmay be substituted heteroaryl. In some embodiments, R4Bmay be unsubstituted heteroaryl.

[0203] In some embodiments, R4may be -N(0)m4 whereinm4 may be an integer from 1 to 2 (e.g., -N(O), -NO2).

[0204] In some embodiments, R4may be -NR4AR4B. In some embodiments, R4Amay be hydrogen. In some embodiments, R4Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R4Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R4Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R4Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R4Amay be -COOH. In some embodiments, R4Amay be substituted alkyl. In some embodiments. R4Amay be unsubstituted alkyl. In some embodiments, R4Amay be substituted heteroalkyl. In some embodiments, R4Amay be unsubstituted heteroalkyl. In some embodiments, R4Amay be substituted cycloalkyl. In some embodiments, R4Amay be unsubstituted cycloalkyl. In some embodiments, R4Amay be substituted heterocycloalkyl. In some embodiments, R4Amay be unsubstituted heterocycloalkyl. In some embodiments, R4Amay be substituted aryl. In some embodiments, R4Amay be unsubstituted aryl. In some embodiments, R4Amay be substituted heteroaryl. In some embodiments, R4Amay be unsubstituted heteroaryl. In some embodiments, R4Bmay be hydrogen. In some embodiments, R4Bmay be halogen, (e.g.. -F, -Br, -Cl, -I). In some embodiments, R4Bmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R4Bmay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI2). In some embodiments, R4Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R4Bmay be -COOH. In some embodiments, R4Bmay be substituted alkyl. In some embodiments, R4Bmay be unsubstituted alkyl. In some embodiments, R4Bmay be substituted heteroalkyl. In some embodiments. R4Bmay be unsubstituted heteroalkyl. In some embodiments, R4Bmay be substituted cycloalkyl. In some embodiments, R4Bmay’ be unsubstituted cycloalkyl. In some embodiments, R4Bmay be substituted heterocycloalkyl. In some embodiments, R4Bmay be unsubstituted heterocycloalkyl. In some embodiments, R4Bmay be substituted aryl. In some embodiments, R4Bmay be unsubstituted aryl. In some embodiments, R4Bmay be substituted heteroaryl. In some embodiments, R4Bmay be unsubstituted heteroaryl.

[0205] In some embodiments, R4may be -C(O)R4C. In some embodiments, R4Cmay be hydrogen. In some embodiments, R4Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R4Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R4Cmay be -CHX2. (e.g., -CHF2, -CHCl₂, -CHBr2, -CHI2). In some embodiments, R4Cmay be -CH2X, (e g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments. R4Cmay be -COOH. In some embodiments, R4Cmay be substituted alkyl. In some embodiments, R4Cmay be unsubstituted alkyl. In some embodiments, R4Cmay be substituted heteroalkyl. In some embodiments, R4Cmay be unsubstituted heteroalkyl. In some embodiments, R4Cmay be substituted cycloalkyl. In some embodiments, R4Cmay be unsubstituted cycloalkyl. In some embodiments, R4Cmay be substituted heterocycloalkyl. In some embodiments, R4Cmay be unsubstituted heterocycloalkyl. In some embodiments, R4Cmay be substituted aryl. In some embodiments, R4Cmay be unsubstituted aryl. In some embodiments, R4Cmay be substituted heteroaryl. In some embodiments, R4Cmay be unsubstituted heteroaryl.

[0206] In some embodiments, R4may be -C(O)-OR4C. In some embodiments, R4Cmay be hydrogen. In some embodiments, R4Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R4Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R4Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R4Cmay be -CH2X, (e.g., -CH2F, -CH₂Cl, -CH2Br, -CH2I). In some embodiments, R4Cmay be -COOH. In some embodiments, R4Cmay be substituted alkyl. In some embodiments, R4Cmay be unsubstituted alkyl. In some embodiments, R4Cmay be substituted heteroalkyl. In some embodiments, R4Cmay be unsubstituted heteroalkyl. In some embodiments, R4Cmay be substituted cycloalkyl. In some embodiments, R4Cmay be unsubstituted cycloalkyl. In someembodiments, R4Cmay be substituted heterocycloalkyl. In some embodiments, R4Cmay be unsubstituted heterocycloalkyl. In some embodiments, R4Cmay be substituted aryl. In some embodiments, R4Cmay be unsubstituted aryl. In some embodiments, R4Cmay be substituted heteroaryl. In some embodiments, R4Cmay be unsubstituted heteroaryl.

[0207] In some embodiments, R4may be -C(O)NR4AR4B. In some embodiments, R4Amay be hydrogen. In some embodiments, R4Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R4Amay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R4Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R4Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R4Amay be -COOH. In some embodiments, R4Amay be substituted alkyl. In some embodiments, R4Amay be unsubstituted alkyl. In some embodiments, R4Amay be substituted heteroalkyl. In some embodiments, R4Amay be unsubstituted heteroalkyl. In some embodiments, R4Amay be substituted cycloalkyl. In some embodiments, R4Amay be unsubstituted cycloalkyl. In some embodiments, R4Amay be substituted heterocycloalkyl. In some embodiments, R4Amay be unsubstituted heterocycloalkyl. In some embodiments, R4Amay be substituted aryl. In some embodiments, R4Amay be unsubstituted aryl. In some embodiments, R4Amay be substituted heteroaryl. In some embodiments, R4Amay be unsubstituted heteroaryl. In some embodiments, R4Bmay be hydrogen. In some embodiments, R4Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R4Bmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R4Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R4Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br. -CH2I). In some embodiments, R4Bmay be -COOH. In some embodiments, R4Bmay be substituted alkyl. In some embodiments, R4Bmay be unsubstituted alkyl. In some embodiments, R4Bmay be substituted heteroalkyl. In some embodiments, R4Bmay be unsubstituted heteroalkyl. In some embodiments, R4Bmay be substituted cycloalkyl. In some embodiments, R4Bmay be unsubstituted cycloalkyl. In some embodiments, R4Bmay be substituted heterocycloalkyl. In some embodiments, R4Bmay be unsubstituted heterocycloalkyl. In some embodiments, R4Bmay be substituted aryl. In some embodiments, R4Bmay be unsubstituted aryl. In some embodiments, R4Bmay be substituted heteroaryl. In some embodiments, R4Bmay be unsubstituted heteroaryl.

[0208] In some embodiments, R4may be -OR4D. In some embodiments, R4Dmay be hydrogen. In some embodiments, R4Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R4Dmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R4Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI₂). In some embodiments, R4Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R4Dmay be -COOH. In some embodiments, R4Dmay be substituted alkyl. In some embodiments, R4Dmay be unsubstituted alkyl. In some embodiments, R4Dmay be substituted heteroalkyl. In some embodiments, R4Dmay be unsubstituted heteroalkyl. In some embodiments, R4Dmay be substituted cycloalkyl. In some embodiments, R4Dmay be unsubstituted cycloalkyl. In some embodiments, R4Dmay be substituted heterocycloalkyl. In some embodiments, R4Dmay be unsubstituted heterocycloalkyl. In some embodiments, R4Dmay be substituted aryl. In some embodiments, R4Dmay be unsubstituted aryl. In some embodiments, R4Dmay be substituted heteroaryl. In some embodiments, R4Dmay be unsubstituted heteroaryl.

[0209] In some embodiments, R4may be -NR4ASO2R4D. In some embodiments, R4Amay be hydrogen. In some embodiments, R4Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R4Amay be -CX3. (e.g., -CF3. -CCl3, -CBr₃, -CI₃). In some embodiments, R4Amay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R4Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R4Amay be -COOH. In some embodiments, R4Amay be substituted alkyl. In some embodiments, R4Amay be unsubstituted alkyl. In some embodiments, R4Amay be substituted heteroalkyl. In some embodiments, R4Amay be unsubstituted heteroalkyl. In some embodiments, R4Amay be substituted cycloalkyl. In some embodiments, R4Amay be unsubstituted cycloalkyl. In some embodiments, R4Amay be substituted heterocycloalkyl. In some embodiments, R4Amay be unsubstituted heterocycloalkyl. In some embodiments, R4Amay be substituted aryl. In some embodiments, R4Amay be unsubstituted aryl. In some embodiments, R4Amay be substituted heteroaryl. In some embodiments, R4Amay be unsubstituted heteroaryl. In some embodiments, R4Dmay be hydrogen. In some embodiments, R4Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R4Dmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R4Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R4Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R4Dmay be -COOH. In some embodiments, R4Dmay be substituted alkyl. In some embodiments, R4Dmay be unsubstituted alkyl. In some embodiments, R4Dmay be substituted heteroalkyl. In some embodiments. R4Dmay be unsubstituted heteroalkyl. In some embodiments, R4Dmay be substituted cycloalkyl. In some embodiments, R4Dmay be unsubstituted cycloalkyl. In some embodiments, R4Dmay be substituted heterocycloalkyl. In some embodiments, R4Dmay be unsubstituted heterocycloalkyl. In some embodiments, R4Dmay be substituted aryl. In some embodiments, R4Dmay be unsubstituted aryl. In someembodiments, R4Dmay be substituted heteroaryl. In some embodiments, R4Dmay be unsubstituted heteroaryl.

[0210] In some embodiments, R4may be -NR4AC(O)R4C. In some embodiments, R4Amay be hydrogen. In some embodiments, R4Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R4Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R4Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R4Amay be -CH2X, (e g., -CH2F, -CH2CI, -C BBr, -CH2I). In some embodiments, R4Amay be -COOH. In some embodiments, R4Amay be substituted alkyl. In some embodiments, R4Amay be unsubstituted alkyl. In some embodiments, R4Amay be substituted heteroalkyl. In some embodiments, R4Amay be unsubstituted heteroalkyl. In some embodiments, R4Amay be substituted cycloalkyl. In some embodiments, R4Amay be unsubstituted cycloalkyl. In some embodiments, R4Amay be substituted heterocycloalkyl. In some embodiments, R4Amay be unsubstituted heterocycloalkyl. In some embodiments, R4Amay be substituted aryl. In some embodiments, R4Amay be unsubstituted aryl. In some embodiments, R4Amay be substituted heteroaryl. In some embodiments, R4Amay be unsubstituted heteroaryl. In some embodiments, R4Cmay be hydrogen. In some embodiments, R4Cmay be halogen, (e.g.. -F, -Br, -Cl, -I). In some embodiments, R4Cmay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R4Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI2). In some embodiments, R4Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R4Cmay be -COOH. In some embodiments, R4Cmay be substituted alkyl. In some embodiments, R4Cmay be unsubstituted alkyl. In some embodiments. R4Cmay be substituted heteroalkyl. In some embodiments, R4Cmay be unsubstituted heteroalkyl. In some embodiments, R4Cmay be substituted cycloalkyl. In some embodiments, R4Cmay be unsubstituted cycloalkyl. In some embodiments, R4Cmay be substituted heterocycloalkyl. In some embodiments, R4Cmay be unsubstituted heterocycloalkyl. In some embodiments. R4Cmay be substituted aryl. In some embodiments, R4Cmay be unsubstituted aryl. In some embodiments, R4Cmay be substituted heteroaryl. In some embodiments, R4Cmay be unsubstituted heteroaryl.

[0211] In some embodiments, R4may be -NR4AC(O)OR4C. In some embodiments, R4Amay be hydrogen. In some embodiments, R4Amay be halogen, (e.g., -F, -Br. -Cl, -I). In some embodiments, R4Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R4Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R4Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R4Amay be -COOH. In some embodiments, R4Amay be substituted alkyl. In some embodiments, R4Amay beunsubstituted alkyl. In some embodiments, R4Amay be substituted heteroalkyl. In some embodiments, R4Amay be unsubstituted heteroalkyl. In some embodiments, R4Amay be substituted cycloalkyl. In some embodiments, R4Amay be unsubstituted cycloalkyl. In some embodiments, R4Amay be substituted heterocycloalkyl. In some embodiments, R4Amay be unsubstituted heterocycloalkyl. In some embodiments, R4Amay be substituted aryl. In some embodiments, R4Amay be unsubstituted aryl. In some embodiments, R4Amay be substituted heteroaryl. In some embodiments, R4Amay be unsubstituted heteroaryl. In some embodiments, R4Cmay be hydrogen. In some embodiments, R4Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R4Cmay be -CX₃, (e.g., -CF₃, -CCl₃, -CBr₃, -CI3). In some embodiments, R4Cmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R4Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R4Cmay be -COOH. In some embodiments, R4Cmay be substituted alkyl. In some embodiments, R4Cmay be unsubstituted alkyl. In some embodiments, R4Cmay be substituted heteroalkyl. In some embodiments, R4Cmay be unsubstituted heteroalkyl. In some embodiments, R4Cmay be substituted cycloalkyl. In some embodiments, R4Cmay be unsubstituted cycloalkyl. In some embodiments. R4Cmay be substituted heterocycloalkyl. In some embodiments, R4Cmay be unsubstituted heterocycloalkyl. In some embodiments, R4Cmay be substituted aryl. In some embodiments, R4Cmay be unsubstituted aryl. In some embodiments, R4Cmay be substituted heteroaryl. In some embodiments, R4Cmay be unsubstituted heteroaryl.

[0212] In some embodiments, R4may be -NR4AOR4C. In some embodiments. R4Amay be hydrogen. In some embodiments, R4Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R4Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R4Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R4Amay be -CH2X, (e g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments, R4Amay be -COOH. In some embodiments, R4Amay be substituted alkyl. In some embodiments, R4Amay be unsubstituted alkyl. In some embodiments, R4Amay be substituted heteroalkyl. In some embodiments, R4Amay be unsubstituted heteroalkyl. In some embodiments, R4Amay be substituted cycloalkyl. In some embodiments, R4Amay be unsubstituted cycloalkyl. In some embodiments, R4Amay be substituted heterocycloalkyl. In some embodiments, R4Amay be unsubstituted heterocycloalkyl. In some embodiments, R4Amay be substituted aryl. In some embodiments, R4Amay be unsubstituted aryl. In some embodiments, R4Amay be substituted heteroaryl. In some embodiments, R4Amay be unsubstituted heteroaryl. In some embodiments, R4Cmay be hydrogen. In some embodiments, R4Cmay be halogen, (e.g.. -F, -Br, -Cl, -I). In some embodiments, R4Cmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R4Cmay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI2). In some embodiments, R4Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R4Cmay be -COOH. In some embodiments, R4Cmay be substituted alkyl. In some embodiments, R4Cmay be unsubstituted alkyl. In some embodiments, R4Cmay be substituted heteroalkyl. In some embodiments. R4Cmay be unsubstituted heteroalkyl. In some embodiments, R4Cmay be substituted cycloalkyl. In some embodiments, R4Cmay’ be unsubstituted cycloalkyl. In some embodiments, R4Cmay be substituted heterocycloalkyl. In some embodiments, R4Cmay be unsubstituted heterocycloalkyl. In some embodiments, R4Cmay be substituted aryl. In some embodiments, R4Cmay be unsubstituted aryl. In some embodiments, R4Cmay be substituted heteroaryl. In some embodiments, R4Cmay be unsubstituted heteroaryl.

[0213] In some embodiments, R4may be substituted alkyl. In some embodiments, R4may be unsubstituted alkyl. In some embodiments, R4may be substituted heteroalkyl. In some embodiments, R4may be unsubstituted heteroalkyl. In some embodiments, R4may be substituted cycloalkyl. In some embodiments, R4may be unsubstituted cycloalkyl. In some embodiments, R4may be substituted heterocycloalkyl. In some embodiments, R4may be unsubstituted heterocycloalkyl. In some embodiments, R4may be substituted aryl. In some embodiments, R4may be unsubstituted aryl. In some embodiments, R4may be substituted heteroaryl. In some embodiments, R4may be unsubstituted heteroaryl.

[0214] In some embodiments, R5may be hydrogen. In some embodiments, R5may be halogen. In some embodiments, R5may be -CX53, (e.g., CF3, CCI3, CBn, CI3). In some embodiments, R5may be -CHX52, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R5may be -CH2X3, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R5may be -OCX53, (e.g., -OCF3, -OCCI3, -OCBr3, -OCI3). In some embodiments, R5may be -OCHX52, (e.g., -OCHF2, -OCHCh. -OCHBr2, -OCHI2). In some embodiments, R5may be -OCH2X5, (e.g., -OCH2F, -OCH2CI, -OCFBBr, -OCH2I). In some embodiments, R5may be -OCHs

[0215] In some embodiments R5may be -OCH2R5A. In some embodiments, R5Amay be hydrogen. In some embodiments, R5Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R5 Amay be -CX3. (e.g.. -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R5Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI2). In some embodiments, R5Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R5Amay be -COOH. In some embodiments, R5Amay be substituted alkyl. In some embodiments, R5Amay beunsubstituted alkyl. In some embodiments, R3Amay be substituted heteroalkyl. In some embodiments, R3Amay be unsubstituted heteroalkyl. In some embodiments, R5Amay be substituted cycloalkyl. In some embodiments, R5Amay be unsubstituted cycloalkyl. In some embodiments, R3Amay be substituted heterocycloalkyl. In some embodiments, R3Amay be unsubstituted heterocycloalkyl. In some embodiments, R3Amay be substituted aryl. In some embodiments, R3Amay be unsubstituted aryl. In some embodiments, R5Amay be substituted heteroaryl. In some embodiments, R3Amay be unsubstituted heteroaryl.

[0216] In some embodiments R5may be -N₃, -CN.

[0217] In some embodiments R3may be -SOn5R3Dwhereinns may be an integer from 0 - 4 (e.g., -S-, -SO-, -SO2-, -SO3-, -SO4-). In some embodiments, R5Dmay be hydrogen. In some embodiments, R5Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R’Dmay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R3Dmay be -CHX2. (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R5Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R5Dmay be -COOH. In some embodiments, R5Dmay be substituted alkyl. In some embodiments, R5Dmay be unsubstituted alkyl. In some embodiments, R3Dmay be substituted heteroalkyl. In some embodiments, R3Dmay be unsubstituted heteroalkyl. In some embodiments, R5Dmay be substituted cycloalkyl. In some embodiments, R3Dmay be unsubstituted cycloalkyl. In some embodiments, R3Dmay be substituted heterocycloalky 1. In some embodiments, R3Dmay be unsubstituted heterocycloalkyl. In some embodiments, R5Dmay be substituted aryl. In some embodiments, R5Dmay be unsubstituted aryl. In some embodiments, R5Dmay be substituted heteroaryl. In some embodiments, R3Dmay be unsubstituted heteroaryl.

[0218] In some embodiments R3may be -SOv5NR3AR3BwhereinV5 may be an integer from 1 to 2 (e.g., -SON-, -SO2N-). In some embodiments, R3Amay be hydrogen. In some embodiments, R3Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R5Amay be -CX3, (e.g., -CF3. -CCl3, -CBr₃, -CI₃). In some embodiments, R3Amay be -CHX2. (e.g.. -CHF2, -CHCh. -CHBr2, -CHI2). In some embodiments. R3Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R3Amay be -COOH. In some embodiments, R3Amay be substituted alkyl. In some embodiments, R3Amay be unsubstituted alkyl. In some embodiments, R3Amay be substituted heteroalkyl. In some embodiments, R3Amay be unsubstituted heteroalkyl. In some embodiments, R3Amay be substituted cycloalkyl. In some embodiments, R3Amay be unsubstituted cycloalkyl. In some embodiments, R3Amay be substituted heterocycloalkyl. In some embodiments, R3Amay be unsubstituted heterocycloalkyl. In some embodiments, R3Amay be substituted aryl. In some embodiments,R5Amay be unsubstituted aryl. In some embodiments, R5Amay be substituted heteroaryl. In some embodiments, R5Amay be unsubstituted heteroaryl. In some embodiments, R5Bmay be hydrogen. In some embodiments, R5Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R5Bmay be -CX₃, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R5Bmay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R5Bmay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R5Bmay be -COOH. In some embodiments, R5Bmay be substituted alkyl. In some embodiments, R5Bmay be unsubstituted alkyl. In some embodiments, R5Bmay be substituted heteroalkyl. In some embodiments, R5Bmay be unsubstituted heteroalkyl. In some embodiments, R5Bmay be substituted cycloalkyl. In some embodiments, R5Bmay be unsubstituted cycloalkyl. In some embodiments, R5Bmay be substituted heterocycloalkyl. In some embodiments, R5Bmay be unsubstituted heterocycloalkyl. In some embodiments, R5Bmay be substituted aryl. In some embodiments, R5Bmay be unsubstituted aryl. In some embodiments, R5Bmay be substituted heteroaryl. In some embodiments, R5Bmay be unsubstituted heteroaryl.

