Reversible lysine covalent modifiers of CDK2 and uses thereof

Abstract

In some aspects, the present disclosure provides compounds of Formula (I), (II), (ll-A), (ll-B), (ll-C), (ll-D), (ll-E), (ll-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), or pharmaceutically acceptable salts thereof, for the modulation of CDK2. In another aspect, the present disclosure provides methods for the treatment of diseases or disorders mediated by CDK2, such as oncology indications, using compounds of Formula (I), (II), (ll-A), (ll-B), (ll-C), (ll-D), (ll-E), (ll-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), or pharmaceutically acceptable salts thereof.

Description

REVERSIBLE LYSINE COVALENT MODIFIERS OF CDK2 AND USES THEREOF CROSS REFERENCE

[0001] This application claims the benefit of U.S. Provisional Application No.63 / 545,413 filed on October 24, 2023, and U.S. Provisional Application No.63 / 674,639 filed on July 23, 2024, the entirety of each is incorporated herein by reference. BACKGROUND OF THE INVENTION

[0002] Cyclin-Dependent Kinases (CDK) are a family of serine / threonine kinases involved in cell-cycle progression and cell division. The deregulation of CDK activity is associated with abnormal regulation of the cell cycle and is detected nearly all forms of human cancers (Sherr, C.J. Science, 1996, 274(5293), 1672-1677). Activation of CDK’s requires the heterodimerzation with other regulatory subunits, these dimers known as cyclins. One of these, Cyclin E (a CDK2 regulator) is frequently overexpressed in cancer. Its amplification or overexpression has long been associated with poor outcomes in breast cancer, inflammatory breast cancer, and trastuzmab resistance in HER2+ breast cancers (Keyomarsi, K. et al., N Engl J Med., 2002, 347, 1566-1575; Scaltriti, M. et al., Proc Natl Acad Sci.2011, 108, 3761-3766; Alexander, A. et al., Oncotarget 2017, 8, 14897-14911). Additionally, cyclin E1 amplification or overexpression is associated with poor outcomes in ovarian, gastric, endometrial and other cancers (Nakayama, N. et al., Cancer 2010, 116, 2621-2634; Etemadmoghadam, D. et al., Clin Cancer Res 2013, 19, 5960-5971). However, developing CDK2 selective inhibitors has been difficult due to its similarity to other CDK’s. To date there have been no approved agents selectively targeting CDK2. Accordingly, there is need to develop new selective CDK2 modulators for oncology. SUMMARY OF THE INVENTION

[0003] In one aspect, the present disclosure provides a compound represented by the structure of Formula (I)or a pharmaceutically acceptable salt thereof wherein: Ring A is selected from C3-12carbocycle and 3- to 12-membered heterocycle; R5is selected from an electrophilic moiety or a prodrug thereof;each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, - S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, - SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; L is represented by -L1- L2-L3-L4-, wherein L1, L2, L3, and L4are each independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, - (R12)NC(O)N(R12)-, and–-(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN; wherein L2, L3, and L4are each optionally absent; wherein no more than two of L1, L2, L3, and L4are selected from (a) and the two selected are not adjacent; R1and R2are each independently selected from (i), (ii), and (iii): (i) hydrogen, -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -C(O)OR14, -OC(O)R14, - N(R14)C(O)OR14, N(R14)C(O)R14, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, and -CN; (ii) C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from:halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), - CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; or R1and R2may come together to form a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, - C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, -N(R15)C(O)N(R15)2, - S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15,-C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, -N(R15)C(O)N(R15)2, - S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN; R3is selected from: hydrogen, halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -C(O)OR16, -NO2, - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -C(O)OR16, - NO2, and -CN; R11, R12, R13, R14, R15, and R16are each independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted with one more substituents independently selected from halogen, -O- C1-6alkyl, -O-C1-6haloalkyl, -NH2, -NO2, =O, -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein each C3-10carbocycle and 3- to 10-membered heterocycle are optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2, -NO2, =O, and -CN; and C3-6carbocycle and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2, -NO2, =O, and -CN; n is selected from 0, 1, 2, 3, and 4; and m is selected from 0 and 1.

[0004] In some embodiments, the electrophilic moiety or a prodrug thereof is a lysine reactive electrophile. In some embodiments, the lysine reactive electrophile is selected from a reversible lysine reactive electrophile and an irreversible lysine reactive electrophile. In some embodiments, wherein the electrophilic moiety is selected from a haloacetamide, a haloalkyl ketone, a halo amidine, a halo benzylphosphonate, an acyloxyalkyl ketone, a sulfonyl oxirane, an epoxide, a diazoalkyl ketone, a halotriazine, an acrylamide, a cyano acrylamide, a vinyl sulfone, a vinyl sulfonamide, an acrylate, an aldehyde, a borate, a halosulfonyl, an ester, squaric ester, squaramide ester, a fumarate, a carbonyl acrylate, a maleimide, a ketoamide, a nitrile, an alkene, an alkyne, a keto heterocycle, and an ynamide. In some embodiments, the electrophilic moiety or prodrug thereof is an aldehyde or a prodrug thereof. In some embodiments, the electrophilic moiety or prodrug thereof is an imine. In some embodiments, the electrophilic moiety or prodrug thereof is an aldehyde.

[0005] In another aspect, a compound or salt of Formula (I) is represented by the structure of Formula (II):pharmaceutically acceptable salt thereof.

[0006] In another aspect, a compound or salt of Formula (I) is represented by the structure of Formula (III):pharmaceutically acceptable salt thereof.

[0007] In one aspect, the present disclosure provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula (I), (II), (II-A), (II-B), (II- C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), or a pharmaceutically acceptable salt thereof.

[0008] In another aspect, the present disclosure provides a method of modulating CDK2 comprising administering to a subject in need thereof a compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), or a pharmaceutical composition thereof.

[0009] In another aspect, the present disclosure provides a method of inhibiting CDK2 comprising administering to a subject in need thereof a compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), or a pharmaceutical composition thereof.

[0010] In another aspect, the present disclosure provides a method of treating a disease or disorder mediated by CDK2 comprising administering to a subject in need thereof a compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), or a pharmaceutical composition thereof.

[0011] In another aspect, the present disclosure provides a method of treating cancer comprising administering to a subject in need thereof a compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), or a pharmaceutical composition thereof.

[0012] In another aspect, the present disclosure provides a method of inhibiting cell proliferation comprising administering to a subject in need thereof a compound or salt of Formula (I), (II),(II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), or a pharmaceutical composition thereof. INCORPORATION BY REFERENCE

[0013] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The novel features of the invention are set forth with particularity in the instant claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:

[0015] FIGS.1A-1P provide intact-protein mass spectra for pCDK2-CCNE1 incubated with compound of the present disclosure both without a competitor molecule and with a significant stoichiometric excess of a competitor molecule (PF-06873600). FIGS.1A-1B provide intact- protein mass spectra for pCDK2-CCNE1 incubated with Compound 11, both without a competitor and with a significant stoichiometric excess of a competitor molecule PF-06873600, respectively. FIGS.1C-1D provide intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 13, both without a competitor and with a significant stoichiometric excess of a competitor molecule PF-06873600, respectively. FIGS.1E-1F provide intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 17, both without a competitor and with a significant stoichiometric excess of a competitor molecule PF-06873600, respectively. FIGS. 1G-1H provide intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 17, both without a competitor and with a significant stoichiometric excess of a competitor molecule PF-06873600, respectively. FIGS.1I-1J provide intact-protein mass spectra for pCDK2- CCNE1 incubated with Compound 22, both without a competitor and with a significant stoichiometric excess of a competitor molecule PF-06873600, respectively. FIGS.1K-1L provide intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 51, both without a competitor and with a significant stoichiometric excess of a competitor molecule PF- 06873600, respectively. FIGS.1M-1N provide intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 69, both without a competitor and with a significant stoichiometric excess of a competitor molecule PF-06873600, respectively. FIGS.1O-1P provide intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 32, both without a competitor and with a significant stoichiometric excess of a competitor molecule PF-06873600, respectively.

[0016] FIGS 2A-2N provide intact-protein mass spectra for pCDK2-CCNE1 proteins after incubation with compounds of the present disclosure and subsequent sodium borohydride reduction. FIG.2A provides intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 11. FIG.2B provides intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 13. FIG.2C provides intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 17. FIG.2D provides intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 22. FIG.2E provides intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 16. FIG.2F provides intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 51. FIG.2G provides intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 64. FIG.2H provides intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 69. FIG.2I provides intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 45. FIG.2J provides intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 32. FIG.2K provides intact-protein mass spectra for pCDK2- CCNE1 incubated with Compound 49. FIG.2L provides intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 82. FIG.2M provides intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 89. FIG.2N provides intact-protein mass spectra for pCDK2-CCNE1 incubated with Compound 103.

[0017] FIGS.3A-3N provide dissociation rate data for pCDK2-CCNE1 treated with compounds of the present disclosure via competition with excess PF-06873600. FIG 3A illustrates off-rate studies of Compound 11 with pCDK2-CCNE1. FIG 3B illustrates off-rate studies of Compound 13 with pCDK2-CCNE1. FIG 3C illustrates off-rate studies of Compound 17 with pCDK2- CCNE1. FIG 3D illustrates off-rate studies of Compound 22 with pCDK2-CCNE1. FIG 3E illustrates off-rate studies of Compound 16 with pCDK2-CCNE1. FIG 3F illustrates off-rate studies of Compound 51 with pCDK2-CCNE1. FIG 3G illustrates off-rate studies of Compound 64 with pCDK2-CCNE1. FIG 3H illustrates off-rate studies of Compound 69 with pCDK2- CCNE1. FIG 3I illustrates off-rate studies of Compound 45 with pCDK2-CCNE1. FIG 3J illustrates off-rate studies of Compound 32 with pCDK2-CCNE1. FIG 3K illustrates off-rate studies of Compound 49 with pCDK2-CCNE1. FIG 3L illustrates off-rate studies of Compound 82 with pCDK2-CCNE1. FIG 3M illustrates off-rate studies of Compound 89 with pCDK2- CCNE1. FIG 3N illustrates off-rate studies of Compound 103 with pCDK2-CCNE1.

[0018] FIGS.4A-4C provide diagrams of the co-crystal structure for the pCDK2-CCNE1 complex with Compound 13. FIG.4A provides a 2-D diagram from the co-crystal structure ofthe pCDK2-CCNE1 complex with Compound 13 with the pCDK2-CCNE1 rendered in cartoon model and Compound 13 with the CDK2 lysine residue K89 rendered in stick model. FIG.4B provides a 2-D diagram close-up from the co-crystal structure of the pCDK2-CCNE1 complex with Compound 13 depicted by a thicker stick model and the residues pCDK2-CCNE1 depicted by a thinner stick model. FIG.4C provides a 2-D diagram close-up from the co-crystal structure of the pCDK2-CCNE1 complex with Compound 13 detailing the interactions between the residues of CDK2 and Compound 13, specifically showing the imine bond between K89 lysine residue of CDK2 and Compound 13.

[0019] FIGS.5A-5C provide diagrams of the co-crystal structure for the pCDK2-CCNE1 complex with Compound 17. FIG.5A provides a 2-D diagram from the co-crystal structure of the pCDK2-CCNE1 complex with Compound 17 with the pCDK2-CCNE1 rendered in cartoon model and Compound 17 with the CDK2 lysine residue K89 rendered in stick model. FIG.5B provides a 2-D diagram close-up from the co-crystal structure of the pCDK2-CCNE1 complex with Compound 17 with Compound 17 depicted by a thicker stick model and the residues pCDK2-CCNE1 depicted by a thinner stick model. FIG.5C provides a 2-D diagram close-up from the co-crystal structure of the pCDK2-CCNE1 complex with Compound 17 detailing the interactions between the residues of CDK2 and Compound 17, specifically showing the imine bond between K89 lysine residue of CDK2 and Compound 17.

[0020] FIGS.6A-6C provide diagrams of the co-crystal structure for the pCDK2-CCNE1 complex with Compound 64. FIG.6A provides a 2-D diagram from the co-crystal structure of the pCDK2-CCNE1 complex with Compound 64 the pCDK2-CCNE1 rendered in cartoon model and Compound 64 with the CDK2 lysine residue K89 rendered in stick model. FIG.6B provides a 2-D diagram close-up from the co-crystal structure of the pCDK2-CCNE1 complex with Compound 64depicted by a thicker stick model and the residues pCDK2-CCNE1 depicted by a thinner stick model. FIG.6C provides a 2-D diagram close-up from the cocrystal structure of the pCDK2-CCNE1 complex with Compound 64detailing the interactions between the residues of CDK2 and Compound 64, specifically showing the imine bond between K89 lysine residue of CDK2 and Compound 64.

[0021] FIGS.7A-7B provide plasma concentrations for compounds 64 and 64a following oral and IV administration to mice. FIG.7A shows plasma concentrations for compounds 64 and 64a following oral administration to mice. FIG.7B shows plasma concentrations for compounds 64 and 64 following IV administration to mice.DETAILED DESCRIPTION OF THE INVENTION

[0022] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby. Definitions

[0023] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this invention belongs. All patents and publications referred to herein are incorporated by reference.

[0024] As used in the specification and claims, the singular form “a”, “an” and “the” includes plural references unless the context clearly dictates otherwise.

[0025] "Alkyl" refers to a straight or branched hydrocarbon chain monovalent radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, and preferably having from one to twelve carbon atoms (i.e., C1-C12alkyl). The alkyl is attached to the remainder of the molecule through a single bond. In certain embodiments, an alkyl comprises one to twelve carbon atoms (i.e., C1-C12 alkyl). In certain embodiments, an alkyl comprises one to eight carbon atoms (i.e., C1-C8alkyl). In other embodiments, an alkyl comprises one to five carbon atoms (i.e., C1-C5alkyl). In other embodiments, an alkyl comprises one to four carbon atoms (i.e., C1- C4 alkyl). In other embodiments, an alkyl comprises one to three carbon atoms (i.e., C1-C3 alkyl). In other embodiments, an alkyl comprises one to two carbon atoms (i.e., C1-C2alkyl). In other embodiments, an alkyl comprises one carbon atom (i.e., C1alkyl). In other embodiments, an alkyl comprises five to fifteen carbon atoms (i.e., C5-C15alkyl). In other embodiments, an alkyl comprises five to eight carbon atoms (i.e., C5-C8 alkyl). In other embodiments, an alkyl comprises two to five carbon atoms (i.e., C2-C5alkyl). In other embodiments, an alkyl comprises three to five carbon atoms (i.e., C3-C5alkyl). For example, the alkyl group may be attached to the rest of the molecule by a single bind, such as, methyl, ethyl, 1-propyl (n-propyl), 1- methylethyl (iso-propyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso- butyl), 1,1-dimethylethyl (tert-butyl), 1-pentyl (n-pentyl), and the like.

[0026] "Alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, andpreferably having from two to twelve carbon atoms (i.e., C2-C12 alkenyl). In certain embodiments, an alkenyl comprises two to eight carbon atoms (i.e., C2-C8alkenyl). In certain embodiments, an alkenyl comprises two to six carbon atoms (i.e., C2-C6alkenyl). In other embodiments, an alkenyl comprises two to four carbon atoms (i.e., C2-C4 alkenyl). The alkenyl is attached to the rest of the molecule by a single bond, for example, ethenyl (i.e., vinyl), prop-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the like.

[0027] "Alkynyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, and preferably having from two to twelve carbon atoms (i.e., C2-C12alkynyl). In certain embodiments, an alkynyl comprises two to eight carbon atoms (i.e., C2-C8alkynyl). In other embodiments, an alkynyl comprises two to six carbon atoms (i.e., C2-C6 alkynyl). In other embodiments, an alkynyl comprises two to four carbon atoms (i.e., C2-C4alkynyl). The alkynyl is attached to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.