[0219] In some embodiments R5may be -NHC(O)NR5AR3B. In some embodiments, R5Amay be hydrogen. In some embodiments, R5Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R5Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R5Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R5Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R5Amay be -COOH. In some embodiments, R5Amay be substituted alkyl. In some embodiments, R5Amay be unsubstituted alkyl. In some embodiments, R5Amay be substituted heteroalkyl. In some embodiments, R5Amay be unsubstituted heteroalkyl. In some embodiments, R5Amay be substituted cycloalkyl. In some embodiments, R5Amay be unsubstituted cycloalkyl. In some embodiments, R5Amay be substituted heterocycloalkyl. In some embodiments, R5Amay be unsubstituted heterocycloalkyl. In some embodiments, R5Amay be substituted aryl. In some embodiments, R3Amay be unsubstituted aryl. In some embodiments, R5Amay be substituted heteroaryl. In some embodiments, R5Amay be unsubstituted heteroaryl. In some embodiments, R5Bmay be hydrogen. In some embodiments, R5Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R5Bmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI3). In some embodiments, R5Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R5Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R5Bmay be -COOH. In some embodiments, R5Bmay be substituted alkyl. In some embodiments, R5Bmay be unsubstituted alkyl. In some embodiments, R5Bmay be substituted heteroalkyl. In some embodiments. R5Bmay be unsubstituted heteroalkyl. In someembodiments, R5Bmay be substituted cycloalkyl. In some embodiments, R5Bmay be unsubstituted cycloalkyl. In some embodiments, R5Bmay be substituted heterocycloalkyl. In some embodiments, R5Bmay be unsubstituted heterocycloalkyl. In some embodiments. R5Bmay be substituted aryl. In some embodiments, R5Bmay be unsubstituted aryl. In some embodiments, R5Bmay be substituted heteroaryl. In some embodiments, R5Bmay be unsubstituted heteroaryl.

[0220] In some embodiments R5may be -N(O)m5wherein m5 may be an integer from 1 to 2 (e.g., -N(O), -NO2).

[0221] In some embodiments R3may be -NR3AR3B. In some embodiments, R3Amay be hydrogen. In some embodiments, R5Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R5Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R5Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI2). In some embodiments, R5Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R3Amay be -COOH. In some embodiments, R3Amay be substituted alkyl. In some embodiments, R3Amay be unsubstituted alkyl. In some embodiments, R5Amay be substituted heteroalkyl. In some embodiments, R3Amay be unsubstituted heteroalkyl. In some embodiments, R3Amay be substituted cycloalkyl. In some embodiments, R5Amay be unsubstituted cycloalkyl. In some embodiments, R3Amay be substituted heterocycloalkyl. In some embodiments, R3Amay be unsubstituted heterocycloalkyl. In some embodiments, R5Amay be substituted aryl. In some embodiments, R5Amay be unsubstituted aryl. In some embodiments, R5Amay be substituted heteroaryl. In some embodiments, R3Amay be unsubstituted heteroaryl. In some embodiments, R5Bmay be hydrogen. In some embodiments, R5Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Bmay be -CX3, (e.g., -CF₃, -CCl3, -CBr₃, -CI₃). In some embodiments, R5Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI₂). In some embodiments, R3Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R5Dmay be -COOH. In some embodiments, R5Dmay be substituted alkyl. In some embodiments, R3Bmay be unsubstituted alkyl. In some embodiments, R3Bmay be substituted heteroalkyl. In some embodiments, R5Bmay be unsubstituted heteroalkyl. In some embodiments, R5Bmay be substituted cycloalkyl. In some embodiments, R5Bmay be unsubstituted cycloalkyl. In some embodiments. R5Bmay be substituted heterocycloalkyl. In some embodiments, R3Bmay be unsubstituted heterocycloalkyl. In some embodiments, R3Bmay be substituted aryl. In some embodiments, R5Bmay be unsubstituted aryl. In some embodiments, R5Bmay be substituted heteroaryl. In some embodiments, R5Bmay be unsubstituted heteroaryl.

[0222] In some embodiments R5may be -C(O)R5C. In some embodiments, R5Cmay be hydrogen. In some embodiments, R5Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R5Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R5Cmay be -CHX2, (e g., -CHF2, -CHCk, -CHBr₂, -CHI₂). In some embodiments, R5Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R3Cmay be -COOH. In some embodiments, R5Cmay be substituted alkyl. In some embodiments, R5Cmay be unsubstituted alkyl. In some embodiments, R5Cmay be substituted heteroalkyl. In some embodiments, R5Cmay be unsubstituted heteroalkyl. In some embodiments, R5Cmay be substituted cycloalkyl. In some embodiments, R5Cmay be unsubstituted cycloalkyl. In some embodiments, R5Cmay be substituted heterocycloalkyl. In some embodiments, R5Cmay be unsubstituted heterocycloalkyl. In some embodiments, R5Cmay be substituted aiy I. In some embodiments, R5Cmay be unsubstituted aryl. In some embodiments, R5Cmay be substituted heteroaryl. In some embodiments, R5Cmay be unsubstituted heteroaryl.

[0223] In some embodiments R5may be -C(O)-OR5C. In some embodiments, R5Cmay be hydrogen. In some embodiments, R5Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R5Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R5Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R3Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R5Cmay be -COOH. In some embodiments, R5Cmay be substituted alkyl. In some embodiments, R3Cmay be unsubstituted alkyl. In some embodiments, R3Cmay be substituted heteroalkyl. In some embodiments, R5Cmay be unsubstituted heteroalkyl. In some embodiments, R5Cmay be substituted cycloalkyl. In some embodiments, R5Cmay be unsubstituted cycloalkyl. In some embodiments, R5Cmay be substituted heterocycloalkyl. In some embodiments, R3Cmay be unsubstituted heterocycloalkyl. In some embodiments, R5Cmay be substituted aryl. In some embodiments, R5Cmay be unsubstituted aryl. In some embodiments, R5Cmay be substituted heteroaryl. In some embodiments, R3Cmay be unsubstituted heteroaryl.

[0224] In some embodiments R3may be -C(O)NR3AR3B. In some embodiments, R3Amay be hydrogen. In some embodiments, R3Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R5Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R5Amay be -CHX2. (e.g.. -CHF2. -CHCh, -CHBr2, -CHI₂). In some embodiments, R3Amay be -CH2X, (e.g., -CH2F, -CH₂Cl, -QhBr, -CH2I). In some embodiments, R3Amay be -COOH. In some embodiments, R5Amay be substituted alkyl. In some embodiments, R5Amay be unsubstituted alkyl. In some embodiments, R5Amay be substituted heteroalkyl. In some embodiments, R3Amay be unsubstituted heteroalkyl. In some embodiments, R3Amay besubstituted cycloalkyl. In some embodiments, R5Amay be unsubstituted cycloalkyl. In some embodiments, R3Amay be substituted heterocycloalkyl. In some embodiments, R5Amay be unsubstituted heterocycloalkyl. In some embodiments, R5Amay be substituted aryl. In some embodiments, R3Amay be unsubstituted aryl. In some embodiments, R5Amay be substituted heteroaryl. In some embodiments, R5Amay be unsubstituted heteroaryl. In some embodiments, R3Bmay be hydrogen. In some embodiments, R3Bmay be halogen, (e.g., -F, -Br, -Cl. -I). In some embodiments. R5Bmay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R5Bmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R5Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R5Bmay be -COOH. In some embodiments, R5Bmay be substituted alkyl. In some embodiments, R5Bmay be unsubstituted alkyl. In some embodiments. R5Bmay be substituted heteroalkyl. In some embodiments, R5Bmay be unsubstituted heteroalkyl. In some embodiments, R5Bmay be substituted cycloalkyl. In some embodiments, R3Bmay be unsubstituted cycloalkyl. In some embodiments, R5Bmay be substituted heterocycloalkyl. In some embodiments, R5Bmay be unsubstituted heterocycloalkyl. In some embodiments. R5Bmay be substituted aryl. In some embodiments, R5Dmay be unsubstituted aryl. In some embodiments, R5Bmay be substituted heteroaryl. In some embodiments, R5Bmay be unsubstituted heteroaryl.

[0225] In some embodiments R5may be -OR5D. In some embodiments, R5Dmay be hydrogen. In some embodiments, R5Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R5Dmay be -CX3. (e.g.. -CF3. -CCl3, -CBr₃, -CI₃). In some embodiments, R5Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI2). In some embodiments, R5Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R3Dmay be -COOH. In some embodiments, R5Dmay be substituted alkyl. In some embodiments, R5Dmay be unsubstituted alkyl. In some embodiments, R5Dmay be substituted heteroalkyl. In some embodiments, R3Dmay be unsubstituted heteroalkyl. In some embodiments, R3Dmay be substituted cycloalkyl. In some embodiments, R5Dmay be unsubstituted cycloalkyl. In some embodiments, R5Dmay be substituted heterocycloalkyl. In some embodiments, R3Dmay be unsubstituted heterocycloalkyl. In some embodiments, R3Dmay be substituted aryl. In some embodiments, R3Dmay be unsubstituted aryl. In some embodiments, R3Dmay be substituted heteroaryl. In some embodiments, R3Dmay be unsubstituted heteroaryl.

[0226] In some embodiments R3may be -NR3ASO2R3D. In some embodiments, R3Amay be hydrogen. In some embodiments, R3Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R3Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R5Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R5Amay be -COOH. In some embodiments, R5Amay be substituted alkyl. In some embodiments, R5Amay be unsubstituted alkyl. In some embodiments, R5Amay be substituted heteroalkyl. In some embodiments, R5Amay be unsubstituted heteroalkyl. In some embodiments, R5Amay be substituted cycloalkyl. In some embodiments, R5Amay be unsubstituted cycloalkyl. In some embodiments, R5Amay be substituted heterocycloalkyl. In some embodiments, R5Amay be unsubstituted heterocycloalkyl. In some embodiments, R5Amay be substituted aryl. In some embodiments, R5Amay be unsubstituted aryl. In some embodiments, R5Amay be substituted heteroaryl. In some embodiments, R5Amay be unsubstituted heteroaryl. In some embodiments, R5Dmay be hydrogen. In some embodiments, R5Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R5Dmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R5Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R5Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R5Dmay be -COOH. In some embodiments, R5Dmay be substituted alkyl. In some embodiments, R5Dmay be unsubstituted alkyl. In some embodiments, R5Dmay be substituted heteroalkyl. In some embodiments, R3Dmay be unsubstituted heteroalkyl. In some embodiments, R5Dmay be substituted cycloalkyl. In some embodiments, R5Dmay be unsubstituted cycloalkyl. In some embodiments, R5Dmay be substituted heterocycloalkyl. In some embodiments, R5Dmay be unsubstituted heterocycloalkyl. In some embodiments, R5Dmay be substituted aryl. In some embodiments, R5Dmay be unsubstituted aryl. In some embodiments, R5Dmay be substituted heteroaryl. In some embodiments, R5Dmay be unsubstituted heteroaryl.

[0227] In some embodiments R5may be -NR5AC(O)R5C. In some embodiments, R5Amay be hydrogen. In some embodiments, R5Amay be halogen, (e.g., -F, -Br. -Cl, -I). In some embodiments, R3Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R5Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R5Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R5Amay be -COOH. In some embodiments, R5Amay be substituted alkyl. In some embodiments, R5Amay be unsubstituted alkyl. In some embodiments, R5Amay be substituted heteroalkyl. In some embodiments, R5Amay be unsubstituted heteroalkyl. In some embodiments, R5Amay be substituted cycloalkyl. In some embodiments, R5Amay be unsubstituted cycloalkyl. In some embodiments, R5Amay be substituted heterocycloalkyl. In some embodiments, R5Amay be unsubstituted heterocycloalkyl. In some embodiments, R5Amay be substituted aryl. In someembodiments, R5Amay be unsubstituted aryl. In some embodiments, R5Amay be substituted heteroaryl. In some embodiments, R5Amay be unsubstituted heteroaryl. In some embodiments, R5Cmay be hydrogen. In some embodiments, R5Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R3Cmay be -CX₃, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R5Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R5Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R5Cmay be -COOH. In some embodiments, R5Cmay be substituted alkyl. In some embodiments, R5Cmay be unsubstituted alkyl. In some embodiments, R5Cmay be substituted heteroalkyl. In some embodiments, R5Cmay be unsubstituted heteroalkyl. In some embodiments, R5Cmay be substituted cycloalkyl. In some embodiments, R5Cmay be unsubstituted cycloalkyl. In some embodiments, R5Cmay be substituted heterocycloalkyl. In some embodiments, R5Cmay be unsubstituted heterocycloalkyl. In some embodiments, R5Cmay be substituted aryl. In some embodiments, R5Cmay be unsubstituted aryl. In some embodiments, R5Cmay be substituted heteroaryl. In some embodiments, R5Cmay be unsubstituted heteroaryl.

[0228] In some embodiments R5may be -NR5AC(O)OR5C. In some embodiments, R5Amay be hydrogen. In some embodiments, R5Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R5Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R5Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R5Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R5Amay be -COOH. In some embodiments, R5Amay be substituted alkyl. In some embodiments. R5Amay be unsubstituted alkyl. In some embodiments, R3Amay be substituted heteroalkyl. In some embodiments, R5Amay be unsubstituted heteroalkyl. In some embodiments, R5Amay be substituted cycloalkyl. In some embodiments, R5Amay be unsubstituted cycloalkyl. In some embodiments, R5Amay be substituted heterocycloalkyl. In some embodiments, R5Amay be unsubstituted heterocycloalkyl. In some embodiments, R3Amay be substituted aryl. In some embodiments, R5Amay be unsubstituted aryl. In some embodiments, R5Amay be substituted heteroaryl. In some embodiments, R5Amay be unsubstituted heteroaryl. In some embodiments, R5Cmay be hydrogen. In some embodiments, R5Cmay be halogen, (e.g.. -F, -Br, -Cl. -I). In some embodiments. R5Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R5Cmay' be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI2). In some embodiments, R5Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R5Cmay be -COOH. In some embodiments, R5Cmay be substituted alkyl. In some embodiments, R5Cmay be unsubstituted alkyl. In some embodiments. R5Cmay besubstituted heteroalkyl. In some embodiments, R5Cmay be unsubstituted heteroalkyl. In some embodiments, R5Cmay be substituted cycloalkyl. In some embodiments, R5Cmay be unsubstituted cycloalkyl. In some embodiments. R5Cmay be substituted heterocycloalkyl. In some embodiments, R5Cmay be unsubstituted heterocycloalkyl. In some embodiments, R3Cmay be substituted aryl. In some embodiments, R5Cmay be unsubstituted aryl. In some embodiments, R5Cmay be substituted heteroaryl. In some embodiments, R5Cmay be unsubstituted heteroaryl.

[0229] In some embodiments R5may be -NR5AOR5C. In some embodiments, R’Amay be hydrogen. In some embodiments, R5Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R5Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R5Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R5Amay be -CH2X, (e g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments, R5Amay be -COOH. In some embodiments, R5Amay be substituted alkyl. In some embodiments, R5Amay be unsubstituted alkyl. In some embodiments, R5Amay be substituted heteroalkyl. In some embodiments, R5Amay be unsubstituted heteroalkyl. In some embodiments, R5Amay be substituted cycloalkyl. In some embodiments, R5Amay be unsubstituted cycloalkyl. In some embodiments, R5Amay be substituted heterocycloalkyl. In some embodiments, R5Amay be unsubstituted heterocycloalkyl. In some embodiments, R5Amay be substituted aryl. In some embodiments, R5Amay be unsubstituted aryl. In some embodiments, R5Amay be substituted heteroaryl. In some embodiments, R5Amay be unsubstituted heteroaryl. In some embodiments, R5Cmay be hydrogen. In some embodiments, R5Cmay be halogen, (e.g.. -F. -Br, -Cl, -I). In some embodiments, R3Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R5Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R5Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R5Cmay be -COOH. In some embodiments, R5Cmay be substituted alkyl. In some embodiments, R5Cmay be unsubstituted alkyl. In some embodiments, R5Cmay be substituted heteroalkyl. In some embodiments, R5Cmay be unsubstituted heteroalkyl. In some embodiments, R5Cmay be substituted cycloalkyl. In some embodiments, R5Cmay be unsubstituted cycloalkyl. In some embodiments, R5Cmay be substituted heterocycloalkyl. In some embodiments, R5Cmay be unsubstituted heterocycloalkyl. In some embodiments, R5Cmay be substituted aryl. In some embodiments, R5Cmay be unsubstituted aryl. In some embodiments, R5Cmay be substituted heteroaryl. In some embodiments, R5Cmay be unsubstituted heteroaryl.

[0230] In some embodiments, R5may be substituted alkyl. In some embodiments, R5may be unsubstituted alkyl. In some embodiments, R5may be substituted heteroalkyl. In some embodiments, R5may be unsubstituted heteroalkyl. In some embodiments, R5may be substituted cycloalkyl. In some embodiments, R5may be unsubstituted cycloalkyl. In some embodiments, R5may be substituted heterocycloalkyl. In some embodiments, R5may be unsubstituted heterocycloalkyl. In some embodiments, R5may be substituted aryl. In some embodiments, R5may be unsubstituted aryl. In some embodiments, R5may be substituted heteroaryl. In some embodiments, R5may be unsubstituted heteroaryl.

[0231] In some embodiments, R6may be hydrogen. In some embodiments, R6may' be halogen. In some embodiments, R6may be -CX63, (e.g., CFs. CCh, CBn, Ch). In some embodiments, R6may be -CHX62, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R6may be -CH2X6, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R6may be -OCX63, (e.g., -OCF3, -OCCh, -OCBr3, -OCI3). In some embodiments, R6may be -OCHX62, (e.g., -OCHF2, -OCHCh, -OCHBr2, -OCHI2). In some embodiments, R6may be -OCH2X6, (e.g., -OCH2F, -OCH2CI, -OCH₂Br, -OCH2I). In some embodiments, R6may be -OCH3.

[0232] In some embodiments R6may be -OCH2R6A. In some embodiments, R6Amay be hydrogen. In some embodiments, R6Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R6Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R6Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R6Amay be -COOH. In some embodiments, R6Amay be substituted alkyl. In some embodiments, R6Amay be unsubstituted alkyl. In some embodiments, R6Amay' be substituted heteroalkyl. In some embodiments, R6Amay be unsubstituted heteroalkyl. In some embodiments, R6Amay be substituted cycloalkyl. In some embodiments, R6Amay be unsubstituted cycloalkyl. In some embodiments, R6Amay be substituted heterocycloalkyl. In some embodiments, R6Amay be unsubstituted heterocycloalkyl. In some embodiments, R6Amay be substituted aryl. In some embodiments, R6Amay be unsubstituted aryl. In some embodiments, R6Amay be substituted heteroaryl. In some embodiments, R6Amay be unsubstituted heteroaryl.