[0028] "Alkylene" refers to a straight divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing no unsaturation, and preferably having from one to twelve carbon atoms, for example, methylene, ethylene, propylene, butylene, and the like. The alkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkylene chain to the rest of the molecule and to the radical group are through the terminal carbons respectively. Alkylene chain may be optionally substituted by one or more substituents such as those substituents described herein. In certain embodiments, an alkylene comprises one to ten carbon atoms (i.e., C1-C10alkylene). In certain embodiments, an alkylene comprises one to eight carbon atoms (i.e., C1-C8 alkylene). In other embodiments, an alkylene comprises one to five carbon atoms (i.e., C1-C5alkylene). In other embodiments, an alkylene comprises one to four carbon atoms (i.e., C1-C4alkylene). In other embodiments, an alkylene comprises one to three carbon atoms (i.e., C1-C3alkylene). In other embodiments, an alkylene comprises one to two carbon atoms (i.e., C1-C2alkylene). In other embodiments, an alkylene comprises one carbon atom (i.e., C1alkylene). In other embodiments, an alkylene comprises five to eight carbon atoms (i.e., C5-C8alkylene). In other embodiments, an alkylene comprises two to five carbon atoms (i.e., C2- C5alkylene). In other embodiments, an alkylene comprises three to five carbon atoms (i.e., C3-C5alkylene).

[0029] "Alkenylene" refers to a straight divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon double bond, and preferably having from two to twelve carbon atoms. Thealkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkenylene chain to the rest of the molecule and to the radical group are through the terminal carbons respectively. Alkenylene chain may be optionally substituted by one or more substituents such as those substituents described herein. In certain embodiments, an alkenylene comprises two to ten carbon atoms (i.e., C2-C10alkenylene). In certain embodiments, an alkenylene comprises two to eight carbon atoms (i.e., C2-C8 alkenylene). In other embodiments, an alkenylene comprises two to five carbon atoms (i.e., C2-C5 alkenylene). In other embodiments, an alkenylene comprises two to four carbon atoms (i.e., C2-C4alkenylene). In other embodiments, an alkenylene comprises two to three carbon atoms (i.e., C2-C3alkenylene). In other embodiments, an alkenylene comprises two carbon atom (i.e., C2alkenylene). In other embodiments, an alkenylene comprises five to eight carbon atoms (i.e., C5-C8alkenylene). In other embodiments, an alkenylene comprises three to five carbon atoms (i.e., C3-C5alkenylene).

[0030] "Alkynylene" refers to a straight divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon triple bond, and preferably having from two to twelve carbon atoms. The alkynylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkynylene chain to the rest of the molecule and to the radical group are through the terminal carbons respectively. Alkynylene chain may be optionally substituted by one or more substituents such as those substituents described herein. In certain embodiments, an alkynylene comprises two to ten carbon atoms (i.e., C2-C10alkynylene). In certain embodiments, an alkynylene comprises two to eight carbon atoms (i.e., C2-C8alkynylene). In other embodiments, an alkynylene comprises two to five carbon atoms (i.e., C2-C5 alkynylene). In other embodiments, an alkynylene comprises two to four carbon atoms (i.e., C2-C4 alkynylene). In other embodiments, an alkynylene comprises two to three carbon atoms (i.e., C2-C3alkynylene). In other embodiments, an alkynylene comprises two carbon atom (i.e., C2alkynylene). In other embodiments, an alkynylene comprises five to eight carbon atoms (i.e., C5-C8 alkynylene). In other embodiments, an alkynylene comprises three to five carbon atoms (i.e., C3-C5alkynylene).

[0031] The term “Cx-y” when used in conjunction with a chemical moiety, such as alkyl, alkenyl, or alkynyl is meant to include groups that contain from x to y carbons in the chain. For example, the term “C1-6alkyl” refers to substituted or unsubstituted saturated hydrocarbon groups, including straight-chain alkyl and branched-chain alkyl groups that contain from 1 to 6 carbons. The term -Cx-yalkylene- refers to a substituted or unsubstituted alkylene chain with from x to y carbons in the alkylene chain. For example, -C1-6alkylene- may be selected from methylene,ethylene, propylene, butylene, pentylene, and hexylene, any one of which is optionally substituted.

[0032] The terms “Cx-yalkenyl” and “Cx-yalkynyl” refer to unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond, respectively. The term -Cx-yalkenylene- refers to a substituted or unsubstituted alkenylene chain with from x to y carbons in the alkenylene chain. For example, - C2-6alkenylene- may be selected from ethenylene, propenylene, butenylene, pentenylene, and hexenylene, any one of which is optionally substituted. An alkenylene chain may have one double bond or more than one double bond in the alkenylene chain. The term -Cx-yalkynylene- refers to a substituted or unsubstituted alkynylene chain with from x to y carbons in the alkynylene chain. For example, -C2-6alkynylene- may be selected from ethynylene, propynylene, butynylene, pentynylene, and hexynylene, any one of which is optionally substituted. An alkynylene chain may have one triple bond or more than one triple bond in the alkynylene chain.

[0033] The term “carbocycle” as used herein refers to a saturated, unsaturated or aromatic ring in which each atom of the ring is carbon. Carbocycle include 3- to 10-membered monocyclic rings and 6- to 12-membered bicyclic rings. Each ring of a bicyclic carbocycle may be selected from saturated, unsaturated, and aromatic rings. Bicyclic carbocycles may be fused, bridged or spiro-ring systems. In some embodiments, the bicyclic carbocycle is selected from fused carbocycle, bridged carbocycle, and spirocyclic carbocycle. In some embodiments, the carbocycle is an aryl. In some embodiments, the carbocycle is a cycloalkyl. In some embodiments, the carbocycle is a cycloalkenyl. In an exemplary embodiment, an aromatic ring, e.g., phenyl, may be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated and aromatic bicyclic rings, as valence permits, are included in the definition of carbocyclic. Exemplary carbocycles include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, indanyl, and naphthyl. Carbocycle may be optionally substituted by one or more substituents such as those substituents described herein.

[0034] The term “carbocyclene” as used herein refers to a divalent saturated, unsaturated or aromatic ring in which each atom of the ring is carbon. The carbocyclene is attached to the rest of the molecule through a single bond and to the radical group through a single bond. A carbocyclene may be optionally substituted by one or more substituents such as those substituents described herein. Carbocyclene includes divalent 3- to 10-membered monocyclic rings and divalent polycyclic rings (e.g., 6- to 12-membered bicyclic rings). Each ring of a polycyclic carbocyclene may be selected from saturated, unsaturated, and aromatic rings.Polycyclic carbocyclenes may be fused, bridged or spiro-ring systems. Polycyclic carbocyclenes may be fused, bridged or spiro-ring systems. The single bond connecting the carbocyclene to the rest of the molecule and the single bond connecting the carbocyclene to the radical group may be located on two different carbon atoms of the carbocyclene. The single bond connecting the carbocyclene to the rest of the molecule and the single bond connecting the carbocyclene to the radical group may be located on the same carbon atom of the carbocyclene. The single bond connecting the carbocyclene to the rest of the molecule and the single bond connecting the carbocyclene to the radical group may be located on the same ring or different rings of a polycyclic carbocyclene. In some embodiments, the carbocycle is an arylene, for example, a phenylene. A “phenylene” as used herein refers to a divalent benzene group. The phenylene is attached to the rest of the molecule through a single bond and to the radical group through a single bond. A phenylene may be optionally substituted by one or more substituents such as those substituents described herein.

[0035] "Cycloalkyl" refers to a stable fully saturated monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, which includes fused or bridged ring systems, and preferably having from three to twelve carbon atoms (i.e., C3-12cycloalkyl). In certain embodiments, a cycloalkyl comprises three to ten carbon atoms (i.e., C3-10cycloalkyl). In other embodiments, a cycloalkyl comprises five to seven carbon atoms (i.e., C5-7 cycloalkyl). The cycloalkyl may be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkyls include, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyl radicals include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptanyl), norbornenyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like. Cycloalkyl may be optionally substituted by one or more substituents such as those substituents described herein.

[0036] "Cycloalkenyl" refers to a stable unsaturated non-aromatic monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, which includes fused or bridged ring systems, preferably having from three to twelve carbon atoms and comprising at least one double bond (i.e., C3-12 cycloalkenyl). In certain embodiments, a cycloalkenyl comprises three to ten carbon atoms (i.e., C3-10cycloalkenyl). In other embodiments, a cycloalkenyl comprises five to seven carbon atoms (i.e., C5-7cycloalkenyl). The cycloalkenyl may be attached to the rest of the molecule by a single bond. Examples of monocyclic cycloalkenyls include, e.g., cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Cycloalkenyl may be optionally substituted by one or more substituents such as those substituents described herein.

[0037] "Aryl" refers to a radical derived from an aromatic monocyclic or aromatic multicyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or aromatic multicyclic hydrocarbon ring system contains only hydrogen and carbon and from five to eighteen carbon atoms, where at least one of the rings in the ring system is aromatic, i.e., it contains a cyclic, delocalized (4n+2) ^–electron system in accordance with the Hückel theory. The ring system from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin and naphthalene. Aryl may be optionally substituted by one or more substituents such as those substituents described herein.

[0038] A “Cx-ycarbocycle” is meant to include groups that contain from x to y carbons in a ring. For example, the term “C3-6carbocycle” can be a saturated, unsaturated or aromatic ring system that contains from 3 to 6 carbon atoms―any of which is optionally substituted as provided herein.

[0039] The term “heterocycle” as used herein refers to a saturated, unsaturated, non-aromatic or aromatic ring comprising one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycles include 3- to 10-membered monocyclic rings and 6- to 12- membered bicyclic rings. Each ring of a bicyclic heterocycle may be selected from saturated, unsaturated, and aromatic rings. In some embodiments, the heterocycle comprises at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocycle comprises at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heterocycle comprises at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heterocycle comprises at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. The heterocycle may be attached to the rest of the molecule through any atom of the heterocycle, valence permitting, such as a carbon or nitrogen atom of the heterocycle. In some embodiments, the heterocycle is a heteroaryl. In some embodiments, the heterocycle is a heterocycloalkyl. Exemplary heterocycles include pyrrolidinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, piperidinyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, thiophenyl, oxazolyl, thiazolyl, morpholinyl, indazolyl, indolyl, and quinolinyl. Heterocycle may be optionally substituted by one or more substituents such as those substituents described herein. Bicyclic heterocycles may be fused, bridged or spiro-ring systems. In an exemplary embodiment, a heterocycle, e.g., pyridyl, may be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Heterocycle may be optionally substituted by one or more substituents such as those substituents described herein.

[0040] The term “heterocyclene” as used herein refers to a divalent saturated, unsaturated, non-aromatic or aromatic ring comprising one or more heteroatoms. Exemplary heteroatomsinclude N, O, Si, P, B, and S atoms. The heterocyclene is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The single bond attaching the heterocyclene group to the rest of the molecule and the single bond attaching the heterocyclene group to the radical group may be each independently connected through any atom of the heterocyclene as valency permits, including a carbon atom in the heterocyclene ring or a heteroatom in the heterocyclene ring. A heterocyclene may be optionally substituted by one or more substituents such as those substituents described herein. Heterocyclenes include 3- to 10-membered monocyclic rings and polycyclic rings (e.g., 6- to 12-membered bicyclic rings). Each ring of a polycyclic heterocyclene may be selected from saturated, unsaturated, and aromatic rings. Polycyclic heterocyclenes may be fused, bridged or spiro-ring systems. The single bond connecting the heterocyclene to the rest of the molecule and the single bond connecting the heterocyclene to the radical group may be located on two different carbon atoms of the heterocyclene. The single bond connecting the heterocyclene to the rest of the molecule and the single bond connecting the heterocyclene to the radical group may be located on the same carbon atom of the heterocyclene. The single bond connecting the heterocyclene to the rest of the molecule and the single bond connecting the heterocyclene to the radical group may be located on the same ring or different rings of a polycyclic heterocyclene and may be attached to the rest of the molecule or the radical group through any atom of the heterocyclene, valence permitting, such as a carbon or nitrogen atom of the heterocycle. In some embodiments, the heterocyclene comprises at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocyclene comprises at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heterocyclene comprises at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heterocyclene comprises at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocyclene is a heteroarylene. In some embodiments, the heterocyclene is a heterocycloalkylene.

[0041] "Heterocycloalkyl" refers to a stable 3- to 12-membered non-aromatic ring radical that comprises two to twelve carbon atoms and at least one heteroatom wherein each heteroatom may be selected from N, O, Si, P, B, and S atoms. In some embodiments, the heterocycloalkyl comprises at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocycloalkyl comprises at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heterocycloalkyl comprises at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heterocycloalkyl comprises at least one heteroatom selected fromnitrogen, sulfur, or any combination thereof. The heterocycloalkyl may be selected from monocyclic or bicyclic, and fused or bridged ring systems. The heteroatoms in the heterocycloalkyl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heterocycloalkyl radical is partially or fully saturated. The heterocycloalkyl is attached to the rest of the molecule through any atom of the heterocycloalkyl, valence permitting, such as any carbon or nitrogen atoms of the heterocycloalkyl. Examples of heterocycloalkyl radicals include, but are not limited to, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Heterocycloalkyl may be optionally substituted by one or more substituents such as those substituents described herein.

[0042] The term “heteroaryl” refers to a radical derived from a 5- to 12-membered aromatic ring radical whose ring structure comprise at least one heteroatom, preferably between one to four heteroatoms. In some embodiments, the heteroaryl comprises at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heteroaryl comprises at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heteroaryl comprises at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heteroaryl comprises at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. One or more nitrogen atoms, if present, are optionally quaternized. The heteroaryl may be attached to the rest of the molecule through any atom of the heteroaryl, valence permitting, such as a carbon or nitrogen atom of the heteroaryl.

[0043] As used herein, the heteroaryl ring may be selected from monocyclic or polycyclic (bicyclic and fused or bridged) systems rings wherein at least one of the rings in the ring system is aromatic, i.e., it contains a cyclic, delocalized (4n+2) ^–electron system in accordance with the Hückel theory. Heteroaryl includes aromatic single ring structures, preferably 5- to 6- membered rings, whose ring structures include at least one heteroatom, preferably one to four heteroatoms, more preferably one or two heteroatoms. Heteroaryl groups include, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine, and the like. Heteroaryl may be optionally substituted by one or more substituents such as those substituents described herein. Heteroaryl also includes polycyclic ring systems having two or more rings in which two or more atoms are common to two adjoiningrings wherein at least one of the rings is heteroaromatic, e.g., the other rings can be aromatic or non-aromatic carbocyclic, or heterocyclic.

[0044] An “X-membered heterocycle” refers to the number of endocylic atoms, i.e., X, in the ring. For example, a 5-membered heteroaryl ring or 5-membered aromatic heterocycle has 5 endocyclic atoms, e.g., triazole, oxazole, thiophene, etc.

[0045] "Alkoxy" refers to a radical bonded through an oxygen atom of the formula –O-alkyl, where alkyl is an alkyl chain as defined above.

[0046] "Halo" or "halogen" refers to halogen substituents such as bromo, chloro, fluoro and iodo substituents.