[0233] In some embodiments R6may be -N3, -CN.

[0234] In some embodiments R6may be -SOn6R6Dwhereinn6 may be an integer from 0 - 4 (e.g., -S-, -SO-, -SO2-, -SO3-, -SO4-). In some embodiments, R6Dmay be hydrogen. In some embodiments, R6Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Dmay be-CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R6Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R6Dmay be -CH2X, (e.g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments, R6Dmay be -COOH. In some embodiments, R6Dmay be substituted alkyl. In some embodiments, R6Dmay be unsubstituted alkyl. In some embodiments, R6Dmay be substituted heteroalkyl. In some embodiments, R6Dmay be unsubstituted heteroalkyl. In some embodiments, R6Dmay be substituted cycloalkyl. In some embodiments, R6Dmay be unsubstituted cycloalkyl. In some embodiments. R6Dmay be substituted heterocycloalkyl. In some embodiments, R6Dmay be unsubstituted heterocycloalkyl. In some embodiments, R6Dmay be substituted aryl. In some embodiments, R6Dmay be unsubstituted aryl. In some embodiments, R6Dmay be substituted heteroaryl. In some embodiments, R6Dmay be unsubstituted heteroaryl.

[0235] In some embodiments R6may be -SOv6NR6AR6BwhereinV6 may be an integer from 1 to 2 (e.g., -SON-, -SO2N-). In some embodiments, R6Amay be hydrogen. In some embodiments, R6Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R6Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R6Amay be -CH2X, (e.g., -CH2F, -CH₂Cl, -CH2Br, -CH2I). In some embodiments, R6Amay be -COOH. In some embodiments, R6Amay be substituted alkyl. In some embodiments, R6Amay be unsubstituted alkyl. In some embodiments, R6Amay be substituted heteroalkyl. In some embodiments, R6Amay be unsubstituted heteroalkyl. In some embodiments, R6Amay be substituted cycloalkyl. In some embodiments, R6Amay be unsubstituted cycloalkyl. In some embodiments. R6Amay be substituted heterocycloalkyl. In some embodiments, R6Amay be unsubstituted heterocycloalkyl. In some embodiments, R6Amay be substituted aryl. In some embodiments, R6Amay be unsubstituted aryl. In some embodiments, R6Amay be substituted heteroaryl. In some embodiments, R6Amay be unsubstituted heteroaryl. In some embodiments, R6Bmay be hydrogen. In some embodiments, R6Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Bmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R6Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R6Bmay be -CH2X, (e g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R6Bmay be -COOH. In some embodiments, R6Bmay be substituted alkyl. In some embodiments, R6Bmay be unsubstituted alkyl. In some embodiments, R6Bmay be substituted heteroalkyl. In some embodiments, R6Bmay be unsubstituted heteroalkyl. In some embodiments, R6Bmay be substituted cycloalkyl. In some embodiments, R6Bmay be unsubstituted cycloalkyl. In some embodiments, R6Bmay be substituted heterocycloalkyl. In some embodiments, R6Bmay beunsubstituted heterocycloalkyl. In some embodiments, R6Bmay be substituted aryl. In some embodiments, R6Bmay be unsubstituted aryl. In some embodiments, R6Bmay be substituted heteroaryl. In some embodiments, R6Bmay be unsubstituted heteroaryl.

[0236] In some embodiments R6may be -NHC(O)NR6AR6B. In some embodiments, R6Amay be hydrogen. In some embodiments, R6Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R6Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI2). In some embodiments, R6Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R6Amay be -COOH. In some embodiments, R6Amay be substituted alkyl. In some embodiments, R6Amay be unsubstituted alkyl. In some embodiments, R6Amay be substituted heteroalkyl. In some embodiments, R6Amay be unsubstituted heteroalkyl. In some embodiments, R6Amay be substituted cycloalkyl. In some embodiments, R6Amay be unsubstituted cycloalkyl. In some embodiments, R6Amay be substituted heterocycloalkyl. In some embodiments, R6Amay be unsubstituted heterocycloalkyl. In some embodiments, R6Amay be substituted aryl. In some embodiments, R6Amay be unsubstituted aryl. In some embodiments, R6Amay be substituted heteroaryl. In some embodiments, R6Amay be unsubstituted heteroaryl. In some embodiments, R6Bmay be hydrogen. In some embodiments, R6Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Bmay be -CX3, (e.g., -CF₃, -CCl3, -CBr₃, -CI₃). In some embodiments, R6Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R6Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R6Dmay be -COOH. In some embodiments, R6Bmay be substituted alkyl. In some embodiments, R6Bmay be unsubstituted alkyl. In some embodiments, R6Bmay be substituted heteroalkyl. In some embodiments, R6Bmay be unsubstituted heteroalkyl. In some embodiments, R6Bmay be substituted cycloalkyl. In some embodiments, R6Bmay be unsubstituted cycloalkyl. In some embodiments. R6Bmay be substituted heterocycloalkyl. In some embodiments, R6Bmay be unsubstituted heterocycloalkyl. In some embodiments, R6Bmay be substituted aryl. In some embodiments, R6Bmay be unsubstituted aryl. In some embodiments, R6Bmay be substituted heteroaryl. In some embodiments, R6Bmay be unsubstituted heteroaryl

[0237] In some embodiments R6may be -N(0)m6 whereinm6 may be an integer from 1 to 2 (e.g., -N(O), -NO2).

[0238] In some embodiments R6may be -NR6AR6B. In some embodiments, R6Amay be hydrogen. In some embodiments, R6Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R6Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R6Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R6Amay be -COOH. In some embodiments, R6Amay be substituted alkyl. In some embodiments, R6Amay be unsubstituted alkyl. In some embodiments, R6Amay be substituted heteroalkyl. In some embodiments, R6Amay be unsubstituted heteroalkyl. In some embodiments, R6Amay be substituted cycloalkyl. In some embodiments, R6Amay be unsubstituted cycloalkyl. In some embodiments, R6Amay be substituted heterocycloalkyl. In some embodiments, R6Amay be unsubstituted heterocycloalkyl. In some embodiments, R6Amay be substituted aryl. In some embodiments, R6Amay be unsubstituted aryl. In some embodiments, R6Amay be substituted heteroaryl. In some embodiments, R6Amay be unsubstituted heteroaryl. In some embodiments, R6Bmay be hydrogen. In some embodiments, R6Bmay be halogen, (e.g.. -F, -Br, -Cl, -I). In some embodiments, R6Bmay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R6Bmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R6Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R6Bmay be -COOH. In some embodiments, R6Bmay be substituted alkyl. In some embodiments, R6Bmay be unsubstituted alkyl. In some embodiments. R6Bmay be substituted heteroalkyl. In some embodiments, R6Bmay be unsubstituted heteroalkyl. In some embodiments, R6Bmay be substituted cycloalkyl. In some embodiments, R6Bmay be unsubstituted cycloalkyl. In some embodiments, R6Bmay be substituted heterocycloalkyl. In some embodiments, R6Bmay be unsubstituted heterocycloalkyl. In some embodiments. R6Bmay be substituted aryl. In some embodiments, R6Bmay be unsubstituted aryl. In some embodiments, R6Bmay be substituted heteroaryl. In some embodiments, R6Bmay be unsubstituted heteroaryl.

[0239] In some embodiments R6may be -C(O)R6C. In some embodiments, R6Cmay be hydrogen. In some embodiments, R6Cmay be halogen, (e.g., -F. -Br, -Cl, -I). In some embodiments, R6Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R6Cmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI₂). In some embodiments, R6Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R6Cmay be -COOH. In some embodiments, R6Cmay be substituted alkyl. In some embodiments, R6Cmay be unsubstituted alkyl. In some embodiments, R6Cmay be substituted heteroalkyl. In some embodiments, R6Cmay be unsubstituted heteroalkyl. In some embodiments, R6Cmay be substituted cycloalkyl. In some embodiments, R6Cmay be unsubstituted cycloalkyl. In some embodiments, R6Cmay be substituted heterocycloalkyl. In some embodiments, R6Cmay be unsubstituted heterocycloalkyl. In some embodiments, R6Cmay be substituted aryl. In someembodiments, R6Cmay be unsubstituted aryl. In some embodiments, R6Cmay be substituted heteroaryl. In some embodiments, R6Cmay be unsubstituted heteroaryl.

[0240] In some embodiments R6may be -C(O)-OR6C. In some embodiments. R6Cmay be hydrogen. In some embodiments, R6Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R6Cmay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI2). In some embodiments, R6Cmay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R6Cmay be -COOH. In some embodiments, R6Cmay be substituted alkyl. In some embodiments, R6Cmay be unsubstituted alkyl. In some embodiments, R6Cmay be substituted heteroalkyl. In some embodiments, R6Cmay be unsubstituted heteroalkyl. In some embodiments, R6Cmay be substituted cycloalkyl. In some embodiments, R6Cmay be unsubstituted cycloalkyl. In some embodiments, R6Cmay be substituted heterocycloalkyl. In some embodiments, R6Cmay be unsubstituted heterocycloalkyl. In some embodiments, R6Cmay be substituted aryl. In some embodiments, R6Cmay be unsubstituted aryl. In some embodiments, R6Cmay be substituted heteroaryl. In some embodiments, R6Cmay be unsubstituted heteroaryl.

[0241] In some embodiments R6may be -C(O)NR6AR6B. In some embodiments, R6Amay be hydrogen. In some embodiments, R6Amay be halogen, (e.g., -F, -Br. -Cl, -I). In some embodiments, R6Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R6Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R6Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R6Amay be -COOH. In some embodiments, R6Amay be substituted alkyl. In some embodiments, R6Amay be unsubstituted alkyl. In some embodiments, R6Amay be substituted heteroalkyl. In some embodiments, R6Amay be unsubstituted heteroalkyl. In some embodiments, R6Amay be substituted cycloalkyl. In some embodiments, R6Amay be unsubstituted cycloalkyl. In some embodiments, R6Amay be substituted heterocycloalkyl. In some embodiments, R6Amay be unsubstituted heterocycloalkyl. In some embodiments, R6Amay be substituted aryl. In some embodiments, R6Amay be unsubstituted aryl. In some embodiments, R6Amay be substituted heteroaryl. In some embodiments, R6Amay be unsubstituted heteroaryl. In some embodiments, R6Bmay be hydrogen. In some embodiments, R6Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Bmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R6Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R6Bmay be -CH2X, (e.g., -CH2F, -CH₂Cl, -CH2Br, -CH2I). In some embodiments, R6Bmay be -COOH. In some embodiments, R6Bmay be substituted alkyl. In some embodiments, R6Bmay be unsubstituted alkyl. In some embodiments. R6Bmay besubstituted heteroalkyl. In some embodiments, R6Bmay be unsubstituted heteroalkyl. In some embodiments, R6Bmay be substituted cycloalkyl. In some embodiments, R6Bmay be unsubstituted cycloalkyl. In some embodiments. R6Bmay be substituted heterocycloalkyl. In some embodiments, R6Bmay be unsubstituted heterocycloalkyl. In some embodiments, R6Bmay be substituted aryl. In some embodiments, R6Bmay be unsubstituted aryl. In some embodiments, R6Bmay be substituted heteroaryl. In some embodiments, R6Bmay be unsubstituted heteroaryl.

[0242] In some embodiments R6may be -OR6D. In some embodiments, R6Dmay be hydrogen. In some embodiments, R6Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Dmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R6Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R6Dmay be -CH2X, (e g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments, R6Dmay be -COOH. In some embodiments, R6Dmay be substituted alkyl. In some embodiments, R6Dmay be unsubstituted alkyl. In some embodiments, R6Dmay be substituted heteroalkyl. In some embodiments, R6Dmay be unsubstituted heteroalkyl. In some embodiments, R6Dmay be substituted cycloalkyl. In some embodiments, R6Dmay be unsubstituted cycloalkyl. In some embodiments, R6Dmay be substituted heterocycloalkyl. In some embodiments, R6Dmay be unsubstituted heterocycloalkyl. In some embodiments, R6Dmay be substituted aryl. In some embodiments, R6Dmay be unsubstituted aryl. In some embodiments, R6Dmay be substituted heteroaryl. In some embodiments, R6Dmay be unsubstituted heteroaryl.

[0243] In some embodiments R6may be -NR6ASO2R6D. In some embodiments, R6Amay be hydrogen. In some embodiments, R6Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Amay be -CX₃, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R6Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R6Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R6Amay be -COOH. In some embodiments, R6Amay be substituted alkyl. In some embodiments. R6Amay be unsubstituted alkyl. In some embodiments, R6Amay be substituted heteroalkyl. In some embodiments, R6Amay be unsubstituted heteroalkyl. In some embodiments, R6Amay be substituted cycloalkyl. In some embodiments, R6Amay be unsubstituted cycloalkyl. In some embodiments, R6Amay be substituted heterocycloalkyl. In some embodiments, R6Amay be unsubstituted heterocycloalkyl. In some embodiments, R6Amay be substituted aryl. In some embodiments, R6Amay be unsubstituted aryl. In some embodiments, R6Amay be substituted heteroaryl. In some embodiments, R6Amay be unsubstituted heteroaryl. In some embodiments, R6Dmay be hydrogen. In some embodiments, R6Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Dmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R6Dmay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI2). In some embodiments, R6Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R6Dmay be -COOH. In some embodiments, R6Dmay be substituted alkyl. In some embodiments, R6Dmay be unsubstituted alkyl. In some embodiments, R6Dmay be substituted heteroalkyl. In some embodiments. R6Dmay be unsubstituted heteroalkyl. In some embodiments, R6Dmay be substituted cycloalkyl. In some embodiments, R6Dmay be unsubstituted cycloalkyl. In some embodiments, R6Dmay be substituted heterocycloalkyl. In some embodiments, R6Dmay be unsubstituted heterocycloalkyl. In some embodiments, R6Dmay be substituted aryl. In some embodiments, R6Dmay be unsubstituted aryl. In some embodiments, R6Dmay be substituted heteroaryl. In some embodiments, R6Dmay be unsubstituted heteroaryl.

[0244] In some embodiments R6may be -NR6AC(O)R6C. In some embodiments, R6Amay be hydrogen. In some embodiments, R6Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R6Amay be -CHX2. (e.g., -CHF2, -CHCl₂, -CHBr2, -CHI2). In some embodiments, R6Amay be -CH2X, (e g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments. R6Amay be -COOH. In some embodiments, R6Amay be substituted alkyl. In some embodiments, R6Amay be unsubstituted alkyl. In some embodiments, R6Amay be substituted heteroalkyl. In some embodiments, R6Amay be unsubstituted heteroalkyl. In some embodiments, R6Amay be substituted cycloalkyl. In some embodiments, R6Amay be unsubstituted cycloalkyl. In some embodiments, R6Amay be substituted heterocycloalkyl. In some embodiments, R6Amay be unsubstituted heterocycloalkyl. In some embodiments, R6Amay be substituted aryl. In some embodiments, R6Amay be unsubstituted aryl. In some embodiments, R6Amay be substituted heteroaryl. In some embodiments, R6Amay be unsubstituted heteroaryl. In some embodiments, R6Cmay be hydrogen. In some embodiments, R6Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Cmay be -CX3, (e.g., -CF₃, -CCl3, -CBr₃, -CI₃). In some embodiments, R6Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R6Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R6Cmay be -COOH. In some embodiments, R6Cmay be substituted alkyl. In some embodiments, R6Cmay be unsubstituted alkyl. In some embodiments, R6Cmay be substituted heteroalkyl. In some embodiments, R6Cmay be unsubstituted heteroalkyl. In some embodiments, R6Cmay be substituted cycloalkyl. In some embodiments, R6Cmay be unsubstituted cycloalkyl. In some embodiments. R6Cmay be substituted heterocycloalkyl. Insome embodiments, R6Cmay be unsubstituted heterocycloalkyl. In some embodiments, R6Cmay be substituted aryl. In some embodiments, R6Cmay be unsubstituted aryl. In some embodiments, R6Cmay be substituted heteroaryl. In some embodiments, R6Cmay be unsubstituted heteroaryl.

[0245] In some embodiments R6may be -NR6AC(O)OR6C. In some embodiments, R6Amay be hydrogen. In some embodiments, R6Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Amay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R6Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R6Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R6Amay be -COOH. In some embodiments, R6Amay be substituted alkyl. In some embodiments, R6Amay be unsubstituted alkyl. In some embodiments, R6Amay be substituted heteroalkyl. In some embodiments, R6Amay be unsubstituted heteroalkyl. In some embodiments, R6Amay be substituted cycloalkyl. In some embodiments, R6Amay be unsubstituted cycloalkyl. In some embodiments, R6Amay be substituted heterocycloalkyl. In some embodiments, R6Amay be unsubstituted heterocycloalkyl. In some embodiments, R6Amay be substituted aryl. In some embodiments, R6Amay be unsubstituted aryl. In some embodiments, R6Amay be substituted heteroaryl. In some embodiments, R6Amay be unsubstituted heteroaryl. In some embodiments, R6Cmay be hydrogen. In some embodiments, R6Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Cmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R6Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R6Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br. -CH2I). In some embodiments, R6Cmay be -COOH. In some embodiments, R6Cmay be substituted alkyl. In some embodiments, R6Cmay be unsubstituted alkyl. In some embodiments, R6Cmay be substituted heteroalkyl. In some embodiments, R6Cmay be unsubstituted heteroalkyl. In some embodiments, R6Cmay be substituted cycloalkyl. In some embodiments, R6Cmay be unsubstituted cycloalkyl. In some embodiments, R6Cmay be substituted heterocycloalkyl. In some embodiments, R6Cmay be unsubstituted heterocycloalkyl. In some embodiments, R6Cmay be substituted aryl. In some embodiments, R6Cmay be unsubstituted aryl. In some embodiments, R6Cmay be substituted heteroaryl. In some embodiments, R6Cmay be unsubstituted heteroaryl.

[0246] In some embodiments R6may be -NR6AOR6C. In some embodiments, R6Amay be hydrogen. In some embodiments, R6Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R6Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI₂). In some embodiments, R6Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R6Amay be -COOH. In some embodiments, R6Amay be substituted alkyl. In some embodiments, R6Amay be unsubstituted alkyl. In some embodiments, R6Amay be substituted heteroalkyl. In some embodiments, R6Amay be unsubstituted heteroalkyl. In some embodiments, R6Amay be substituted cycloalkyl. In some embodiments, R6Amay be unsubstituted cycloalkyl. In some embodiments, R6Amay be substituted heterocycloalkyl. In some embodiments, R6Amay be unsubstituted heterocycloalkyl. In some embodiments, R6Amay be substituted aryl. In some embodiments, R6Amay be unsubstituted aryl. In some embodiments, R6Amay be substituted heteroaryl. In some embodiments, R6Amay be unsubstituted heteroaryl. In some embodiments, R6Cmay be hydrogen. In some embodiments, R6Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R6Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R6Cmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr2, -CHI2). In some embodiments, R6Cmay be -CH2X, (e.g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments, R6Cmay be -COOH. In some embodiments, R6Cmay be substituted alkyl. In some embodiments, R6Cmay be unsubstituted alkyl. In some embodiments. R6Cmay be substituted heteroalkyl. In some embodiments. R6Cmay be unsubstituted heteroalkyl. In some embodiments, R6Cmay be substituted cycloalkyl. In some embodiments, R6Cmay be unsubstituted cycloalkyl. In some embodiments, R6Cmay be substituted heterocycloalkyl. In some embodiments, R6Cmay be unsubstituted heterocycloalkyl. In some embodiments, R6Cmay be substituted aryl. In some embodiments, R6Cmay be unsubstituted aryl. In some embodiments, R6Cmay be substituted heteroaryl. In some embodiments, R6Cmay be unsubstituted heteroaryl.