[0047] As used herein, the term "haloalkyl" or “haloalkane” refers to an alkyl radical, as defined above, that is substituted by one or more halogen radicals, for example, trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, and the like. In some embodiments, the alkyl part of the fluoroalkyl radical is optionally further substituted. Examples of halogen substituted alkanes (“haloalkanes”) include halomethane (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), di-and trihalomethane (e.g., trichloromethane, tribromomethane, trifluoromethane, triiodomethane), 1-haloethane, 2- haloethane, 1,2-dihaloethane, 1-halopropane, 2-halopropane, 3-halopropane, 1,2-dihalopropane, 1,3-dihalopropane, 2,3-dihalopropane, 1,2,3-trihalopropane, and any other suitable combinations of alkanes (or substituted alkanes) and halogens (e.g., Cl, Br, F, and I). When an alkyl group is substituted with more than one halogen radicals, each halogen may be independently selected for example, 1-chloro,2-fluoroethane.

[0048] The term “substituted” refers to moieties having substituents replacing a hydrogen on one or more carbons or substitutable heteroatoms, e.g., an NH or NH2of a compound. It will be understood that “substitution” or “substituted with” includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, i.e., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. In certain embodiments, substituted refers to moieties having substituents replacing two hydrogen atoms on the same carbon atom, such as substituting the two hydrogen atoms on a single carbon with an oxo, imino or thioxo group. As used herein, the term “substituted” is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different for appropriate organic compounds.

[0049] In some embodiments, substituents may include any substituents described herein, for example: halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo (=N-OH), hydrazino (=N-NH2), -Rb-ORa, -Rb-OC(O)-Ra, -Rb-OC(O)-ORa, -Rb-OC(O)- N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, -Rb- N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb-N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2), and -Rb-S(O)tN(Ra)2 (where t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl any of which may be optionally substituted by alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=N-H), oximo(=N-OH), hydrazine(=N-NH2), -Rb-ORa, -Rb-OC(O)- Ra, -Rb-OC(O)- ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb- C(O)N(Ra)2, -Rb-O-Rc-C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb-N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2) and -Rb-S(O)tN(Ra)2 (where t is 1 or 2); wherein each Rais independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, wherein each Ra, valence permitting, may be optionally substituted with alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (- CN), nitro (-NO2), imino (=N-H), oximo (=N-OH), hydrazine(=N-NH2), -Rb-ORa, -Rb-OC(O)- Ra, -Rb-OC(O)-ORa, -Rb-OC(O)-N(Ra)2, -Rb-N(Ra)2, -Rb-C(O)Ra, -Rb-C(O)ORa, -Rb-C(O)N(Ra)2, -Rb-O-Rc- C(O)N(Ra)2, -Rb-N(Ra)C(O)ORa, -Rb-N(Ra)C(O)Ra, -Rb-N(Ra)S(O)tRa(where t is 1 or 2), -Rb-S(O)tRa(where t is 1 or 2), -Rb-S(O)tORa(where t is 1 or 2) and -Rb-S(O)tN(Ra)2(where t is 1 or 2); and wherein each Rbis independently selected from a direct bond or a straight or branched alkylene, alkenylene, or alkynylene chain, and each Rcis a straight or branched alkylene, alkenylene or alkynylene chain. It will be understood by those skilled in the art that substituents can themselves be substituted, if appropriate.

[0050] The term “salt” or “pharmaceutically acceptable salt” refers to salts derived from a variety of organic and inorganic counter ions well known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases.

[0051] The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0052] The phrase “pharmaceutically acceptable excipient” or “pharmaceutically acceptable carrier” as used herein means a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient.

[0053] The terms "subject," "individual," and "patient" may be used interchangeably and refer to humans, the as well as non-human mammals (e.g., non-human primates, canines, equines, felines, porcines, bovines, ungulates, lagomorphs, and the like). In various embodiments, the subject can be a human (e.g., adult male, adult female, adolescent male, adolescent female, male child, female child) under the care of a physician or other health worker in a hospital, as an outpatient, or other clinical context. In certain embodiments, the subject may not be under the care or prescription of a physician or other health worker.

[0054] As used herein, the phrase "a subject in need thereof" refers to a subject, as described infra, that suffers from, or is at risk for, a pathology to be prophylactically or therapeutically treated with a compound or salt described herein.

[0055] The terms “administer”, “administered”, “administers” and “administering” are defined as providing a composition to a subject via a route known in the art, including but not limited to intravenous, intraarterial, oral, parenteral, buccal, topical, transdermal, rectal, intramuscular, subcutaneous, intraosseous, transmucosal, or intraperitoneal routes of administration. In certain embodiments, oral routes of administering a composition can be used. The terms “administer”, “administered”, “administers” and “administering” a compound should be understood to mean providing a compound of the invention or a prodrug of a compound of the invention to the individual in need.

[0056] As used herein, “treatment” or “treating” refers to an approach for obtaining beneficial or desired results with respect to a disease, disorder, or medical condition including, but not limited to, a therapeutic benefit and / or a prophylactic benefit. In certain embodiments, treatment or treating involves administering a compound or composition disclosed herein to a subject. A therapeutic benefit may include the eradication or amelioration of the underlying disorder being treated. Also, a therapeutic benefit may be achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder, such asobserving an improvement in the subject, notwithstanding that the subject may still be afflicted with the underlying disorder. In certain embodiments, for prophylactic benefit, the compositions are administered to a subject at risk of developing a particular disease, or to a subject reporting one or more of the physiological symptoms of a disease, even though a diagnosis of this disease may not have been made. Treating can include, for example, reducing, delaying or alleviating the severity of one or more symptoms of the disease or condition, or it can include reducing the frequency with which symptoms of a disease, defect, disorder, or adverse condition, and the like, are experienced by a patient. Treating can be used herein to refer to a method that results in some level of treatment or amelioration of the disease or condition and can contemplate a range of results directed to that end, including but not restricted to prevention of the condition entirely.

[0057] As used herein, “PF-06873600” is a competitor molecule. In some embodiments, the competitor molecule is molecule represented by the structure of(PF-06873600). In some embodiments, PF-06873600 is. In some embodiments, the competitor molecule is 6- (difluoromethyl)-8-((1R,2R)-2-hydroxy-2-methylcyclopentyl)-2-((1-(methylsulfonyl)piperidin- 4-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one (PF-06873600).

[0058] In certain embodiments, the term “prevent” or “preventing” as related to a disease or disorder may refer to a compound that, in a statistical sample, reduces the occurrence of the disorder or condition in the treated sample relative to an untreated control sample, or delays the onset or reduces the severity of one or more symptoms of the disorder or condition relative to the untreated control sample. Compounds

[0059] In some aspects, the present disclosure provides a compound represented by the structure of Formula (I)or a pharmaceutically acceptable salt thereof wherein: Ring A is selected from C3-12 carbocycle and 3- to 12-membered heterocycle; R5is selected from an electrophilic moiety or a prodrug thereof; each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, - S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, - SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; L is represented by -L1- L2-L3-L4-, wherein L1, L2, L3, and L4are each independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, - (R12)NC(O)N(R12)-, and–-(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN;wherein L2, L3, and L4are each optionally absent; wherein no more than two of L1, L2, L3, and L4are selected from (a) and the two selected are not adjacent; R1and R2are each independently selected from (i), (ii), and (iii): (i) hydrogen, -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -C(O)OR14, -OC(O)R14, - N(R14)C(O)OR14, N(R14)C(O)R14, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, and -CN; (ii) C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), - CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; orR1and R2may come together to form a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, - C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, -N(R15)C(O)N(R15)2, - S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, -N(R15)C(O)N(R15)2, - S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN; R3is selected from: hydrogen, halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -C(O)OR16, -NO2, - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -C(O)OR16, - NO2, and -CN; R11, R12, R13, R14, R15, and R16are each independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted with one more substituents independently selected from halogen, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,-NO2, =O, -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein each C3-10carbocycle and 3- to 10-membered heterocycle are optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,-NO2, =O, and -CN; and C3-6carbocycle and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,-NO2, =O, and -CN; n is selected from 0, 1, 2, 3, and 4; and m is selected from 0 and 1.

[0060] In some embodiments, for the compound or salt of Formula (I), the electrophilic moiety is a lysine reactive electrophile. In some embodiments, the lysine reactive electrophile is selected from a reversible lysine reactive electrophile and an irreversible lysine reactive electrophile.