[0247] In some embodiments, R6may be substituted alkyl. In some embodiments, R6may be unsubstituted alkyl. In some embodiments, R6may be substituted heteroalkyl. In some embodiments, R6may be unsubstituted heteroalkyl. In some embodiments, R6may be substituted cycloalkyl. In some embodiments, R6may be unsubstituted cycloalkyl. In some embodiments, R6may be substituted heterocycloalkyl. In some embodiments, R6may be unsubstituted heterocycloalkyl. In some embodiments, R6may be substituted aryl. In some embodiments, R6may be unsubstituted aryl. In some embodiments, R6may be substituted heteroaryl. In some embodiments, R6may be unsubstituted heteroaryl.

[0248] In some embodiments, R7may be hydrogen. In some embodiments, R7may be halogen. In some embodiments, R7may be -CX73, (e.g., CFs, CCI3, CBn, CI3). In some embodiments, R7may be -CHX72, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R7may be -CH2X7, (e.g., -CH2F, -CH2C1, -CH2Br, -CH2I). In someembodiments, R7may be -OCX7₃, (e.g., -OCF3, -OCCh, -OCBr3, -OCI3). In some embodiments, R7may be -OCHX72, (e g., -OCHF2, -OCHCh, -OCHBr2, -OCHI2). In some embodiments, R7may be -OCH2X7, (e g., -OCH2F, -OCH2CI, -OCH₂Br, -OCH2I). In some embodiments, R7may be -OCH3.

[0249] In some embodiments, R7may be -OCH2R7A. In some embodiments, R7Amay be hydrogen. In some embodiments, R7Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R7Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R7Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R7Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R7Amay be -COOH. In some embodiments, R7Amay be substituted alkyl. In some embodiments, R7Amay be unsubstituted alkyl. In some embodiments, R7Amay be substituted heteroalkyl. In some embodiments, R7Amay be unsubstituted heteroalkyl. In some embodiments, R7Amay be substituted cycloalkyl. In some embodiments, R7Amay be unsubstituted cycloalkyl. In some embodiments, R7Amay be substituted heterocycloalkyl. In some embodiments, R7Amay be unsubstituted heterocycloalkyl. In some embodiments, R7Amay be substituted aryl. In some embodiments, R7Amay be unsubstituted aryl. In some embodiments, R7Amay be substituted heteroaryl. In some embodiments, R7Amay be unsubstituted heteroaryl.

[0250] In some embodiments, R7may be -N3, -CN.

[0251] In some embodiments, R7may be -SOn7R7Dwhereinn7may be an integer from 0 - 4 (e.g., -S-, -SO-, -SO2-, -SO3-, -SO4-). In some embodiments, R7Dmay be hydrogen. In some embodiments, R7Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R7Dmay be -CX3. (e.g.. -CF3. -CCl₃, -CBr₃, -CI₃). In some embodiments, R7Dmay be -CHX2. (e.g.. -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R7Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R7Dmay be -COOH. In some embodiments, R7Dmay be substituted alkyl. In some embodiments, R7Dmay be unsubstituted alkyl. In some embodiments, R7Dmay be substituted heteroalkyl. In some embodiments. R7Dmay be unsubstituted heteroalkyl. In some embodiments, R7Dmay be substituted cycloalkyl. In some embodiments, R7Dmay be unsubstituted cycloalkyl. In some embodiments, R7Dmay be substituted heterocycloalkyl. In some embodiments, R7Dmay be unsubstituted heterocycloalkyl. In some embodiments, R7Dmay be substituted aryl. In some embodiments, R7Bmay be unsubstituted aryl. In some embodiments. R7Dmay be substituted heteroaryl. In some embodiments, R7Dmay be unsubstituted heteroaryl.

[0252] In some embodiments, R7may be -SOv7NR7AR7Bwhereinv7may be an integer from 1 to 2 (e.g., -SON-, -SO2N-). In some embodiments, R7Amay be hydrogen. In some embodiments, R7Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R7Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R7Amay be -CHX₂, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R7Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R7Amay be -COOH. In some embodiments, R7Amay be substituted alkyl. In some embodiments, R7Amay be unsubstituted alkyl. In some embodiments, R7Amay be substituted heteroalkyl. In some embodiments, R7Amay be unsubstituted heteroalkyl. In some embodiments, R7Amay be substituted cycloalkyl. In some embodiments, R7Amay be unsubstituted cycloalkyl. In some embodiments, R7Amay be substituted heterocycloalkyl. In some embodiments, R7Amay be unsubstituted heterocycloalkyl. In some embodiments, R7Amay be substituted aryl. In some embodiments, R7Amay be unsubstituted aryl. In some embodiments, R7Amay be substituted heteroaryl. In some embodiments, R7Amay be unsubstituted heteroaryl. In some embodiments, R7Bmay be hydrogen. In some embodiments, R7Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R7Dmay be -CX3. (e.g., -CF3. -CCl₃, -CBr₃, -CI₃). In some embodiments, R7Dmay be -CHX2, (e g., -CHF2, -CHCh, -CHBr2, -CHI₂). In some embodiments, R7Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R7Bmay be -COOH. In some embodiments, R7Bmay be substituted alkyl. In some embodiments, R7Bmay be unsubstituted alkyl. In some embodiments, R7Bmay be substituted heteroalkyl. In some embodiments, R7Bmay be unsubstituted heteroalkyl. In some embodiments, R7Bmay be substituted cycloalkyl. In some embodiments, R7Bmay be unsubstituted cycloalkyl. In some embodiments, R7Bmay be substituted heterocycloalkyl. In some embodiments, R7Bmay be unsubstituted heterocycloalkyl. In some embodiments, R7Bmay be substituted aryl. In some embodiments, R7Bmay be unsubstituted aryl. In some embodiments, R7Bmay be substituted heteroaryl. In some embodiments, R7Bmay be unsubstituted heteroaryl.

[0253] In some embodiments, R7may be -NHC(O)NR7AR7B. In some embodiments, R7Amay be hydrogen. In some embodiments, R7Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R7Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R7Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R7Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R7Amay be -COOH. In some embodiments, R7Amay be substituted alkyl. In some embodiments, R7Amay be unsubstituted alkyl. In some embodiments, R7Amay be substituted heteroalkyl. In some embodiments, R7Amay be unsubstituted heteroalkyl. In some embodiments, R7Amay besubstituted cycloalkyl. In some embodiments, R7Amay be unsubstituted cycloalkyl. In some embodiments, R7Amay be substituted heterocycloalkyl. In some embodiments, R7Amay be unsubstituted heterocycloalkyl. In some embodiments, R7Amay be substituted aryl. In some embodiments, R7Amay be unsubstituted aryl. In some embodiments, R7Amay be substituted heteroaryl. In some embodiments, R7Amay be unsubstituted heteroaryl. In some embodiments, R7Bmay be hydrogen. In some embodiments, R7Bmay be halogen, (e.g., -F, -Br, -Cl. -I). In some embodiments. R7Bmay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R7Bmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R7Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R7Bmay be -COOH. In some embodiments, R7Bmay be substituted alkyl. In some embodiments, R7Bmay be unsubstituted alkyl. In some embodiments. R7Bmay be substituted heteroalkyl. In some embodiments, R7Bmay be unsubstituted heteroalkyl. In some embodiments, R7Bmay be substituted cycloalkyl. In some embodiments, R7Bmay be unsubstituted cycloalkyl. In some embodiments, R7Bmay be substituted heterocycloalkyl. In some embodiments, R7Bmay be unsubstituted heterocycloalkyl. In some embodiments. R7Bmay be substituted aryl. In some embodiments, R7Bmay be unsubstituted aryl. In some embodiments, R7Bmay be substituted heteroaryl. In some embodiments, R7Bmay be unsubstituted heteroaryl.

[0254] In some embodiments, R7may be -N(O)m7whereinm7may be an integer from 1 to 2 (e.g., -N(O), -NO2).

[0255] In some embodiments, R7may be -NR7AR7B. In some embodiments, R7Amay be hydrogen. In some embodiments, R7Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R7Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R7Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R7Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R7Amay be -COOH. In some embodiments, R7Amay be substituted alkyl. In some embodiments. R7Amay be unsubstituted alkyl. In some embodiments, R7Amay be substituted heteroalkyl. In some embodiments, R7Amay be unsubstituted heteroalkyl. In some embodiments, R7Amay be substituted cycloalkyl. In some embodiments, R7Amay be unsubstituted cycloalkyl. In some embodiments, R7Amay be substituted heterocycloalkyl. In some embodiments, R7Amay be unsubstituted heterocycloalkyl. In some embodiments, R7Amay be substituted aryl. In some embodiments, R7Amay be unsubstituted aryl. In some embodiments, R7Amay be substituted heteroaryl. In some embodiments, R7Amay be unsubstituted heteroaryl. In some embodiments, R7Bmay be hydrogen. In some embodiments, R7Bmay be halogen, (e.g.. -F, -Br, -Cl, -I). In some embodiments, R7Bmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R7Bmay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI2). In some embodiments, R7Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R7Bmay be -COOH. In some embodiments, R7Bmay be substituted alkyl. In some embodiments, R7Bmay be unsubstituted alkyl. In some embodiments, R7Bmay be substituted heteroalkyl. In some embodiments. R7Bmay be unsubstituted heteroalkyl. In some embodiments, R7Bmay be substituted cycloalkyl. In some embodiments, R7Bmay’ be unsubstituted cycloalkyl. In some embodiments, R7Bmay be substituted heterocycloalkyl. In some embodiments, R7Bmay be unsubstituted heterocycloalkyl. In some embodiments, R7Bmay be substituted aryl. In some embodiments, R7Bmay be unsubstituted aryl. In some embodiments, R7Bmay be substituted heteroaryl. In some embodiments, R7Bmay be unsubstituted heteroaryl.

[0256] In some embodiments, R7may be -C(O)R7C. In some embodiments, R7Cmay be hydrogen. In some embodiments, R7Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R7Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R7Cmay be -CHX2. (e.g., -CHF2, -CHCl₂, -CHBr2, -CHI2). In some embodiments, R7Cmay be -CH2X, (e g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments. R7Cmay be -COOH. In some embodiments, R7Cmay be substituted alkyl. In some embodiments, R7Cmay be unsubstituted alkyl. In some embodiments, R7Cmay be substituted heteroalkyl. In some embodiments, R7Cmay be unsubstituted heteroalkyl. In some embodiments, R7Cmay be substituted cycloalkyl. In some embodiments, R7Cmay be unsubstituted cycloalkyl. In some embodiments, R7Cmay be substituted heterocycloalkyl. In some embodiments, R7Cmay be unsubstituted heterocycloalkyl. In some embodiments, R7Cmay be substituted aryl. In some embodiments, R7Cmay be unsubstituted aryl. In some embodiments, R7Cmay be substituted heteroaryl. In some embodiments, R7Cmay be unsubstituted heteroaryl.

[0257] In some embodiments, R7may be -C(O)-OR7C. In some embodiments, R7Cmay be hydrogen. In some embodiments, R7Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R7Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R7Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R7Cmay be -CH2X, (e.g., -CH2F, -CH₂Cl, -CH2Br, -CH2I). In some embodiments, R7Cmay be -COOH. In some embodiments, R7Cmay be substituted alkyl. In some embodiments, R7Cmay be unsubstituted alkyl. In some embodiments, R7Cmay be substituted heteroalkyl. In some embodiments, R7Cmay be unsubstituted heteroalkyl. In some embodiments, R7Cmay be substituted cycloalkyl. In some embodiments, R7Cmay be unsubstituted cycloalkyl. In someembodiments, R7Cmay be substituted heterocycloalkyl. In some embodiments, R7Cmay be unsubstituted heterocycloalkyl. In some embodiments, R7Cmay be substituted aryl. In some embodiments, R7Cmay be unsubstituted aryl. In some embodiments, R7Cmay be substituted heteroaryl. In some embodiments, R7Cmay be unsubstituted heteroaryl.

[0258] In some embodiments, R7may be -C(O)NR7AR7B. In some embodiments, R7Amay be hydrogen. In some embodiments, R7Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R7Amay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R7Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R7Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R7Amay be -COOH. In some embodiments, R7Amay be substituted alkyl. In some embodiments, R7Amay be unsubstituted alkyl. In some embodiments, R7Amay be substituted heteroalkyl. In some embodiments, R7Amay be unsubstituted heteroalkyl. In some embodiments, R7Amay be substituted cycloalkyl. In some embodiments, R7Amay be unsubstituted cycloalkyl. In some embodiments, R7Amay be substituted heterocycloalkyl. In some embodiments, R7Amay be unsubstituted heterocycloalkyl. In some embodiments, R7Amay be substituted aryl. In some embodiments, R7Amay be unsubstituted aryl. In some embodiments, R7Amay be substituted heteroaryl. In some embodiments, R7Amay be unsubstituted heteroaryl. In some embodiments, R7Bmay be hydrogen. In some embodiments, R7Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R7Bmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R7Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R7Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br. -CH2I). In some embodiments, R7Bmay be -COOH. In some embodiments, R7Bmay be substituted alkyl. In some embodiments, R7Bmay be unsubstituted alkyl. In some embodiments, R7Bmay be substituted heteroalky I. In some embodiments, R7Bmay be unsubstituted heteroalkyl. In some embodiments, R7Bmay be substituted cycloalkyl. In some embodiments, R7Bmay be unsubstituted cycloalkyl. In some embodiments, R7Bmay be substituted heterocycloalkyl. In some embodiments, R7Bmay be unsubstituted heterocycloalkyl. In some embodiments, R7Bmay be substituted aryl. In some embodiments, R7Bmay be unsubstituted aryl. In some embodiments, R7Bmay be substituted heteroaryl. In some embodiments, R7Bmay be unsubstituted heteroaryl.

[0259] In some embodiments, R7may be -OR7D. In some embodiments, R7Dmay be hydrogen. In some embodiments, R7Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R7Dmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R7Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI₂). In some embodiments, R7Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R7Dmay be -COOH. In some embodiments, R7Dmay be substituted alkyl. In some embodiments, R7Dmay be unsubstituted alkyl. In some embodiments, R7Dmay be substituted heteroalkyl. In some embodiments, R7Dmay be unsubstituted heteroalkyl. In some embodiments, R7Dmay be substituted cycloalkyl. In some embodiments, R7Dmay be unsubstituted cycloalkyl. In some embodiments, R7Dmay be substituted heterocycloalkyl. In some embodiments, R7Dmay be unsubstituted heterocycloalkyl. In some embodiments, R7Dmay be substituted aryl. In some embodiments, R7Bmay be unsubstituted aryl. In some embodiments, R7Dmay be substituted heteroaryl. In some embodiments, R7Dmay be unsubstituted heteroaryl.

[0260] In some embodiments, R7may be -NR7ASO2R7D. In some embodiments, R7Amay be hydrogen. In some embodiments, R7Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R7Amay be -CX3. (e.g., -CF3. -CCl3, -CBr₃, -CI₃). In some embodiments, R7Amay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R7Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R7Amay be -COOH. In some embodiments, R7Amay be substituted alkyl. In some embodiments, R7Amay be unsubstituted alkyl. In some embodiments, R7Amay be substituted heteroalkyl. In some embodiments, R7Amay be unsubstituted heteroalkyl. In some embodiments, R7Amay be substituted cycloalkyl. In some embodiments, R7Amay be unsubstituted cycloalkyl. In some embodiments, R7Amay be substituted heterocycloalkyl. In some embodiments, R7Amay be unsubstituted heterocycloalkyl. In some embodiments, R7Amay be substituted aryl. In some embodiments, R7Amay be unsubstituted aryl. In some embodiments, R7Amay be substituted heteroaryl. In some embodiments, R7Amay be unsubstituted heteroaryl. In some embodiments, R7Dmay be hydrogen. In some embodiments, R7Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R7Dmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R7Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R7Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R7Dmay be -COOH. In some embodiments, R7Dmay be substituted alkyl. In some embodiments, R7Dmay be unsubstituted alkyl. In some embodiments, R7Dmay be substituted heteroalkyl. In some embodiments. R7Dmay be unsubstituted heteroalkyl. In some embodiments, R7Dmay be substituted cycloalkyl. In some embodiments, R7Dmay be unsubstituted cycloalkyl. In some embodiments, R7Dmay be substituted heterocycloalkyl. In some embodiments, R7Dmay be unsubstituted heterocycloalkyl. In some embodiments, R7Dmay be substituted aryl. In some embodiments, R7Bmay be unsubstituted aryl. In someembodiments, R7Dmay be substituted heteroaryl. In some embodiments, R7Dmay be unsubstituted heteroaryl.

[0261] In some embodiments, R7may be -NR7AC(O)R7C. In some embodiments, R7Amay be hydrogen. In some embodiments, R7Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R7Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R7Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R7Amay be -CH2X, (e g., -CH2F, -CH2CI, -C BBr, -CH2I). In some embodiments, R7Amay be -COOH. In some embodiments, R7Amay be substituted alkyl. In some embodiments, R7Amay be unsubstituted alkyl. In some embodiments, R7Amay be substituted heteroalkyl. In some embodiments, R7Amay be unsubstituted heteroalkyl. In some embodiments, R7Amay be substituted cycloalkyl. In some embodiments, R7Amay be unsubstituted cycloalkyl. In some embodiments, R7Amay be substituted heterocycloalkyl. In some embodiments, R7Amay be unsubstituted heterocycloalkyl. In some embodiments, R7Amay be substituted aryl. In some embodiments, R7Amay be unsubstituted aryl. In some embodiments, R7Amay be substituted heteroaryl. In some embodiments, R7Amay be unsubstituted heteroaryl. In some embodiments, R7Cmay be hydrogen. In some embodiments, R7Cmay be halogen, (e.g.. -F, -Br, -Cl, -I). In some embodiments, R7Cmay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R7Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI2). In some embodiments, R7Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R7Cmay be -COOH. In some embodiments, R7Cmay be substituted alkyl. In some embodiments, R7Cmay be unsubstituted alkyl. In some embodiments. R7Cmay be substituted heteroalkyl. In some embodiments, R7Cmay be unsubstituted heteroalkyl. In some embodiments, R7Cmay be substituted cycloalkyl. In some embodiments, R7Cmay be unsubstituted cycloalkyl. In some embodiments, R7Cmay be substituted heterocycloalkyl. In some embodiments, R7Cmay be unsubstituted heterocycloalkyl. In some embodiments. R7Cmay be substituted aryl. In some embodiments, R7Cmay be unsubstituted aryl. In some embodiments, R7Cmay be substituted heteroaryl. In some embodiments, R7Cmay be unsubstituted heteroaryl.

[0262] In some embodiments, R7may be -NR7AC(O)OR7C. In some embodiments, R7Amay be hydrogen. In some embodiments, R7Amay be halogen, (e.g., -F, -Br. -Cl, -I). In some embodiments, R7Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R7Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R7Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R7Amay be -COOH. In some embodiments, R7Amay be substituted alkyl. In some embodiments, R7Amay beunsubstituted alkyl. In some embodiments, R7Amay be substituted heteroalkyl. In some embodiments, R7Amay be unsubstituted heteroalkyl. In some embodiments, R7Amay be substituted cycloalkyl. In some embodiments, R7Amay be unsubstituted cycloalkyl. In some embodiments, R7Amay be substituted heterocycloalkyl. In some embodiments, R7Amay be unsubstituted heterocycloalkyl. In some embodiments, R7Amay be substituted aryl. In some embodiments, R7Amay be unsubstituted aryl. In some embodiments, R7Amay be substituted heteroaryl. In some embodiments, R7Amay be unsubstituted heteroaryl. In some embodiments, R7Cmay be hydrogen. In some embodiments, R7Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R7Cmay be -CX₃, (e.g., -CF₃, -CCl₃, -CBr₃, -CI3). In some embodiments, R7Cmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R7Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R7Cmay be -COOH. In some embodiments, R7Cmay be substituted alkyl. In some embodiments, R7Cmay be unsubstituted alkyl. In some embodiments, R7Cmay be substituted heteroalkyl. In some embodiments, R7Cmay be unsubstituted heteroalkyl. In some embodiments, R7Cmay be substituted cycloalkyl. In some embodiments, R7Cmay be unsubstituted cycloalkyl. In some embodiments. R7Cmay be substituted heterocycloalkyl. In some embodiments, R7Cmay be unsubstituted heterocycloalkyl. In some embodiments, R7Cmay be substituted aryl. In some embodiments, R7Cmay be unsubstituted aryl. In some embodiments, R7Cmay be substituted heteroaryl. In some embodiments, R7Cmay be unsubstituted heteroaryl.

[0263] In some embodiments, R7may be -NR7AOR7C. In some embodiments. R7Amay be hydrogen. In some embodiments, R7Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R7Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R7Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R7Amay be -CH2X, (e g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments, R7Amay be -COOH. In some embodiments, R7Amay be substituted alkyl. In some embodiments, R7Amay be unsubstituted alkyl. In some embodiments, R7Amay be substituted heteroalkyl. In some embodiments, R7Amay be unsubstituted heteroalkyl. In some embodiments, R7Amay be substituted cycloalkyl. In some embodiments, R7Amay be unsubstituted cycloalkyl. In some embodiments, R7Amay be substituted heterocycloalkyl. In some embodiments, R7Amay be unsubstituted heterocycloalkyl. In some embodiments, R7Amay be substituted aryl. In some embodiments, R7Amay be unsubstituted aryl. In some embodiments, R7Amay be substituted heteroaryl. In some embodiments, R7Amay be unsubstituted heteroaryl. In some embodiments, R7Cmay be hydrogen. In some embodiments, R7Cmay be halogen, (e.g.. -F, -Br, -Cl, -I). In some embodiments, R7Cmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R7Cmay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI2). In some embodiments, R7Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R7Cmay be -COOH. In some embodiments, R7Cmay be substituted alkyl. In some embodiments, R7Cmay be unsubstituted alkyl. In some embodiments, R7Cmay be substituted heteroalkyl. In some embodiments. R7Cmay be unsubstituted heteroalkyl. In some embodiments, R7Cmay be substituted cycloalkyl. In some embodiments, R7Cmay’ be unsubstituted cycloalkyl. In some embodiments, R7Cmay be substituted heterocycloalkyl. In some embodiments, R7Cmay be unsubstituted heterocycloalkyl. In some embodiments, R7Cmay be substituted aryl. In some embodiments, R7Cmay be unsubstituted aryl. In some embodiments, R7Cmay be substituted heteroaryl. In some embodiments, R7Cmay be unsubstituted heteroaryl.

[0264] In some embodiments, R7may be substituted alkyl. In some embodiments, R7may be unsubstituted alkyl. In some embodiments, R7may be substituted heteroalkyl. In some embodiments, R7may be unsubstituted heteroalkyl. In some embodiments, R7may be substituted cycloalkyl. In some embodiments, R7may be unsubstituted cycloalkyl. In some embodiments, R7may be substituted heterocycloalkyl. In some embodiments, R7may be unsubstituted heterocycloalkyl. In some embodiments, R7may be substituted aryl. In some embodiments, R7may be unsubstituted aryl. In some embodiments, R7may be substituted heteroaryl. In some embodiments, R7may be unsubstituted heteroaryl.

[0265] In some embodiments, R8may be hydrogen. In some embodiments, R8may be halogen. In some embodiments, R8may be -CX83, (e.g., CF3, CCI3, CBn, CI3). In some embodiments, R8may be -CHX82, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R8may be -CH2X8, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R8may be -OCX83, (e.g., -OCF3, -OCCI3, -OCBr3, -OCI3). In some embodiments, R8may be -OCHX82, (e.g., -OCHF2, -OCHCh. -OCHBr2, -OCHI2). In some embodiments, R8may be -OCH2X8, (e.g., -OCH2F, -OCH2CI, -OCFBBr, -OCH2I). In some embodiments, R8may be -OCHs.

[0266] In some embodiments, R8may be -OCH2R8A. In some embodiments, R8Amay be hydrogen. In some embodiments, R8Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Amay be -CX3. (e.g.. -CF3. -CCl3, -CBr₃, -CI₃). In some embodiments, R8Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI2). In some embodiments, R8Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R8Amay be -COOH. In some embodiments, R8Amay be substituted alkyl. In some embodiments, R8Amay beunsubstituted alkyl. In some embodiments, R8Amay be substituted heteroalkyl. In some embodiments, R8Amay be unsubstituted heteroalkyl. In some embodiments, R8Amay be substituted cycloalkyl. In some embodiments, R8Amay be unsubstituted cycloalkyl. In some embodiments, R8Amay be substituted heterocycloalkyl. In some embodiments, R8Amay be unsubstituted heterocycloalkyl. In some embodiments, R8Amay be substituted aryl. In some embodiments, R8Amay be unsubstituted aryl. In some embodiments, R8Amay be substituted heteroaryl. In some embodiments, R8Amay be unsubstituted heteroaryl.

[0267] In some embodiments, R8may be -N3, -CN.

[0268] In some embodiments, R8may be -SOnsR8Dwhereinns may be an integer from 0 - 4 (e.g., -S-, -SO-, -SO2-, -SO?-, -SO4-). In some embodiments, R8Dmay be hydrogen. In some embodiments, R8Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Dmay be -CX?, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R8Dmay be -CHX2. (e.g., -CHF2, -CHCh, -CHBr. -CHI2). In some embodiments, R8Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R8Dmay be -COOH. In some embodiments, R8Dmay be substituted alkyl. In some embodiments, R8Dmay be unsubstituted alkyl. In some embodiments, R8Dmay be substituted heteroalkyl. In some embodiments, R8Dmay be unsubstituted heteroalkyl. In some embodiments, R8Dmay be substituted cycloalkyl. In some embodiments, R8Dmay be unsubstituted cycloalkyl. In some embodiments, R8Dmay be substituted heterocycloalky 1. In some embodiments, R8Dmay be unsubstituted heterocycloalkyl. In some embodiments, R8Dmay be substituted aryl. In some embodiments, R8Dmay be unsubstituted aryl. In some embodiments, R8Dmay be substituted heteroaryl. In some embodiments, R8Dmay be unsubstituted heteroaryl.

[0269] In some embodiments, R8may be -SOvsNR8AR8Bwhereinvs may be an integer from 1 to 2 (e.g., -SON-, -SO2N-). In some embodiments, R8Amay be hydrogen. In some embodiments, R8Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Amay be -CX3, (e.g., -CF3. -CCl3, -CBr₃, -CI₃). In some embodiments, R8Amay be -CHX2. (e.g.. -CHF2, -CHCh. -CHBr2, -CHI2). In some embodiments. R8Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R8Amay be -COOH. In some embodiments, R8Amay be substituted alkyl. In some embodiments, R8Amay be unsubstituted alkyl. In some embodiments, R8Amay be substituted heteroalkyl. In some embodiments, R8Amay be unsubstituted heteroalkyl. In some embodiments, R8Amay be substituted cycloalkyl. In some embodiments, R8Amay be unsubstituted cycloalkyl. In some embodiments, R8Amay be substituted heterocycloalkyl. In some embodiments, R8Amay be unsubstituted heterocycloalkyl. In some embodiments, R8Amay be substituted aryl. In some embodiments,R8Amay be unsubstituted aryl. In some embodiments, R8Amay be substituted heteroaryl. In some embodiments, R8Amay be unsubstituted heteroaryl. In some embodiments, R8Bmay be hydrogen. In some embodiments, R8Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Bmay be -CX₃, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R8Bmay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R8Bmay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R8Bmay be -COOH. In some embodiments, R8Bmay be substituted alkyl. In some embodiments, R8Bmay be unsubstituted alkyl. In some embodiments, R8Bmay be substituted heteroalkyl. In some embodiments, R8Bmay be unsubstituted heteroalkyl. In some embodiments, R8Bmay be substituted cycloalkyl. In some embodiments, R8Bmay be unsubstituted cycloalkyl. In some embodiments, R8Bmay be substituted heterocycloalkyl. In some embodiments, R8Bmay be unsubstituted heterocycloalkyl. In some embodiments, R8Bmay be substituted aryl. In some embodiments, R8Bmay be unsubstituted aryl. In some embodiments, R8Bmay be substituted heteroaryl. In some embodiments, R8Bmay be unsubstituted heteroaryl.

[0270] In some embodiments, R8may be -NHC(O)NR8AR8B. In some embodiments, R8Amay be hydrogen. In some embodiments, R8Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R8Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R8Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R8Amay be -COOH. In some embodiments, R8Amay be substituted alkyl. In some embodiments, R8Amay be unsubstituted alkyl. In some embodiments, R8Amay be substituted heteroalkyl. In some embodiments, R8Amay be unsubstituted heteroalkyl. In some embodiments, R8Amay be substituted cycloalkyl. In some embodiments, R8Amay be unsubstituted cycloalkyl. In some embodiments, R8Amay be substituted heterocycloalkyl. In some embodiments, R8Amay be unsubstituted heterocycloalkyl. In some embodiments, R8Amay be substituted aryl. In some embodiments, R8Amay be unsubstituted aryl. In some embodiments, R8Amay be substituted heteroaryl. In some embodiments, R8Amay be unsubstituted heteroaryl. In some embodiments, R8Bmay be hydrogen. In some embodiments, R8Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Bmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI3). In some embodiments, R8Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R8Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R8Bmay be -COOH. In some embodiments, R8Bmay be substituted alkyl. In some embodiments, R8Bmay be unsubstituted alkyl. In some embodiments, R8Bmay be substituted heteroalkyl. In some embodiments. R8Bmay be unsubstituted heteroalkyl. In someembodiments, R8Bmay be substituted cycloalkyl. In some embodiments, R8Bmay be unsubstituted cycloalkyl. In some embodiments, R8Bmay be substituted heterocycloalkyl. In some embodiments, R8Bmay be unsubstituted heterocycloalkyl. In some embodiments. R8Bmay be substituted aryl. In some embodiments, R8Bmay be unsubstituted aryl. In some embodiments, R8Bmay be substituted heteroaryl. In some embodiments, R8Bmay be unsubstituted heteroaryl.

[0271] In some embodiments, R8may be -N(O)m8wherein m8 may be an integer from 1 to 2 (e.g., -N(O), -NO2).

[0272] In some embodiments, R8may be -NR8AR8B. In some embodiments, R8Amay be hydrogen. In some embodiments, R8Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R8Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI2). In some embodiments, R8Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R8Amay be -COOH. In some embodiments, R8Amay be substituted alkyl. In some embodiments, R8Amay be unsubstituted alkyl. In some embodiments, R8Amay be substituted heteroalkyl. In some embodiments, R8Amay be unsubstituted heteroalkyl. In some embodiments, R8Amay be substituted cycloalkyl. In some embodiments, R8Amay be unsubstituted cycloalkyl. In some embodiments, R8Amay be substituted heterocycloalkyl. In some embodiments, R8Amay be unsubstituted heterocycloalkyl. In some embodiments, R8Amay be substituted aryl. In some embodiments, R8Amay be unsubstituted aryl. In some embodiments, R8Amay be substituted heteroaryl. In some embodiments, R8Amay be unsubstituted heteroaryl. In some embodiments, R8Bmay be hydrogen. In some embodiments, R8Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Bmay be -CX3, (e.g., -CF₃, -CCl3, -CBr₃, -CI₃). In some embodiments, R8Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI₂). In some embodiments, R8Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R8Dmay be -COOH. In some embodiments, R8Dmay be substituted alkyl. In some embodiments, R8Bmay be unsubstituted alkyl. In some embodiments, R8Bmay be substituted heteroalkyl. In some embodiments, R8Bmay be unsubstituted heteroalkyl. In some embodiments, R8Bmay be substituted cycloalkyl. In some embodiments, R8Bmay be unsubstituted cycloalkyl. In some embodiments. R8Bmay be substituted heterocycloalkyl. In some embodiments, R8Bmay be unsubstituted heterocycloalkyl. In some embodiments, R8Bmay be substituted aryl. In some embodiments, R8Bmay be unsubstituted aryl. In some embodiments, R8Bmay be substituted heteroaryl. In some embodiments, R8Bmay be unsubstituted heteroaryl.

[0273] In some embodiments, R8may be -C(O)R8C. In some embodiments, R8Cmay be hydrogen. In some embodiments, R8Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R8Cmay be -CHX2, (e g., -CHF2, -CHCk, -CHBr₂, -CHI₂). In some embodiments, R8Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R8Cmay be -COOH. In some embodiments, R8Cmay be substituted alkyl. In some embodiments, R8Cmay be unsubstituted alkyl. In some embodiments, R8Cmay be substituted heteroalkyl. In some embodiments, R8Cmay be unsubstituted heteroalkyl. In some embodiments, R8Cmay be substituted cycloalkyl. In some embodiments, R8Cmay be unsubstituted cycloalkyl. In some embodiments, R8Cmay be substituted heterocycloalkyl. In some embodiments, R8Cmay be unsubstituted heterocycloalkyl. In some embodiments, R8Cmay be substituted ai I. In some embodiments, R8Cmay be unsubstituted aryl. In some embodiments, R8Cmay be substituted heteroaryl. In some embodiments, R8Cmay be unsubstituted heteroaryl.

[0274] In some embodiments, R8may be -C(O)-OR8C. In some embodiments, R8Cmay be hydrogen. In some embodiments, R8Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R8Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R8Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R8Cmay be -COOH. In some embodiments, R8Cmay be substituted alkyl. In some embodiments, R8Cmay be unsubstituted alkyl. In some embodiments, R8Cmay be substituted heteroalkyl. In some embodiments, R8Cmay be unsubstituted heteroalkyl. In some embodiments, R8Cmay be substituted cycloalkyl. In some embodiments, R8Cmay be unsubstituted cycloalkyl. In some embodiments, R8Cmay be substituted heterocycloalkyl. In some embodiments, R8Cmay be unsubstituted heterocycloalkyl. In some embodiments, R8Cmay be substituted aryl. In some embodiments, R8Cmay be unsubstituted aryl. In some embodiments, R8Cmay be substituted heteroaryl. In some embodiments, R8Cmay be unsubstituted heteroaryl.

[0275] In some embodiments, R8may be -C(O)NR8AR8B. In some embodiments, R8Amay be hydrogen. In some embodiments, R8Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R8Amay be -CHX2. (e.g.. -CHF2. -CHCh, -CHBr2, -CHI₂). In some embodiments, R8Amay be -CH2X, (e.g., -CH2F, -CH₂Cl, -QhBr, -CH2I). In some embodiments, R8Amay be -COOH. In some embodiments, R8Amay be substituted alkyl. In some embodiments, R8Amay be unsubstituted alkyl. In some embodiments, R8Amay be substituted heteroalkyl. In some embodiments, R8Amay be unsubstituted heteroalkyl. In some embodiments, R8Amay besubstituted cycloalkyl. In some embodiments, R8Amay be unsubstituted cycloalkyl. In some embodiments, R8Amay be substituted heterocycloalkyl. In some embodiments, R8Amay be unsubstituted heterocycloalkyl. In some embodiments, R8Amay be substituted aryl. In some embodiments, R8Amay be unsubstituted aryl. In some embodiments, R8Amay be substituted heteroaryl. In some embodiments, R8Amay be unsubstituted heteroaryl. In some embodiments, R8Bmay be hydrogen. In some embodiments, R8Bmay be halogen, (e.g., -F, -Br, -Cl. -I). In some embodiments. R8Bmay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R8Bmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R8Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R8Bmay be -COOH. In some embodiments, R8Bmay be substituted alkyl. In some embodiments, R8Bmay be unsubstituted alkyl. In some embodiments. R8Bmay be substituted heteroalkyl. In some embodiments, R8Bmay be unsubstituted heteroalkyl. In some embodiments, R8Bmay be substituted cycloalkyl. In some embodiments, R8Bmay be unsubstituted cycloalkyl. In some embodiments, R8Bmay be substituted heterocycloalkyl. In some embodiments, R8Bmay be unsubstituted heterocycloalkyl. In some embodiments. R8Bmay be substituted aryl. In some embodiments, R8Dmay be unsubstituted aryl. In some embodiments, R8Bmay be substituted heteroaryl. In some embodiments, R8Bmay be unsubstituted heteroaryl.

[0276] In some embodiments, R8may be -OR8D. In some embodiments, R8Dmay be hydrogen. In some embodiments, R8Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Dmay be -CX3. (e.g.. -CF3. -CCl3, -CBr₃, -CI₃). In some embodiments, R8Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI2). In some embodiments, R8Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R8Dmay be -COOH. In some embodiments, R8Dmay be substituted alkyl. In some embodiments, R8Dmay be unsubstituted alkyl. In some embodiments, R8Dmay be substituted heteroalkyl. In some embodiments, R8Dmay be unsubstituted heteroalkyl. In some embodiments, R8Dmay be substituted cycloalkyl. In some embodiments, R8Dmay be unsubstituted cycloalkyl. In some embodiments, R8Dmay be substituted heterocycloalkyl. In some embodiments, R8Dmay be unsubstituted heterocycloalkyl. In some embodiments, R8Dmay be substituted aryl. In some embodiments, R8Dmay be unsubstituted aryl. In some embodiments, R8Dmay be substituted heteroaryl. In some embodiments, R8Dmay be unsubstituted heteroaryl.

[0277] In some embodiments, R8may be -NR8ASO2R8D. In some embodiments, R8Amay be hydrogen. In some embodiments, R8Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R8Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R8Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R8Amay be -COOH. In some embodiments, R8Amay be substituted alkyl. In some embodiments, R8Amay be unsubstituted alkyl. In some embodiments, R8Amay be substituted heteroalkyl. In some embodiments, R8Amay be unsubstituted heteroalkyl. In some embodiments, R8Amay be substituted cycloalkyl. In some embodiments, R8Amay be unsubstituted cycloalkyl. In some embodiments, R8Amay be substituted heterocycloalkyl. In some embodiments, R8Amay be unsubstituted heterocycloalkyl. In some embodiments, R8Amay be substituted aryl. In some embodiments, R8Amay be unsubstituted aryl. In some embodiments, R8Amay be substituted heteroaryl. In some embodiments, R8Amay be unsubstituted heteroaryl. In some embodiments, R8Dmay be hydrogen. In some embodiments, R8Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Dmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R8Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R8Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R8Dmay be -COOH. In some embodiments, R8Dmay be substituted alkyl. In some embodiments, R8Dmay be unsubstituted alkyl. In some embodiments, R8Dmay be substituted heteroalkyl. In some embodiments, R8Dmay be unsubstituted heteroalkyl. In some embodiments, R8Dmay be substituted cycloalkyl. In some embodiments, R8Dmay be unsubstituted cycloalkyl. In some embodiments, R8Dmay be substituted heterocycloalkyl. In some embodiments, R8Dmay be unsubstituted heterocycloalkyl. In some embodiments, R8Dmay be substituted aryl. In some embodiments, R8Dmay be unsubstituted aryl. In some embodiments, R8Dmay be substituted heteroaryl. In some embodiments, R8Dmay be unsubstituted heteroaryl.