[0061] In some embodiments, for the compound or salt of Formula (I), the electrophilic moiety is selected from a haloacetamide, a haloalkyl ketone, a halo amidine, a halo benzylphosphonate,an acyloxyalkyl ketone, a sulfonyl oxirane, an epoxide, a diazoalkyl ketone, a halotriazine, an acrylamide, a cyano acrylamide, a vinyl sulfone, a vinyl sulfonamide, an acrylate, an aldehyde, a borate, a halosulfonyl, an ester, squaric ester, squaramide ester, a fumarate, a carbonyl acrylate, a maleimide, a ketoamide, a nitrile, an alkene, an alkyne, a keto heterocycle, and an ynamide. In some embodiments, the electrophilic moiety is selected from a haloacetamide, a haloalkyl ketone, a halo amidine, a halo benzylphosphonate, an acyloxyalkyl ketone, a sulfonyl oxirane, an epoxide, a diazoalkyl ketone, a halotriazine, an acrylamide, a cyano acrylamide, a vinyl sulfone, a vinyl sulfonamide, an acrylate, a fumarate, a carbonyl acrylate, a maleimide, a ketoamide, a nitrile, an alkene, an alkyne, a keto heterocycle, and an ynamide. In some embodiments, the electrophilic moiety is selected an aldehyde, a borate, and a halosulfonyl.

[0062] In some embodiments, for the compound or salt of Formula (I), the electrophilic moiety or prodrug thereof is an aldehyde or a prodrug thereof. In some embodiments, the electrophilic moiety or prodrug thereof of R5is an aldehyde or a prodrug thereof. In some embodiments, the electrophilic moiety or prodrug thereof of R5is an aldehyde.

[0063] In some embodiments, for the compound or salt of Formula (I), the aldehyde or a prodrug thereof is an imine. In some embodiments, the electrophilic moiety or prodrug thereof of R5is an imine.

[0064] In some embodiments, for the compound or salt of Formula (I), the imine is represented by -C(R17)=N(R18); wherein R17is selected from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR20, -SR20, -N(R20)2, - C(O)R20, -C(O)N(R20)2, -C(O)OR20, -OC(O)R20, -N(R20)C(O)OR20, - N(R20)C(O)R20, -S(O)R20, -S(O)2R20, -N(R20)S(O)2R20, -S(O)2N(R20)2, -NO2, =O, =S, =N(R20) and -CN; R18is selected from: hydrogen; C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, - C(O)N(R21)2, -C(O)OR21, -OC(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)R21, - S(O)R21, -S(O)2R21, -N(R21)S(O)2R21, -S(O)2N(R21)2, -P(=O)(OR21)2, -NO2, =O, =S, =N(R21), -CN, C3-10carbocycle, and 3- to 10- membered heterocycle; and C3-10carbocycle and 3- to 10- membered heterocycle, any of which are optionally substituted with one or more substituents independently selected from halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -C(O)OR21, - OC(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)R21, -S(O)R21, -S(O)2R21, -N(R21)S(O)2R21, -S(O)2N(R21)2, -NO2, =O, =S, =N(R21), -CN, C1-6alkyl, and C1-6haloalkyl; and R20and R21are each independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted with one more substituents independently selected from halogen, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,- NO2, =O, -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein each C3-10carbocycle and 3- to 10-membered heterocycle are optionally substituted with one or more substituents independently selected from: halogen, - OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,-NO2, =O, and -CN; and C3-6carbocycle and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, - OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,-NO2, =O, and -CN.

[0065] In some embodiments, for the compound or salt of Formula (I), R5is an imine.

[0066] In some embodiments, for the compound or salt of Formula (I), R5is -C(R17)=N(R18); R17is selected from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR20, -SR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, - C(O)OR20, -OC(O)R20, -N(R20)C(O)OR20, -N(R20)C(O)R20, -S(O)R20, -S(O)2R20, - N(R20)S(O)2R20, -S(O)2N(R20)2, -NO2, =O, =S, =N(R20) and -CN; R18is selected from: hydrogen; C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -C(O)OR21, - OC(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)R21, -S(O)R21, -S(O)2R21, -N(R21)S(O)2R21, - S(O)2N(R21)2, -P(=O)(OR21)2, -NO2, =O, =S, =N(R21), -CN, C3-10carbocycle, and 3- to 10- membered heterocycle; and C3-10carbocycle and 3- to 10- membered heterocycle, any of which are optionally substituted with one or more substituents independently selected from halogen, -OR21, - SR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -C(O)OR21, -OC(O)R21, -N(R21)C(O)OR21, - N(R21)C(O)R21, -S(O)R21, -S(O)2R21, -N(R21)S(O)2R21, -S(O)2N(R21)2, -NO2, =O, =S, =N(R21), -CN, C1-6alkyl, and C1-6haloalkyl; and R20and R21are each independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted with one more substituents independently selected from halogen, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2, -NO2, =O, -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein each C3-10carbocycle and 3- to 10-membered heterocycle are optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,-NO2, =O, and -CN; and C3-6carbocycle and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2, -NO2, =O, and -CN.

[0067] In certain embodiments, the compound or salt of Formula (I) or (II), is represented by the structure of Formula (wherein Ring A, R1, R2, R3, R4, L, n, R17, and R18are each defined as in Formula (I) or (II).

[0068] In certain embodiments, the compound or salt of Formula (I) or (II), is represented by the structure of Formula (wherein R1, R2, R3, R4, L, n, R17, and R18are each defined as in Formula (I) or (II).

[0069] In certain embodiments, the compound or salt of Formula (I) or (II), is represented by the structure of Formulawherein Ring A is indanyl; and each of R1, R2, R3, R4, L, n, R17, and R18are each defined as in Formula (I) or (II).

[0070] In certain embodiments, the compound or salt of Formula (I) or (II), is represented by the structure of Formula (wherein R1and R2come together to form an optionally substituted a 3- to 10-membered heterocycle represented by; and Ring A, R3, R4, L, n, R17, and R18are each defined as in Formula (I) or (II).

[0071] In certain embodiments, the compound or salt of Formula (I) or (II), is represented by the structure of Formula (wherein Ring A, R1, R2, R3, R4, L, n, R17, and R18are each defined as in Formula (I) or (II).

[0072] In certain embodiments, the compound or salt of Formula (I) or (II), is represented by the structure of Formula (wherein Ring A, R1, R2, R3, R4, L, n, R17, and R18are each defined as in Formula (I) or (II).

[0073] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R17is selected from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR20, -SR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -C(O)OR20, -OC(O)R20, -N(R20)C(O)OR20, -N(R20)C(O)R20, -NO2, =O, and -CN. In some embodiments, R17is selected from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR20, -SR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, -NO2, =O, and -CN. In some embodiments, R17is selected from hydrogen and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, -OR20, -SR20, -N(R20)2, -NO2, and -CN.

[0074] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R17is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, R17is selected from hydrogen, C1-3alkyl, and C1-3haloalkyl. In some embodiments, R17is hydrogen. In some embodiments, R17is C1-6alkyl. In some embodiments, R17is C1-3 alkyl. In some embodiments, R17is C1-6haloalkyl. In some embodiments, R17is C1-3 haloalkyl.

[0075] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R18is hydrogen.

[0076] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R18is C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, - C(O)OR21, -OC(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)R21, -S(O)R21, -S(O)2R21, - N(R21)S(O)2R21, -S(O)2N(R21)2, -P(=O)(OR21)2, -NO2, =O, =S, =N(R21), -CN, C3-10carbocycle, and 3- to 10- membered heterocycle. In some embodiments, R18is C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR21, -N(R21)2, -C(O)R21-C(O)OR21, -OC(O)R21, -S(O)2R21, -P(=O)(OR21)2, -NO2, -CN, C3-10carbocycle, and 3- to 10- membered heterocycle. In some embodiments, R18is C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR21, -P(=O)(OR21)2, -S(O)2R21, -NO2, -CN, C3-6carbocycle, and 3- to 6- membered heterocycle.