[0278] In some embodiments, R8may be -NR8AC(O)R8C. In some embodiments, R8Amay be hydrogen. In some embodiments, R8Amay be halogen, (e.g., -F, -Br. -Cl, -I). In some embodiments, R8Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R8Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R8Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R8Amay be -COOH. In some embodiments, R8Amay be substituted alkyl. In some embodiments, R8Amay be unsubstituted alkyl. In some embodiments, R8Amay be substituted heteroalkyl. In some embodiments, R8Amay be unsubstituted heteroalkyl. In some embodiments, R8Amay be substituted cycloalkyl. In some embodiments, R8Amay be unsubstituted cycloalkyl. In some embodiments, R8Amay be substituted heterocycloalkyl. In some embodiments, R8Amay be unsubstituted heterocycloalkyl. In some embodiments, R8Amay be substituted aryl. In someembodiments, R8Amay be unsubstituted aryl. In some embodiments, R8Amay be substituted heteroaryl. In some embodiments, R8Amay be unsubstituted heteroaryl. In some embodiments, R8Cmay be hydrogen. In some embodiments, R8Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Cmay be -CX₃, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R8Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R8Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R8Cmay be -COOH. In some embodiments, R8Cmay be substituted alkyl. In some embodiments, R8Cmay be unsubstituted alkyl. In some embodiments, R8Cmay be substituted heteroalkyl. In some embodiments, R8Cmay be unsubstituted heteroalkyl. In some embodiments, R8Cmay be substituted cycloalkyl. In some embodiments, R8Cmay be unsubstituted cycloalkyl. In some embodiments, R8Cmay be substituted heterocycloalkyl. In some embodiments, R8Cmay be unsubstituted heterocycloalkyl. In some embodiments, R8Cmay be substituted aryl. In some embodiments, R8Cmay be unsubstituted aryl. In some embodiments, R8Cmay be substituted heteroaryl. In some embodiments, R8Cmay be unsubstituted heteroaryl.

[0279] In some embodiments, R8may be -NR8AC(O)OR8C. In some embodiments, R8Amay be hydrogen. In some embodiments, R8Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R8Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R8Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R8Amay be -COOH. In some embodiments, R8Amay be substituted alkyl. In some embodiments. R8Amay be unsubstituted alkyl. In some embodiments, R8Amay be substituted heteroalkyl. In some embodiments, R8Amay be unsubstituted heteroalkyl. In some embodiments, R8Amay be substituted cycloalkyl. In some embodiments, R8Amay be unsubstituted cycloalkyl. In some embodiments, R8Amay be substituted heterocycloalkyl. In some embodiments, R8Amay be unsubstituted heterocycloalkyl. In some embodiments, R8Amay be substituted aryl. In some embodiments, R8Amay be unsubstituted aryl. In some embodiments, R8Amay be substituted heteroaryl. In some embodiments, R8Amay be unsubstituted heteroaryl. In some embodiments, R8Cmay be hydrogen. In some embodiments, R8Cmay be halogen, (e.g.. -F, -Br, -Cl. -I). In some embodiments. R8Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R8Cmay' be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI2). In some embodiments, R8Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R8Cmay be -COOH. In some embodiments, R8Cmay be substituted alkyl. In some embodiments, R8Cmay be unsubstituted alkyl. In some embodiments. R8Cmay besubstituted heteroalkyl. In some embodiments, R8Cmay be unsubstituted heteroalkyl. In some embodiments, R8Cmay be substituted cycloalkyl. In some embodiments, R8Cmay be unsubstituted cycloalkyl. In some embodiments. R8Cmay be substituted heterocycloalkyl. In some embodiments, R8Cmay be unsubstituted heterocycloalkyl. In some embodiments, R8Cmay be substituted aryl. In some embodiments, R8Cmay be unsubstituted aryl. In some embodiments, R8Cmay be substituted heteroaryl. In some embodiments, R8Cmay be unsubstituted heteroaryl.

[0280] In some embodiments, R8may be -NR8AOR8C. In some embodiments, R8Amay be hydrogen. In some embodiments, R8Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R8Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R8Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R8Amay be -CH2X, (e g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments, R8Amay be -COOH. In some embodiments, R8Amay be substituted alkyl. In some embodiments, R8Amay be unsubstituted alkyl. In some embodiments, R8Amay be substituted heteroalkyl. In some embodiments, R8Amay be unsubstituted heteroalkyl. In some embodiments, R8Amay be substituted cycloalkyl. In some embodiments, R8Amay be unsubstituted cycloalkyl. In some embodiments, R8Amay be substituted heterocycloalkyl. In some embodiments, R8Amay be unsubstituted heterocycloalkyl. In some embodiments, R8Amay be substituted aryl. In some embodiments, R8Amay be unsubstituted aryl. In some embodiments, R8Amay be substituted heteroaryl. In some embodiments, R8Amay be unsubstituted heteroaryl. In some embodiments, R8Cmay be hydrogen. In some embodiments, R8Cmay be halogen, (e.g.. -F. -Br, -Cl, -I). In some embodiments, R8Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R8Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R8Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R8Cmay be -COOH. In some embodiments, R8Cmay be substituted alkyl. In some embodiments, R8Cmay be unsubstituted alkyl. In some embodiments, R8Cmay be substituted heteroalkyl. In some embodiments, R8Cmay be unsubstituted heteroalkyl. In some embodiments, R8Cmay be substituted cycloalkyl. In some embodiments, R8Cmay be unsubstituted cycloalkyl. In some embodiments, R8Cmay be substituted heterocycloalkyl. In some embodiments, R8Cmay be unsubstituted heterocycloalkyl. In some embodiments, R8Cmay be substituted aryl. In some embodiments, R8Cmay be unsubstituted aryl. In some embodiments, R8Cmay be substituted heteroaryl. In some embodiments, R8Cmay be unsubstituted heteroaryl.

[0281] In some embodiments, R8may be substituted alkyl. In some embodiments, R8may be unsubstituted alkyl. In some embodiments, R8may be substituted heteroalkyl. In some embodiments, R8may be unsubstituted heteroalkyl. In some embodiments, R8may be substituted cycloalkyl. In some embodiments, R8may be unsubstituted cycloalkyl. In some embodiments, R8may be substituted heterocycloalkyl. In some embodiments, R8may be unsubstituted heterocycloalkyl. In some embodiments, R8may be substituted aryl. In some embodiments, R8may be unsubstituted aryl. In some embodiments, R8may be substituted heteroaryl. In some embodiments, R8may be unsubstituted heteroaryl.

[0282] In some embodiments, R9may be absent. In some embodiments, R9may be hydrogen. In some embodiments, R9may be halogen. In some embodiments, R9may be -CX93, (e.g., CF3, CCI3, CBn, CI3). In some embodiments, R9may be -CHX92, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments. R9may be -CH2X9, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R9may be -OCX93, (e.g., -OCF3, -OCCI3, -OCBr₃, -OCI3). In some embodiments, R9may be -OCHX92, (e.g., -OCHF2, -OCHCI2, -OCHBr₂, -OCHI2). In some embodiments, R9may be -OCH2X9, (e g., -OCH2F, -OCH2CI, -OCH₂Br, -OCH2I). In some embodiments, R9may be -OCH3.

[0283] In some embodiments, R9may be -OCH2R9A. In some embodiments, R9Amay be hydrogen. In some embodiments, R9Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R9Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr2, -CHI2). In some embodiments, R9Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R9Amay be -COOH. In some embodiments, R9Amay be substituted alkyl. In some embodiments, R9Amay be unsubstituted alkyl. In some embodiments, R9Amay be substituted heteroalkyl. In some embodiments, R9Amay be unsubstituted heteroalkyl. In some embodiments, R9Amay be substituted cycloalkyl. In some embodiments, R9Amay be unsubstituted cycloalkyl. In some embodiments, R9Amay be substituted heterocycloalkyl. In some embodiments, R9Amay be unsubstituted heterocycloalkyl. In some embodiments, R9Amay be substituted aryl. In some embodiments, R9Amay be unsubstituted aryl. In some embodiments, R9Amay be substituted heteroaryl. In some embodiments, R9Amay be unsubstituted heteroaryl.

[0284] In some embodiments, R9may be -N₃, -CN.

[0285] In some embodiments, R9may be -SOn9R9Dwhereinn9 may be an integer from 0 - 4 (e.g., -S-, -SO-, -SO2-, -SO3-, -SO4-). In some embodiments, R9Dmay be hydrogen. In some embodiments, R9Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Dmay be-CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R9Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R9Dmay be -CH2X, (e.g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments, R9Dmay be -COOH. In some embodiments, R9Dmay be substituted alkyl. In some embodiments, R9Dmay be unsubstituted alkyl. In some embodiments, R9Dmay be substituted heteroalkyl. In some embodiments, R9Dmay be unsubstituted heteroalkyl. In some embodiments, R9Dmay be substituted cycloalkyl. In some embodiments, R9Dmay be unsubstituted cycloalkyl. In some embodiments. R9Dmay be substituted heterocycloalkyl. In some embodiments, R9Dmay be unsubstituted heterocycloalkyl. In some embodiments, R9Dmay be substituted aryl. In some embodiments, R9Dmay be unsubstituted aryl. In some embodiments, R9Dmay be substituted heteroaryl. In some embodiments, R9Dmay be unsubstituted heteroaryl.

[0286] In some embodiments, R9may be -SOv9NR9AR9BwhereinV9 may be an integer from 1 to 2 (e.g., -SON-, -SO2N-). In some embodiments, R9Amay be hydrogen. In some embodiments, R9Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R9Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R9Amay be -CH2X, (e.g., -CH2F, -CH₂Cl, -CH2Br, -CH2I). In some embodiments, R9Amay be -COOH. In some embodiments, R9Amay be substituted alkyl. In some embodiments, R9Amay be unsubstituted alkyl. In some embodiments, R9Amay be substituted heteroalkyl. In some embodiments, R9Amay be unsubstituted heteroalkyl. In some embodiments, R9Amay be substituted cycloalkyl. In some embodiments, R9Amay be unsubstituted cycloalkyl. In some embodiments. R9Amay be substituted heterocycloalkyl. In some embodiments, R9Amay be unsubstituted heterocycloalkyl. In some embodiments, R9Amay be substituted aryl. In some embodiments, R9Amay be unsubstituted aryl. In some embodiments, R9Amay be substituted heteroaryl. In some embodiments, R9Amay be unsubstituted heteroaryl. In some embodiments, R9Bmay be hydrogen. In some embodiments, R9Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Bmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R9Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R9Bmay be -CH2X, (e g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R9Bmay be -COOH. In some embodiments, R9Bmay be substituted alkyl. In some embodiments, R9Bmay be unsubstituted alkyl. In some embodiments, R9Bmay be substituted heteroalkyl. In some embodiments, R9Bmay be unsubstituted heteroalkyl. In some embodiments, R9Bmay be substituted cycloalkyl. In some embodiments, R9Bmay be unsubstituted cycloalkyl. In some embodiments, R9Bmay be substituted heterocycloalkyl. In some embodiments, R9Bmay beunsubstituted heterocycloalkyl. In some embodiments, R9Bmay be substituted aryl. In some embodiments, R9Bmay be unsubstituted aryl. In some embodiments, R9Bmay be substituted heteroaryl. In some embodiments, R9Bmay be unsubstituted heteroaryl.

[0287] In some embodiments, R9may be -NHC(O)NR9AR9B. In some embodiments, R9Amay be hydrogen. In some embodiments, R9Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R9Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI2). In some embodiments, R9Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R9Amay be -COOH. In some embodiments, R9Amay be substituted alkyl. In some embodiments, R9Amay be unsubstituted alkyl. In some embodiments, R9Amay be substituted heteroalkyl. In some embodiments, R9Amay be unsubstituted heteroalkyl. In some embodiments, R9Amay be substituted cycloalkyl. In some embodiments, R9Amay be unsubstituted cycloalkyl. In some embodiments, R9Amay be substituted heterocycloalkyl. In some embodiments, R9Amay be unsubstituted heterocycloalkyl. In some embodiments, R9Amay be substituted aryl. In some embodiments, R9Amay be unsubstituted aryl. In some embodiments, R9Amay be substituted heteroaryl. In some embodiments, R9Amay be unsubstituted heteroaryl. In some embodiments, R9Bmay be hydrogen. In some embodiments, R9Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Bmay be -CX3, (e.g., -CF₃, -CCl3, -CBr₃, -CI₃). In some embodiments, R9Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R9Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R9Dmay be -COOH. In some embodiments, R9Bmay be substituted alkyl. In some embodiments, R9Bmay be unsubstituted alkyl. In some embodiments, R9Bmay be substituted heteroalkyl. In some embodiments, R9Bmay be unsubstituted heteroalkyl. In some embodiments, R9Bmay be substituted cycloalkyl. In some embodiments, R9Bmay be unsubstituted cycloalkyl. In some embodiments. R9Bmay be substituted heterocycloalkyl. In some embodiments, R9Bmay be unsubstituted heterocycloalkyl. In some embodiments, R9Bmay be substituted aryl. In some embodiments, R9Bmay be unsubstituted aryl. In some embodiments, R9Bmay be substituted heteroaryl. In some embodiments, R9Bmay be unsubstituted heteroaryl.

[0288] In some embodiments, R9may be -N(O)m9whereinm9 may be an integer from 1 to 2 (e.g., -N(O), -NO2).

[0289] In some embodiments, R9may be -NR9AR9B. In some embodiments, R9Amay be hydrogen. In some embodiments, R9Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Amay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R9Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R9Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R9Amay be -COOH. In some embodiments, R9Amay be substituted alkyl. In some embodiments, R9Amay be unsubstituted alkyl. In some embodiments, R9Amay be substituted heteroalkyl. In some embodiments, R9Amay be unsubstituted heteroalkyl. In some embodiments, R9Amay be substituted cycloalkyl. In some embodiments, R9Amay be unsubstituted cycloalkyl. In some embodiments, R9Amay be substituted heterocycloalkyl. In some embodiments, R9Amay be unsubstituted heterocycloalkyl. In some embodiments, R9Amay be substituted aryl. In some embodiments, R9Amay be unsubstituted aryl. In some embodiments, R9Amay be substituted heteroaryl. In some embodiments, R9Amay be unsubstituted heteroaryl. In some embodiments, R9Bmay be hydrogen. In some embodiments, R9Bmay be halogen, (e.g.. -F, -Br, -Cl, -I). In some embodiments, R9Bmay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R9Bmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R9Bmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R9Bmay be -COOH. In some embodiments, R9Bmay be substituted alkyl. In some embodiments, R9Bmay be unsubstituted alkyl. In some embodiments. R9Dmay be substituted heteroalkyl. In some embodiments, R9Bmay be unsubstituted heteroalkyl. In some embodiments, R9Bmay be substituted cycloalkyl. In some embodiments, R9Bmay be unsubstituted cycloalkyl. In some embodiments, R9Bmay be substituted heterocycloalkyl. In some embodiments, R9Bmay be unsubstituted heterocycloalkyl. In some embodiments. R9Bmay be substituted aryl. In some embodiments, R9Bmay be unsubstituted aryl. In some embodiments, R9Bmay be substituted heteroaryl. In some embodiments, R9Bmay be unsubstituted heteroaryl.

[0290] In some embodiments, R9may be -C(O)R9C. In some embodiments, R9Cmay be hydrogen. In some embodiments, R9Cmay be halogen, (e.g., -F. -Br, -Cl, -I). In some embodiments, R9Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R9Cmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI₂). In some embodiments, R9Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R9Cmay be -COOH. In some embodiments, R9Cmay be substituted alkyl. In some embodiments, R9Cmay be unsubstituted alkyl. In some embodiments, R9Cmay be substituted heteroalkyl. In some embodiments, R9Cmay be unsubstituted heteroalkyl. In some embodiments, R9Cmay be substituted cycloalkyl. In some embodiments, R9Cmay be unsubstituted cycloalkyl. In some embodiments, R9Cmay be substituted heterocycloalkyl. In some embodiments, R9Cmay be unsubstituted heterocycloalkyl. In some embodiments, R9Cmay be substituted aryl. In someembodiments, R9Cmay be unsubstituted aryl. In some embodiments, R9Cmay be substituted heteroaryl. In some embodiments, R9Cmay be unsubstituted heteroaryl.

[0291] In some embodiments, R9may be -C(O)-OR9C. In some embodiments, R9Cmay be hydrogen. In some embodiments, R9Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R9Cmay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI2). In some embodiments, R9Cmay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R9Cmay be -COOH. In some embodiments, R9Cmay be substituted alkyl. In some embodiments, R9Cmay be unsubstituted alkyl. In some embodiments, R9Cmay be substituted heteroalkyl. In some embodiments, R9Cmay be unsubstituted heteroalkyl. In some embodiments, R9Cmay be substituted cycloalkyl. In some embodiments, R9Cmay be unsubstituted cycloalkyl. In some embodiments, R9Cmay be substituted heterocycloalkyl. In some embodiments, R9Cmay be unsubstituted heterocycloalkyl. In some embodiments, R9Cmay be substituted aryl. In some embodiments, R9Cmay be unsubstituted aryl. In some embodiments, R9Cmay be substituted heteroaryl. In some embodiments, R9Cmay be unsubstituted heteroaryl.

[0292] In some embodiments, R9may be -C(O)NR9AR9B. In some embodiments, R9Amay be hydrogen. In some embodiments, R9Amay be halogen, (e.g., -F, -Br. -Cl, -I). In some embodiments, R9Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R9Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R9Amay be -CH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R9Amay be -COOH. In some embodiments, R9Amay be substituted alkyl. In some embodiments, R9Amay be unsubstituted alkyl. In some embodiments, R9Amay be substituted heteroalkyl. In some embodiments, R9Amay be unsubstituted heteroalkyl. In some embodiments, R9Amay be substituted cycloalkyl. In some embodiments, R9Amay be unsubstituted cycloalkyl. In some embodiments, R9Amay be substituted heterocycloalkyl. In some embodiments, R9Amay be unsubstituted heterocycloalkyl. In some embodiments, R9Amay be substituted aryl. In some embodiments, R9Amay be unsubstituted aryl. In some embodiments, R9Amay be substituted heteroaryl. In some embodiments, R9Amay be unsubstituted heteroaryl. In some embodiments, R9Bmay be hydrogen. In some embodiments, R9Bmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Bmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R9Bmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R9Bmay be -CH2X, (e.g., -CH2F, -CH₂Cl, -CH2Br, -CH2I). In some embodiments, R9Bmay be -COOH. In some embodiments, R9Bmay be substituted alkyl. In some embodiments, R9Bmay be unsubstituted alkyl. In some embodiments. R9Bmay besubstituted heteroalkyl. In some embodiments, R9Bmay be unsubstituted heteroalkyl. In some embodiments, R9Bmay be substituted cycloalkyl. In some embodiments, R9Bmay be unsubstituted cycloalkyl. In some embodiments. R9Bmay be substituted heterocycloalkyl. In some embodiments, R9Bmay be unsubstituted heterocycloalkyl. In some embodiments, R9Bmay be substituted aryl. In some embodiments, R9Bmay be unsubstituted aryl. In some embodiments, R9Bmay be substituted heteroaryl. In some embodiments, R9Bmay be unsubstituted heteroaryl.

[0293] In some embodiments, R9may be -OR9D. In some embodiments, R9Dmay be hydrogen. In some embodiments, R9Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Dmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R9Dmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R9Dmay be -CH2X, (e g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments, R9Dmay be -COOH. In some embodiments, R9Dmay be substituted alkyl. In some embodiments, R9Dmay be unsubstituted alkyl. In some embodiments, R9Dmay be substituted heteroalkyl. In some embodiments, R9Dmay be unsubstituted heteroalkyl. In some embodiments, R9Dmay be substituted cycloalkyl. In some embodiments, R9Dmay be unsubstituted cycloalkyl. In some embodiments, R9Dmay be substituted heterocycloalkyl. In some embodiments, R9Dmay be unsubstituted heterocycloalkyl. In some embodiments, R9Dmay be substituted aryl. In some embodiments, R9Dmay be unsubstituted aryl. In some embodiments, R9Dmay be substituted heteroaryl. In some embodiments, R9Dmay be unsubstituted heteroaryl.

[0294] In some embodiments, R9may be -NR9ASO2R9D. In some embodiments, R9Amay be hydrogen. In some embodiments, R9Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Amay be -CX₃, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R9Amay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI₂). In some embodiments, R9Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R9Amay be -COOH. In some embodiments, R9Amay be substituted alkyl. In some embodiments. R9Amay be unsubstituted alkyl. In some embodiments, R9Amay be substituted heteroalkyl. In some embodiments, R9Amay be unsubstituted heteroalkyl. In some embodiments, R9Amay be substituted cycloalkyl. In some embodiments, R9Amay be unsubstituted cycloalkyl. In some embodiments, R9Amay be substituted heterocycloalkyl. In some embodiments, R9Amay be unsubstituted heterocycloalkyl. In some embodiments, R9Amay be substituted aryl. In some embodiments, R9Amay be unsubstituted aryl. In some embodiments, R9Amay be substituted heteroaryl. In some embodiments, R9Amay be unsubstituted heteroaryl. In some embodiments, R9Dmay be hydrogen. In some embodiments, R9Dmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Dmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R9Dmay be -CHX2, (e.g., -CHF2, -CHCl₂, -CHBr₂, -CHI2). In some embodiments, R9Dmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R9Dmay be -COOH. In some embodiments, R9Dmay be substituted alkyl. In some embodiments, R9Dmay be unsubstituted alkyl. In some embodiments, R9Dmay be substituted heteroalkyl. In some embodiments. R9Dmay be unsubstituted heteroalkyl. In some embodiments, R9Dmay be substituted cycloalkyl. In some embodiments, R9Dmay be unsubstituted cycloalkyl. In some embodiments, R9Dmay be substituted heterocycloalkyl. In some embodiments, R9Dmay be unsubstituted heterocycloalkyl. In some embodiments, R9Dmay be substituted aryl. In some embodiments, R9Dmay be unsubstituted aryl. In some embodiments, R9Dmay be substituted heteroaryl. In some embodiments, R9Dmay be unsubstituted heteroaryl.

[0295] In some embodiments, R9may be -NR9AC(O)R9CIn some embodiments, R9Amay be hydrogen. In some embodiments, R9Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R9Amay be -CHX2. (e.g., -CHF2, -CHCl₂, -CHBr2, -CHI2). In some embodiments, R9Amay be -CH2X, (e g., -CH2F, -CH₂Cl, -CH₂Br, -CH2I). In some embodiments. R9Amay be -COOH. In some embodiments, R9Amay be substituted alkyl. In some embodiments, R9Amay be unsubstituted alkyl. In some embodiments, R9Amay be substituted heteroalkyl. In some embodiments, R9Amay be unsubstituted heteroalkyl. In some embodiments, R9Amay be substituted cycloalkyl. In some embodiments, R9Amay be unsubstituted cycloalkyl. In some embodiments, R9Amay be substituted heterocycloalkyl. In some embodiments, R9Amay be unsubstituted heterocycloalkyl. In some embodiments, R9Amay be substituted aryl. In some embodiments, R9Amay be unsubstituted aryl. In some embodiments, R9Amay be substituted heteroaryl. In some embodiments, R9Amay be unsubstituted heteroaryl. In some embodiments, R9Cmay be hydrogen. In some embodiments, R9Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Cmay be -CX3, (e.g., -CF₃, -CCl3, -CBr₃, -CI₃). In some embodiments, R9Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R9Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br, -CH2I). In some embodiments, R9Cmay be -COOH. In some embodiments, R9Cmay be substituted alkyl. In some embodiments, R9Cmay be unsubstituted alkyl. In some embodiments, R9Cmay be substituted heteroalkyl. In some embodiments, R9Cmay be unsubstituted heteroalkyl. In some embodiments, R9Cmay be substituted cycloalkyl. In some embodiments, R9Cmay be unsubstituted cycloalkyl. In some embodiments. R9Cmay be substituted heterocycloalkyl. Insome embodiments, R9Cmay be unsubstituted heterocycloalkyl. In some embodiments, R9Cmay be substituted aryl. In some embodiments, R9Cmay be unsubstituted aryl. In some embodiments, R9Cmay be substituted heteroaryl. In some embodiments, R9Cmay be unsubstituted heteroaryl.

[0296] In some embodiments, R9may be -NR9AC(O)OR9C. In some embodiments, R9Amay be hydrogen. In some embodiments, R9Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Amay be -CX3, (e.g., -CF₃, -CCl₃, -CBr₃, -CI₃). In some embodiments, R9Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI2). In some embodiments, R9Amay be -CH2X, (e g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R9Amay be -COOH. In some embodiments, R9Amay be substituted alkyl. In some embodiments, R9Amay be unsubstituted alkyl. In some embodiments, R9Amay be substituted heteroalkyl. In some embodiments, R9Amay be unsubstituted heteroalkyl. In some embodiments, R9Amay be substituted cycloalkyl. In some embodiments, R9Amay be unsubstituted cycloalkyl. In some embodiments, R9Amay be substituted heterocycloalkyl. In some embodiments, R9Amay be unsubstituted heterocycloalkyl. In some embodiments, R9Amay be substituted aryl. In some embodiments, R9Amay be unsubstituted aryl. In some embodiments, R9Amay be substituted heteroaryl. In some embodiments, R9Amay be unsubstituted heteroaryl. In some embodiments, R9Cmay be hydrogen. In some embodiments, R9Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Cmay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R9Cmay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr₂, -CHI₂). In some embodiments, R9Cmay be -CH2X, (e.g., -CH2F, -CH2CI, -CH2Br. -CH2I). In some embodiments, R9Cmay be -COOH. In some embodiments, R9Cmay be substituted alkyl. In some embodiments, R9Cmay be unsubstituted alkyl. In some embodiments, R9Cmay be substituted heteroalkyl. In some embodiments, R9Cmay be unsubstituted heteroalkyl. In some embodiments, R9Cmay be substituted cycloalkyl. In some embodiments, R9Cmay be unsubstituted cycloalkyl. In some embodiments, R9Cmay be substituted heterocycloalkyl. In some embodiments, R9Cmay be unsubstituted heterocycloalkyl. In some embodiments, R9Cmay be substituted aryl. In some embodiments, R9Cmay be unsubstituted aryl. In some embodiments, R9Cmay be substituted heteroaryl. In some embodiments, R9Cmay be unsubstituted heteroaryl.

[0297] In some embodiments, R9may be -NR9AOR9C. In some embodiments, R9Amay be hydrogen. In some embodiments, R9Amay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Amay be -CX3, (e.g., -CF3, -CCl3, -CBr₃, -CI₃). In some embodiments, R9Amay be -CHX2, (e.g., -CHF2, -CHCh, -CHBr2, -CHI₂). In some embodiments, R9Amay be - I llCH2X, (e.g., -CH2F, -CH2CI, -CH₂Br, -CH2I). In some embodiments, R9Amay be -COOH. In some embodiments, R9Amay be substituted alkyl. In some embodiments, R9Amay be unsubstituted alkyl. In some embodiments, R9Amay be substituted heteroalkyl. In some embodiments, R9Amay be unsubstituted heteroalkyl. In some embodiments, R9Amay be substituted cycloalkyl. In some embodiments, R9Amay be unsubstituted cycloalkyl. In some embodiments, R9Amay be substituted heterocycloalkyl. In some embodiments, R9Amay be unsubstituted heterocycloalkyl. In some embodiments, R9Amay be substituted aryl. In some embodiments, R9Amay be unsubstituted aryl. In some embodiments, R9Amay be substituted heteroaryl. In some embodiments, R9Amay be unsubstituted heteroaryl. In some embodiments, R9Cmay be hydrogen. In some embodiments, R9Cmay be halogen, (e.g., -F, -Br, -Cl, -I). In some embodiments, R9Cmay be -CX3, (e.g., -CF3, -CCl₃, -CBr₃, -CI₃). In some embodiments, R9Cmay be -CHX2, (e.g., -CHF2, -CHCI2, -CHBr₂, -CHI2). In some embodiments, R9Cmay be -CH2X, (e.g., -CH2F, -CH₂Cl, -CH2Br, -CH2I). In some embodiments, R9Cmay be -COOH. In some embodiments, R9Cmay be substituted alkyl. In some embodiments, R9Cmay be unsubstituted alkyl. In some embodiments. R9Cmay be substituted heteroalkyl. In some embodiments. R9Cmay be unsubstituted heteroalkyl. In some embodiments, R9Cmay be substituted cycloalkyl. In some embodiments, R9Cmay be unsubstituted cycloalkyl. In some embodiments, R9Cmay be substituted heterocycloalkyl. In some embodiments, R9Cmay be unsubstituted heterocycloalkyl. In some embodiments, R9Cmay be substituted aryl. In some embodiments, R9Cmay be unsubs...

Claims

Attorney Docket No.: 0G2440- 1532676 (095WO1) WHAT IS CLAIMED IS:

1. A method of inhibiting an increase in potassium channel activity in a subject in need thereof, comprising:administering an effective amount of a small molecule inhibitor that selectively binds to a Per-Arnt-Sim (PAS) domain of Ether-a-go-go 1 (EAG1) potassium channels to a subject having a disorder associated with increased potassium channel activity;wherein the small molecule inhibitor comprises a polycyclic compound containing rings;wherein at least one of the rings is unsaturated and;wherein at least one of the rings has a pendent substituent.

2. The method of claim 1, wherein the small molecule inhibitor comprises a compound represented by Formula (I):R2wherein:L1is a bond toL1A, -SOmiL1A-, -SOv11NR11L1A-, -NHC(O)NR" LI A-, - NRnL1A-, -C(O)L1A-, -C(O)OL1A-, -C(O)NRnL1A-, -OL1A-, -NR11SO2L1A-, NRnC(O)L1A-, -NRnC(O)OL1A-, NRnOL1A, -SL1A-, -substituted alkyl -L1A-, - unsubstituted alkyl-L1A-, -substituted heteroalkyl-LIA-, -unsubstituted heteroalkyl-L1A-, - substituted alkylene-L1A-, -unsubstituted alkylene-L1A-, -substituted heteroalkylene-L1A-, -unsubstituted heteroalkylene-L1A-, -substituted cycloalkylene-L1A-, -unsubstituted cycloalkylene-L1A-, -substituted heterocycloalkylene-L1A-, -unsubstituted heterocycloalkylene-L1A-, -un substituted arylene-L1A-, -unsubstituted arylene-L1A-, - substituted heteroarylene-L1A-, or -unsubstituted heteroarylene-L1A-;R1is independently absent, hydrogen, halogen, -CXh, -CHX^, -CH2X1, -OCX's, -OCHX'2;-OCH2X1, -0CH3, -OCH2R1A, -N3, -CN, -SOn1R1D, SOv1NR1AR1B, -NHC(O)NR1AR1B, -N(O)mi, -NR1AR1B, -C(O)R1C, -C(O)-OR1C, -C(O)NR1AR1B, -OR1D, -NR1ASO2R1D, -NR1AC(O)R1C, -NR1AC( O)OR1C, -NR1AOR1C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R2is independently absent, hydrogen, halogen, -CX23, -CHX2, -CH2X, -OCX3, -OCHX2, -OCH2X2, -OCH3, -OCH2R2A, -N3, -CN, -S0n2R1D, SOv2NR2AR2B, -NHC(O)NR2AR2B, -N(O)m2, -NR2AR2B, -C(O)R2C, -C(O)-OR2C, -C(O)NR2AR2B, -OR2D, -NR2ASO2R2D, -NR2AC(O)R2C, -NR2AC( O)OR2C, -NR2AOR2C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R3is independently absent, hydrogen, halogen, -CX33, -CHX32, -CH2X3, -OCX33, -OCHX32, -OCH2X3, -0CH3, -OCH2R3A, -N3, -CN, -SOn3R3D, SOv3NR3AR3B, -NHC(O)NR3AR3B, -N(O)m3, -NR3AR3B, -C(O)R3C, -C(O)-OR3C, -C(O)NR3AR3B, -OR3D, -NR3ASO2R3D, -NR3AC(O)R3C, -NR3AC( O)OR3C, -NR3AOR3C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R4is independently hydrogen, halogen, -CX43, -CHX42, -CH2X4, -OCX43, -OCHX42. -OCH2X4, -0CH3, -OCH2R4A, -N3, -CN, -SOn4R4D, SOv4NR4AR4B, -NHC(O)NR4AR4B, -N(O)m4, -NR4AR4B, -C(O)R4C, -C(O)-OR4C, -C(O)NR4AR4B, -OR4D, -NR4ASO2R4D, -NR4AC(O)R4C, -NR4AC( O)OR4C, -NR4AOR4C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R5is independently hydrogen, halogen, -CX53, -CHX52, -CH2X5, -OCX’s, -OCHX52, -OCH2X5, -0CH3, -OCH2R5A, -N₃, -CN, -SOn5R5D, SOv5NR5AR5B, -NHC(O)NR5AR5B, -N(O)m5, -NR5AR5B, -C(O)R5C, -C(O)-OR5C, -C(O)NR5AR5B, -OR5D, -NR5ASO2R5D, -NR5AC(O)R5C, -NR5AC( O)OR5C, -NR5AOR5C, substituted orunsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R6is independently hydrogen, halogen, -CX63, -CHX62, -CH2X6, -OCX63, -OCHX62, -OCH2X6, -0CH3, -OCH2R6A, -N3, -CN, -SOn6R6D, SOV6NR6AR6B, -NHC(O)NR6AR6B, -N(O)m6, -NR6AR6B, -C(O)R6C, -C(O)-OR6C, -C(O)NR6AR6B, -OR6D, -NR6ASO2R6D, -NR6AC(O)R6C, -NR6AC( O)OR6C, -NR6AOR6C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R7is independently hydrogen, halogen, -CX73, -CHX72, -CH2X7, -OCX73, -OCHX72. -OCH2X7, -0CH3, -OCH2R7A, -N3, -CN, -SOn7R7D, SOv7NR7AR7B, -NHC(O)NR7AR7B, -N(O)m7, -NR7AR7B, -C(O)R7C, -C(O)-OR7C, -C(O)NR7AR7B, -OR7D, -NR7ASO2R7D, -NR7AC(O)R7C, -NR7AC( O)OR7C, -NR7AOR7C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R8is independently hydrogen, halogen, -CX83, -CHX82, -CH2X8, -OCX83, -OCHX82, -OCH2X8, -0CH3, -OCH2R8A, -N3, -CN, -SOn8R8D, SOv8NR8AR8B, -NHC(O)NR8AR8B, -N(O)m8, -NR8AR8B, -C(O)R8C, -C(O)-OR8C, -C(O)NR8AR8B, -OR8D, -NR8ASO2R8D, -NR8AC(O)R8C, -NR8AC( O)OR8C, -NR8AOR8C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R9is independently absent, hydrogen, halogen, -CX93, -CHX92, -CH2X9, -OCX93, -OCHX92, -OCH2X9, -0CH3, -OCH2R9A, -N3, -CN, -SOn9R9D, SOV9NR9AR9B, -NHC(O)NR9AR9B, -N(O)m9, -NR9AR9B, -C(O)R9C, -C(O)-OR9C, -C(O)NR9AR9B, -OR9D, -NR9ASO2R9D, -NR9AC(O)R9C, -NR9AC( O)OR9C, -NR9AOR9C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R10is independently absent, hydrogen, halogen, -CX103, -CHX102, - CH2X10, -OCX103, -OCHX102,-OCH2X10, -0CH3, -OCH2R10A, -N3, -CN, -SOn10R10D, SOv10NR10AR10B, -NHC(O)NR10AR10B, -N(O)m10, -NR10AR10B, -C(O)R10C, -C(O)-OR10C, - C(O)NR10AR10B, -OR10D, -NR10ASO2R10D, -NR10AC(O)R10C, -NR10AC(O)OR10C, - NR10AOR10C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R12is substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;wherein R1A, R1B, R1C, R1D, R2A, R2B, R2C, R2D, R3A, R3B, R3C, R3D, R4A, R4B, R4C, R4D, R5A, R5B, R5C, R5D, R6A, R6B, R6C, R6D, R7A, R7B, R7C, R7D, R8A, R8B, R8C,R8D, R9A, R9B, R9C, R9D, R10A, R10B, R10C, R1OD, R11and R12are independently hydrogen, halogen, -CX3, -CHX2, -CH2X, -COOH, -CONH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;Y1is independently -C(R1)=, -C(L1A)=, or -N=;Y2is independently -C(R2)=, -C(L1A)=, or -N=;Y3is independently -C(R3)=, -C(L1A)=, or -N=;Y9is independently -C(R9)=, -C(L1A)=, or -N=;Y10is independently -C(R10)=, -C(L1A)=, or -N=;L1Ais a bond;n1, n2, n3, n4, n5, n6, n7, n8, n9, n10 and n11 are independently an integer from 0 to 4; m1, m2, m3, m4, m5, m6, m7, m8, m9, m10, vl, v2, v3, v4, v5, v6, v7, v8, v9, vlO, and vll are independently an integer from 1 to 2; andX, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10are independently-F, -Cl, -Br, or-I.

3. The method of claim 2, wherein the small molecule inhibitor is:

4. The method of claim 2, wherein the small molecule inhibitor is a pharmaceutically acceptable salt and / or prodrug thereof.