[0077] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R18is selected from hydrogen; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -C(O)OR21, -OC(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)R21, -NO2, =O, -CN, C3-10 carbocycle, and 3- to 10- membered heterocycle. In some embodiments, R18is selected from hydrogen; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -NO2, =O, -CN, C3-10carbocycle, and 3- to 10- membered heterocycle. In some embodiments, R18is selected from hydrogen; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR21, -SR21, -N(R21)2, -NO2, -CN, C3-10carbocycle, and 3- to 10- membered heterocycle. In some embodiments, R18is selected from hydrogen; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, - OR21, -SR21, -N(R21)2, -NO2, and -CN.

[0078] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R18is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0079] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C), ,

[0080] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R18is C1-6alkyl substituted with one or more substituents independently selected from -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -C(O)OR21, -OC(O)R21, - N(R21)C(O)OR21, -N(R21)C(O)R21, -S(O)R21, -S(O)2R21, -N(R21)S(O)2R21, -S(O)2N(R21)2, - P(=O)(OR21)2, -NO2, =O, =S, =N(R21), and -CN.

[0081] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R18is C1-6alkyl substituted with one or more substituents independently selected from -OR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -C(O)OR21, -S(O)2R21, -P(=O)(OR21)2, - NO2, =O, and -CN.

[0082] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R18is C1-6alkyl substituted with one or more substituents independently selected from -OR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -C(O)OR21, -S(O)2R21, -P(=O)(OR21)2, - NO2, =O, and -CN, wherein R21is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0083] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C),

[0084] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R18is C1-6alkyl substituted with one or more substituents independently selected from C3-10carbocycle and 3- to 10-membered heterocycle. In some embodiments, R18is C1-6alkyl substituted with one or more substituents independently selected from C3-6carbocycle and 3- to 6-membered heterocycle.

[0085] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R18is C1-6alkyl substituted with one or more C3-6carbocycle. In some embodiments, R18is C1-6alkyl substituted with one or more phenyl.

[0086] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R18is selected from.

[0087] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R18is selected from C3-10carbocycle and 3- to 10-membered heterocycle, any of which are optionally substituted with one or more substituents independently selected from halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -C(O)OR21, -OC(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)R21, -S(O)R21, -S(O)2R21, -N(R21)S(O)2R21, -S(O)2N(R21)2, - NO2, =O, =S, =N(R21), -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments, R18is selected from C3-10carbocycle and 3- to 10-membered heterocycle, any of which are optionally substituted with one or more substituents independently selected from halogen, -OR21, -SR21, - N(R21)2, -C(O)R21, -NO2, =O, =S, =N(R21), -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments, R18is selected from C3-10carbocycle and 3- to 10-membered heterocycle, any of which are optionally substituted with one or more substituents independently selected from halogen, -OR21, -N(R21)2, -C(O)R21, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl.

[0088] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R18is selected from C3-7carbocycle and 3- to 7-membered heterocycle, any of which are optionally substituted with one or more substituents independently selected from halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -C(O)OR21, -OC(O)R21, - N(R21)C(O)OR21, -N(R21)C(O)R21, -S(O)R21, -S(O)2R21, -N(R21)S(O)2R21, -S(O)2N(R21)2, -NO2, =O, =S, =N(R21), -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments, R18is selected from C3-7 carbocycle and 3- to 7-membered heterocycle, any of which are optionally substituted with one or more substituents independently selected from halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -NO2, =O, =S, =N(R21), -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments, R18is selected from C3-7 carbocycle and 3- to 7-membered heterocycle, any of which are optionally substituted with one or more substituents independently selected from halogen, -OR21, -N(R21)2, -C(O)R21, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl.

[0089] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R18is selected from C3-6carbocycle and 3- to 6-membered heterocycle, any of which are optionally substituted with one or more substituents selected from halogen, - OR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -C(O)OR21, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments, R18is selected from C3-6carbocycle and 3- to 6-membered heterocycle, any of which are optionally substituted with one or more substituents selected from halogen, -OR21, -N(R21)2, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl. In some embodiments, R18is selected from C3-6carbocycle and 3- to 6-membered heterocycle. In some embodiments, R18is C3-6carbocycle.

[0090] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C),

[0091] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C),

[0092] In some embodiments, for the compound or salt of Formula (II), (II-A), (II-B), (II-C),

[0093] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), wherein m is 1.

[0094] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), wherein m is 2.

[0095] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R3is selected from hydrogen and C1-6alkyl and C1-6haloalkyl. In some embodiments, wherein R3is hydrogen.

[0096] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R4is independently selected from halogen, -OR11, -N(R11)2, -NO2, -CN,C1-6alkyl, and C1-6haloalkyl. In some embodiments, R4is selected from -OH, -OMe, and methyl.

[0097] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), n is selected from 1 and 2.

[0098] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), n is 1.

[0099] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), n is 2.

[0100] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), n is 3.

[0101] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), Ring A is selected from C3-8carbocycle and 3- to 8-membered heterocycle. In some embodiments, Ring A is C3-8carbocycle. In some embodiments, Ring A is phenyl.

[0102] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), or (II-D), Ring A is C3-12carbocycle. In some embodiments, Ring A is C3-12saturated carbocycle. In some embodiments, Ring A is C3-12 unsaturated carbocycle. In some embodiments, Ring A is C6-12 aryl. In some embodiments, Ring A is selected from C3 carbocycle, C4 carbocycle, C5 carbocycle, C6carbocycle, C7carbocycle, C8carbocycle, C9carbocycle, C10carbocycle, C11carbocycle, and C12carbocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, Ring A is selected from C3-4 carbocycle, C3-5 carbocycle, C3-6carbocycle, C3-7carbocycle, C3-8carbocycle, C3-9carbocycle, C3-10carbocycle, C3-11carbocycle, and C3-12carbocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, Ring A is selected from C3-8 monocyclic carbocycle and C4-12 bicyclic carbocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, the C3-8monocyclic carbocycle of Ring A is selected from C3-8cycloalkyl and phenyl, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, the C4-12 bicyclic carbocycle of Ring A is selected from C4-12 fused carbocycle, C4-12bridged carbocycle, and C4-12spirocyclic carbocycle, each of which is optionally substituted with R4as defined in Formula (I).

[0103] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), or (II-D), Ring A is 3- to 12-membered heterocycle. In some embodiments, Ring A is 3- to 12-membered heterocycle comprising at least one heteroatom selected from oxygen, nitrogen, and sulfur. In some embodiments, Ring A is 3- to 12-membered unsaturated heterocycle. In some embodiments, Ring A is 3- to 12-membered heteroaryl. In some embodiments, Ring A isselected from 3-membered heterocycle, 4-membered heterocycle, 5-membered heterocycle, 6- membered heterocycle, 7-membered heterocycle, 8-membered heterocycle, 9-membered heterocycle, 10-membered heterocycle, and 11-membered heterocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, Ring A is selected from 3- to 4-membered heterocycle, 3- to 5-membered heterocycle, 3- to 6-membered heterocycle, 3- to 7-membered heterocycle, 3- to 8-membered heterocycle, 3- to 9-membered heterocycle, 3- to 10-membered heterocycle, 3- to 11-membered heterocycle, and 3- to 12- membered heterocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, Ring A is selected from 3- to 8-membered monocyclic heterocycle and 4- to 12-membered bicyclic heterocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, Ring A is selected from 3- to 8-membered monocyclic heterocycle and 8- to 12-membered bicyclic heterocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, Ring A is selected from 3- to 8- membered monocyclic heterocycle and 8- to 12-membered bicyclic heterocycle. In some embodiments, the 4- to 12-membered bicyclic heterocycle is selected from 4- to 12-membered fused heterocycle, 4- to 12-membered bridged heterocycle, and 4- to 12-membered spirocyclic heterocycle, each of which is optionally substituted with R4as defined in Formula (I).