5. The method of claim 1, wherein the small molecule inhibitor is a compound represented by Formula (II):wherein:L1is a bond to L1A, -SOniiL1A-, -SOv11NR11L1A-, -NHC(O)NR11L1A-, -NR11L1A-, -C(O)L1A-, -C(O)OL1A-, -C(O)NR11L1A-, -OL1A-, -NR11SO2L1A-, NR11C(O)L1A-, -NR11C(O)OL1A-, NR11OL1A-SL1A-, -substituted alkyl-L1A-, -unsubstituted alkyl-L1A-, -substituted heteroalkyl-L1A-, -unsubstituted heteroalkyl-L1A-, -substituted alkylene-L1A-, -unsubstituted alkylene-L1A-, -substituted heteroalkylene-L1A-, -unsubstituted heteroalkylene-L1A-, -substituted cycloalkylene-L1A-, -unsubstituted cycloalkylene-L1A-, -substitutedheterocycloalkylene-L1A-, -unsubstituted heterocycloalkylene-L1A-, -unsubstituted arylene-L1A-, -unsubstituted arylene-L1A-, -substituted heteroarylene-L1A-, or -unsubstituted heteroarylene-L1A-R1is independently hydrogen, halogen, -CX13, -CHX12, -CH2X1, -OCX13, -OCHX12-OCH2X1, -OCH3, -OCH2R1A, -N3, -CN, -SOn1R1D, SOv1NR1AR1B, - NHC(O)NR1AR1B, -N(O)mi, -NR1AR1B, -C(O)R1C, -C(O)-OR1C, -C(O)NR1AR1B, -OR1D, - NR1ASO2R1D, -NR1AC(O)R1C, -NR1AC( O)OR1C, -NR1AOR1C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R2is independently hydrogen, halogen, -CX23, -CHX2, -CH2X, -OCX23, -OCHX22. -OCH2X2, -OCH3, -OCH2R2A, -N3, -CN, -SOn2R1D, SOv2NR2AR2B, - NHC(O)NR2AR2B, -N(O)m2, -NR2AR2B, -C(O)R2C, -C(O)-OR2C, -C(O)NR2AR2B, -OR2D, - NR2ASO2R2D, -NR2AC(O)R2C, -NR2AC( O)OR2C, -NR2AOR2C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R3is independently hydrogen, halogen, -CX33, -CHX32, -CH2X3, -OCX33, -OCHX32, -OCH2X3, -0CH3, -OCH2R3A, -N3, -CN, -SOn3R3D, SOv3NR3AR3B, - NHC(O)NR3AR3B, -N(O)m3, -NR3AR3B, -C(O)R3C, -C(O)-OR3C, -C(O)NR3AR3B, -OR3D, - NR3ASO2R3D, -NR3AC(O)R3C, -NR3AC( O)OR3C, -NR3AOR3C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R4is independently hydrogen, halogen, -CX43, -CHX42, -CH2X4, -OCX43, -OCHX42. -OCH2X4, -0CH3, -OCH2R4A, -N3, -CN, -SOn4R4D, SOv4NR4AR4B, - NHC(O)NR4AR4B, -N(O)m4, -NR4AR4B, -C(O)R4C, -C(O)-OR4C, -C(O)NR4AR4B, -OR4D, - NR4ASO2R4D, -NR4AC(O)R4C, -NR4AC( O)OR4C, -NR4AOR4C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R5is independently hydrogen, halogen, -CX53, -CHX52, -CH2X5, -OCX53, -OCHX52. -OCH2X5, -0CH3, -OCH2R5A, -N3, -CN, -SOn5R5D, SOv5NR5AR5B, -NHC(O)NR5AR5B, -N(O)m5, -NR5AR5B, -C(O)R5C, -C(O)-OR5C, -C(O)NR5AR5B, -OR5D, -NR5ASO2R5D, -NR5AC(O)R5C, -NR5AC( O)OR5C, -NR5AOR5C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R6is independently absent, hydrogen, halogen, -CX63, -CHX62, -CH2X6, -OCX63, -OCHX62, -OCH2X6, -0CH3, -OCH2R6A, -N3, -CN, -SOn6R6D, SOV6NR6AR6B, -NHC(O)NR6AR6B, -N(O)m6, -NR6AR6B, -C(O)R6C, -C(O)-OR6C, -C(O)NR6AR6B, -OR6D, -NR6ASO2R6D, -NR6AC(O)R6C, -NR6AC( O)OR6C, -NR6AOR6C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R7is independently absent, hydrogen, halogen, -CX73, -CHX72, -CH2X7, -OCX73, -OCHX72, -OCH2X7, -0CH3, -OCH2R7A, -N3, -CN, -SOn7R7D, SOv7NR7AR7B, -NHC(O)NR7AR7B, -N(O)m7, -NR7AR7B, -C(O)R7C, -C(O)-OR7C, -C(O)NR7AR7B, -OR7D, -NR7ASO2R7D, -NR7AC(O)R7C, -NR7AC( O)OR7C, -NR7AOR7C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R8is independently absent, hydrogen, halogen, -CX83, -CHX82, -CH2X8, -OCX83, -OCHX82, -OCH2X8, -0CH3, -OCH2R8A, -N3, -CN, -SOn8R8D, SOv8NR8AR8B, -NHC(O)NR8AR8B, -N(O)m8, -NR8AR8B, -C(O)R8C, -C(O)-OR8C, -C(O)NR8AR8B, -OR8D, -NR8ASO2R8D, -NR8AC(O)R8C, -NR8AC( O)OR8C, -NR8AOR8C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R9is independently absent, hydrogen, halogen, -CX93, -CHX92, -CH2X9, -OCX93, -OCHX92, -OCH2X9, -0CH3, -OCH2R9A, -N3, -CN, -SOn9R9D, SOV9NR9AR9B, -NHC(O)NR9AR9B, -N(O)m9, -NR9AR9B, -C(O)R9C, -C(O)-OR9C, -C(O)NR9AR9B, -OR9D, -NR9ASO2R9D, -NR9AC(O)R9C, -NR9AC( O)OR9C, -NR9AOR9C, substituted orunsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R10is independently absent, hydrogen, halogen, -CX103, -CHX102, -CH2X10, -OCX103, -OCHX102,-OCH2X10, -0CH3, -OCH2R10A, -N3, -CN, -SOn10R10D, SOv10NR10AR10B, -NHC(O)NR10AR10B, -N(O)m10, -NR10AR10B, -C(O)R10C, -C(O)-OR10C, -C(O)NR10AR10B, -OR10D, -NR10ASO2R10D, -NR10AC(O)R10C, -NR10AC(O)OR10C, -NR10AOR10C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R12is independently absent, hydrogen, halogen, -CX123, -CHX122, -CH2X12, -OCX123, -OCHX122,-OCH2X12, -0CH3, -OCH2R12A, -N3, -CN, -SOn12R12D, SOv12NR12AR12B, -NHC(O)NR12AR12B, -N(O)m12, -NR12AR12B, -C(O)R12C, -C(O)-OR12C, -C(O)NR12AR12B, -OR12D, -NR12ASO2R12D, -NR12AC(O)R12C, -NR12AC( O)OR12C, -NR12AOR12C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;wherein R1A, R1B, R1C, R1D, R2A, R2B, R2C, R2D, R3A, R3B, R3C, R3D, R4A, R4B, R4C, R4D, R5A, R5B, R5C, R5D, R6A, R6B, R6C, R6D, R7A, R7B, R7C, R7D, R8A, R8B, R8CR8D, R9A, R9B, R9C, R9D, R1OA, R1OBR1OC, R1OD, R11and R12A, R12B, R12C, R12Dare independently hydrogen, -CX3, -CHX2, -CH2X, -COOH, -CONH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;Y6is independently -C(R6)=, -C(L1A)=, -C(R6)H-, -C(L1A)H-, -(R6)C(L1A)-, -(OH)C(R6)-, -(OH)C(L1A)-, -O-, -S-, -N=, -N(R6)-, -N(L1A)-, -SO2-;Y7is independently -C(R7)=,-C(L1A)=, -C(R7)H-, -C(L1A)H-, -(R7)C(L1A)-, -(OH)C(R7)-, -(OH)C(L1A)-, -O-, -S-, -N=, -N(R7)-, -N(L1A)-, -SO2-;Y8is independently -C(R8)=,-C(L1A)=, -C(R8)H-, -C(L1A)H-, -(R8)C(L1A)-, -(OH)C(R8)-, -(OH)C(L1A)-, -O-, -S-, -N=, -N(R8)-, -N(L1A)-, -SO2-;Y9is independently -C(R9)=,-C(L1A)=, -C(R9)H-, -C(L1A)H-, -(R9)C(L1A)-, -(OH)C(R9)-, -(OH)C(L1A)-, -O-, -S-, -N=, -N(R9)-, -N(L1A)-, -SO2-;Y10is independently -C(R10)=,-C(L1A)=, -C(R10)H-, -C(L1A)H-, - (R10)C(L1A)-, -(OH)C(L1A)-, -(OH)C(L1A)-, -O-, -S-, -N=, -N(R10)-, -N(L1A)-, -SO2-;Y12is independently -C(R12)=,-C(L1A)=, -C(R12)H-, -C(L1A)H-, - (R12)C(L1A)-, -(OH)C(R12)-, -(OH)C(L1A)-, -O-, -S-, -N=, -N(R12)-, -N(L1A)-, -SO2-;L1Ais a bond;n1, n2, n3, n4, n5, n6, n7, n8, n9, n10, n11 and n12 are independently an integer from 0 to 4; m1, m2, m3, m4, m5, m6, m7, m8, m9, m10, m12, v1, v2, v3, v4, v5, v6, v7, v8, v9, v10, v11, and v12 are independently an integer from 1 to 2; andX, X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, and X12are independently-F, - Cl, -Br, or-I.

6. The method of claim 5, wherein the small molecule inhibitor is:

7. The method of claim 5, wherein the small molecule inhibitor is a pharmaceutically acceptable salt and / or prodrug thereof.

8. The method of claim 1, wherein the small molecule inhibitor is a compound represented by Formula (III):R6R5(III), wherein:L1is a bond, -SOn11L1A-, -SOv11NR11L1A-, -NHC(O)NR11L1A-, -NR11L1A-, -C(O)L1A-, -C(O)OL1A-, -C(O)NRnL1A-, -OL1A-, -NR11SO2L1A-, NR11C(O)L1A-, -NR11C(O)OL1A-, NR11OL1A, -SL1A-, -substituted alkyl-L1A-, -unsubstituted alkyl-L1A-, -substituted heteroalkyl-L1A-, -unsubstituted heteroalkyl-L1A-, -substituted alkylene-L1A-, -unsubstituted alkylene-L1A-, -substituted heteroalkylene-L1A-, -unsubstituted heteroalkylene-L1A-, -substituted cycloalkylene-L1A-, -unsubstituted cycloalkylene-L1 A-, -substituted heterocycloalkylene-L1A-, -unsubstituted heterocycloalkylene-L1A-, -unsubstituted arylene-L1A-, -unsubstituted arylene-L1A-, -substituted heteroarylene-L1A-, or -unsubstituted heteroarylene-L1A-;L2is a bond, -SOni2L2A-, -SOvi2NR12L2A-, -NHC(O)NR12L2A-, -NR12L2A-, -C(O)L2A-, -C(O)OL2A-, -C(O)NR12L2A-, -OL2A-, -NR12SO2L2A-, NR12C(O)L2A-, -NR12C(O)OL2A-, NR12OL2A, -SL2A-, -substituted alkyl-L1A-, -unsubstituted alkyl-L1A-, -substituted heteroalkyl-L1A-, -unsubstituted heteroalkyl-L1A-, -substituted alkylene-L1A-, -unsubstituted alkylene-L1A-, -substituted heteroalkylene-L1A-, -unsubstituted heteroalkylene-L1A-, -substituted cycloalkylene-L1A-, -unsubstituted cycloalkylene-L1A-, -substituted heterocycloalkylene-L1A-, -unsubstituted heterocycloalkylene-L1A-, -unsubstituted arylene-L1A-, -unsubstituted arylene-L1 A-, -substituted heteroarylene-L1A-, or -unsubstituted heteroaryl ene-L1A-;R1is independently hydrogen, halogen,-CX13, -CHX12, -CH2X1, -OCX13, -OCHX12-OCH2X1, -OCH3, -OCH2R1A, -N3, -CN, -SOn1R1D, SOv1NR1AR1B, -NHC(O)NR1AR1B, -N(O)mi, -NR1AR1B, -C(O)R1C, -C(O)-OR1C, -C(O)NR1AR1B, -OR1D, -NR1ASO2R1D, -NR1AC(O)R1C, -NR1AC( O)OR1C, -NR1AOR1C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstitutedcycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R2is independently hydrogen, halogen, -CX23, -CHX2, -CH2X, -OCX3, -OCHX22. -OCH2X, -OCH3, -OCH2R2A, -N3, -CN, -SOn2R1D, SOv2NR2AR2B, -NHC(O)NR2AR2B, -N(O)m2, -NR2AR2B, -C(O)R2C, -C(O)-OR2C, -C(O)NR2AR2B, -OR2D, -NR2ASO2R2D, -NR2AC(O)R2C, -NR2AC( O)OR2C, -NR2AOR2C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R3is independently hydrogen, halogen, -CX33, -CHX32, -CH2X3, -OCX33, -OCHX32, -OCH2X3, -0CH3, -OCH2R3A, -N3, -CN, -SOn3R3D, SOv3NR3AR3B, -NHC(O)NR3AR3B, -N(O)m3, -NR3AR3B, -C(O)R3C, -C(O)-OR3C, -C(O)NR3AR3B, -OR3D, -NR3ASO2R3D, -NR3AC(O)R3C, -NR3AC( O)OR3C, -NR3AOR3C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R4is independently hydrogen, halogen, -CX43, -CHX42, -CH2X4, -OCX43, -OCHX42. -OCH2X4, -0CH3, -OCH2R4A, -N3, -CN, -SOn4R4D, SOv4NR4AR4B, -NHC(O)NR4AR4B, -N(O)m4, -NR4AR4B, -C(O)R4C, -C(O)-OR4C, -C(O)NR4AR4B, -OR4D, -NR4ASO2R4D, -NR4AC(O)R4C, -NR4AC( O)OR4C, -NR4AOR4C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R5is independently hydrogen, halogen, -CX53, -CHX52, -CH2X5, -OCX53, -OCHX52, -OCH2X5, -OCH3, -OCH2R5A, -N3, -CN, -SOn5R5D, SOv5NR5AR5B, -NHC(O)NR5AR5B, -N(O)m5, -NR5AR5B, -C(O)R5C, -C(O)-OR5C, -C(O)NR5AR5B, -OR5D, -NR5ASO2R5D, -NR5AC(O)R5C, -NR5AC( O)OR5C, -NR5AOR5C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R6is independently hydrogen, halogen, -CX63, -CHX62, -CH2X6, -OCX63, -OCHX62. -OCH2X6, -N3, -OCH3, -OCH2R6A, -CN, -SOn6R6D, SOv6NR6AR6B, -NHC(O)NR6AR6B, -N(O)m6, -NR6AR6B, -C(O)R6C, -C(O)-OR6C, -C(O)NR6AR6B, -OR6D, -NR6ASO2R6D, -NR6AC(O)R6C, -NR6AC(O)OR6C, -NR6AOR6C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R7is independently hydrogen, halogen, -CX73, -CHX72, -CH2X7, -OCX73, -OCHX72. -OCH2X7, -0CH3, -OCH2R7A, -N3, -CN, -SOn7R7D, SOv7NR7AR7B, -NHC(O)NR7AR7B, -N(O)m7, -NR7AR7B, -C(O)R7C, -C(O)-OR7C, -C(O)NR7AR7B, -OR7D, -NR7ASO2R7D, -NR7AC(O)R7C, -NR7AC( O)OR7C, -NR7AOR7C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;R8is independently hydrogen, halogen, -CX83, -CHX82, -CH2X8, -OCX83, -OCHX82, -OCH2X8, -0CH3, -OCH2R8A, -N3, -CN, -SOn8R8D, SOv8NR8AR8B, -NHC(O)NR8AR8B, -N(O)m8, -NR8AR8B, -C(O)R8C, -C(O)-OR8C, -C(O)NR8AR8B, -OR8D, -NR8ASO2R8D, -NR8AC(O)R8C, -NR8AC( O)OR8C, -NR8AOR8C, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;wherein R1A, R1B, R1C, R1D, R2A, R2B, R2C, R2D, R3A, R3B, R3C, R3D, R4A, R4B J^4C R4D J^5A J^5B J^5C R5D J^6A R6B R6C R6D RyA J^7B J^7C R7D R8A J^8BR8D, R11and R12are independently hydrogen, -CX3, -CHX2, -CH2X, -COOH, -CONH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted orunsubstituted heteroaryl;L1Ais a bond, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;L2Ais a bond, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkylene, substituted orunsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;n1, n2, n3, n4, n5, n6, n7, n8, n11 and n12 are independently an integer from 0 to 4; m1, m2, m3, m4, m5, m6, m7, m8, vl, v2, v3, v4, v5, v6, v7, v8, vll, and v12 are independently an integer from 1 to 2; andX, X1, X2, X3, X4, X5, X6, X7, and X8are independently-F, -Cl, -Br, or-I.

9. The method of claim 8, wherein the small molecule inhibitor is:

10. The method of claim 8, wherein the small molecule inhibitor is a pharmaceutically acceptable salt and / or prodrug thereof.

11. The method of claim 1, wherein the disorder is a cancer, wherein the cancer is selected from the group consisting of Cardiac: sarcoma (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyoma, fibroma, lipoma and teratoma; Lung: bronchogenic carcinoma (squamous cell, undifferentiated small cell, undifferentiated large cell, adenocarcinoma), alveolar (bronchiolar) carcinoma, bronchial adenoma, sarcoma, lymphoma, chondromatous hamartoma, mesothelioma; Gastrointestinal: esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumors, vipoma), small bowel (adenocarcinoma, lymphoma, carcinoid tumors, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large bowel (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma); Genitourinary tract: kidney (adenocarcinoma, Wilm's tumor (nephroblastoma), lymphoma, leukemia), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (adenocarcinoma, sarcoma), testis (seminoma, teratoma, embryonal carcinoma, teratocarcinoma,choriocarcinoma, sarcoma, interstitial cell carcinoma, fibroma, fibroadenoma, adenomatoid tumors, lipoma); Liver: hepatoma (hepatocellular carcinoma), cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; Biliary tract: gall bladder carcinoma, ampullary carcinoma, cholangiocarcinoma; Bone: osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochronfroma (osteocartilaginous exostoses), benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma and giant cell tumors; Nervous system: skull (osteoma, hemangioma, granuloma, xanthoma, osteitis deformans), meninges (meningioma, meningiosarcoma, gliomatosis), brain (astrocytoma, medulloblastoma, glioma, ependymoma, germinoma (pinealoma), glioblastoma multiform, oligodendroglioma, schwannoma, retinoblastoma, congenital tumors), spinal cord neurofibroma, meningioma, glioma, sarcoma); Gynecological: uterus (endometrial'carcinoma (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa-thecal cell tumors, Sertoli-Leydig cell tumors, dysgerminoma, malignant teratoma), vulva (squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma), vagina (clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonal rhabdomyosarcoma), fallopian tubes (carcinoma); Hematologic: blood (myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative diseases, multiple myeloma, myelodysplastic syndrome), Hodgkin's disease, non-Hodgkin's lymphoma (malignant lymphoma); Skin: malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, moles dysplastic nevi, lipoma, angioma, dermatofibroma, keloids, psoriasis; Adrenal glands: neuroblastoma; and combinations thereof.

12. The method of claim 1, wherein the disorder is a neurological disorder selected from epilepsy, parkinson’s disease, schizophrenia, acquired neuromyotonia, episodic ataxia type 1, hereditary deafness syndromes, atrial fibrillation, multiple sclerosis, musculoskeletal disorders, bipolar disorder, sudden unexpected death in epilepsy (SUDEP), and combinations thereof.

13. The method of claim 1, wherein the disorder is a genetic disorder selected from epilepsy, cardiac arrhythmias, periodic muscle paralysis, episodic ataxia type 1, syndromicdevelopmental disorders: zimmermann-laband syndrome, temple-baraister syndrome, FHEIG syndrome; and combinations thereof.

14. The method of anf of claims 1-13, wherein the therapeutically effective amount of the compound is between about 0.01 to 5.0 mg / kg per day.

15. A pharmaceutical composition, comprising a therapeutically effective amount of a compound of any of claims 1-10, and a pharmaceutically acceptable carrier, excipient and / or diluents.

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