[0104] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), or (II-D), Ring A is selected from C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, Ring A is C3-10carbocycle optionally substituted with R4as defined in Formula (I). In some embodiments, Ring A is 3- to 10-membered heterocycle optionally substituted with R4as defined in Formula (I).

[0105] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), or (II-D), Ring A is selected from C3-10carbocycle and 3- to 10-membered heterocycle. In some embodiments, Ring A is C6-10 carbocycle. In some embodiments, Ring A is a bicyclic C6-10 carbocycle. In some embodiments, the bicyclic C6-10carbocycle of Ring A is selected from C6-10fused carbocycle, C6-10bridged carbocycle, and C6-10spirocyclic carbocycle. In some embodiments, Ring A is C6-10 fused carbocycle. In some embodiments, Ring A is C6-10 bridged carbocycle. In some embodiments, Ring A is C6-10spirocyclic carbocycle. In some embodiments, Ring A is dihydroindenyl. In some embodiments, Ring A is indanyl. In some embodiments, Ring.

[0106] In some embodiments, for the compound or salt of Formula (I) or (II), wherein.

[0107] In some embodiments, for the compound or salt of Formula (.

[0108] In some embodiments, for the compound or salt of Formula (is selected from

[0109] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), or (II- C), one of R1and R2is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl, and the other is selected from: -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -CN, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from halogen, - OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -NO2, =O, and -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which are optionally substituted with halogen, -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -NO2, =O, - CN, C1-6alkyl, and C1-6haloalkyl.

[0110] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), or (II- C), one of R1and R2is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl, and the other is selected from: -OR14, -N(R14)2, C1-6alkyl, and C2-6alkynyl, wherein the C1-6alkyl and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from halogen, -OR14, -N(R14)2, and -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which are optionally substituted with halogen, C1-6alkyl, and C1-6haloalkyl.

[0111] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), or (II- C), one of R1and R2is selected from hydrogen, methyl, ethyl, and propyl, and the other is selected from methyl, ethyl, propyl,

[0112] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), R1and R2come together to form a 3- to 10-membered heterocycleoptionally substituted with one or more substituents independently selected from halogen, - OR15, -N(R15)2, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl.

[0113] In some embodiments, for the compound or salt of Formula (I) or (II),is selected from

[0114] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), any of L1, L2, L3, or L4is independently selected from C3-12 carbocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from C3-12unsaturated carbocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from C3-12 arylene. In some embodiments, any of L1, L2, L3, or L4is independently selected from C3 carbocyclene, C4 carbocyclene, C5 carbocyclene, C6 carbocyclene, C7 carbocyclene, C8carbocyclene, C9carbocyclene, C10carbocyclene, and C11carbocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from C3-4carbocyclene, C3-5 carbocyclene, C3-6carbocyclene, C3-7 carbocyclene, C3-8 carbocyclene, C3-9 carbocyclene, C3-10carbocyclene, C3-11 carbocyclene, and C3-12 carbocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected C3-8monocyclic carbocyclene and C8-12bicyclic carbocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from C3-8 monocyclic carbocyclene and C4-12 bicyclic carbocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from C3-8monocyclic carbocyclene and C8-12bicyclic carbocyclene. In some embodiments, the C4-12 carbocyclene is selected from C4-12 carbocyclene, C4-12 bridged carbocyclene, and C4-12 spirocyclic carbocyclene.

[0115] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), any of L1, L2, L3, or L4is independently selected from 3- to 12- membered heterocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from 3- to 12-membered heterocyclene comprising at least one heteroatom selected from oxygen, nitrogen, and sulfur. In some embodiments, any of L1, L2, L3, or L4is independently selected from 3- to 12-membered unsaturated heterocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from 3- to 12-membered heteroarylene. In some embodiments, any of L1, L2, L3, or L4is independently selected from 3- membered heterocyclene, 4-membered heterocyclene, 5-membered heterocyclene, 6-membered heterocyclene, 7-membered heterocyclene, 8-membered heterocyclene, 9-membered heterocyclene, 10-membered heterocyclene, and 11-membered heterocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from 3- to 4-membered heterocyclene, 3- to 5-membered heterocyclene, 3- to 6-membered heterocyclene, 3- to 7-membered heterocyclene, 3- to 8-membered heterocyclene, 3- to 9-membered heterocyclene, 3- to 10-membered heterocyclene, 3- to 11-membered heterocyclene, and 3- to 12-membered heterocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from 3- to 8-membered monocyclic heterocyclene and 4- to 12-membered bicyclic heterocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from 3- to 8-membered monocyclic heterocyclene and 8- to 12-membered bicyclic heterocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from 3- to 8-membered monocyclic heterocyclene and 8- to 12-membered bicyclic heterocyclene. In some embodiments, the 4- to 12-membered bicyclic heterocyclene is selected from 4- to 12-membered fused heterocyclene, 4- to 12-membered bridged heterocyclene, and 4- to 12-membered spirocyclic heterocyclene.

[0116] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), each of L2, L3and L4are absent and L1is selected from (a) and (b): (a) - O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, - N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, - N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN. In some embodiments, each of L2, L3and L4are absent and L1is selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, - S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and - (R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, and C2-6alkynylene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN. In some embodiments, each of L2, L3and L4are absent and L1is selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, - S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and - (R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle,wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN.

[0117] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), each of L2, L3and L4are absent and L1is selected from (a) and (b): (a) - N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN. In some embodiments, each of L2, L3and L4are absent and L1is selected from (a) and (b):(a) -N(R12)C(O)-, - N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN. In some embodiments, each of L2, L3and L4are absent and L1is selected from (a) and (b): (a) -N(R12)C(O)-, -N(R12)C(O)C(O)N(R12)-, and - (R12)NC(O)N(R12)-; and (b) C1-6alkylene which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN. In some embodiments, each of L2, L3and L4are absent and L1is selected from -N(R12)C(O)-, - N(R12)C(O)C(O)N(R12)-, and -(R12)NC(O)N(R12)-; and R12is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0118] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), each of L2, L3and L4are absent and L1is selected from (a) and (b): (a) - N(R12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and - (R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and - CN. In some embodiments, each of L2, L3and L4are absent and L1is selected from (a) and (b):(a) -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and - (R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN. In some embodiments, each of L2, L3and L4are absent and L1is selected from (a) and (b): (a) -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)C(O)N(R12)-, and -(R12)NC(O)N(R12)-; and (b) C1-6alkylene which is optionally substituted with one or more substituents independently selected from halogen, - OR13, -SR13, =O, =S, -CN. In some embodiments, each of L2, L3and L4are absent and L1is selected from -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)C(O)N(R12)-, and -(R12)NC(O)N(R12)-; and R12is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0119] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), L1is selected from -N(R12)C(O)-, -N(R12)C(O)O-, - N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, - N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and R12is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, L1is selected from -N(R12)C(O)-, -N(R12)C(O)C(O)N(R12)-, and -(R12)NC(O)N(R12)-; and R12is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0120] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), L1is selected from -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)O-, - N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, - N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and R12is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, L1is selected from -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)C(O)N(R12)-, and -(R12)NC(O)N(R12)-; and R12is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0121] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, - N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN. In some embodiments, each of L3and L4are absent and each of L1and L2is selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, - N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, - N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, and C2-6alkynylene, any one of which is optionally substituted with one or moresubstituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN. In some embodiments, each of L3and L4are absent and each of L1and L2is selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, - N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, - N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN.

[0122] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, and -(R12)NC(O)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN. In some embodiments, each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, -N(R12)C(O)-, and -N(R12)C(O)O-; and (b) C1-6alkylene and C2-6alkenylene, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN. In some embodiments, each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, - N(R12)C(O)-, and -N(R12)C(O)O-; and (b) C1-6alkylene and C2-6alkenylene, each of which is optionally substituted with one or more substituents independently selected from halogen, - OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0123] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, - N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C3-10carbocyclene and 3- to 10-membered heterocyclene, any one of which is optionallysubstituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)O-, and - (R12)NC(O)N(R12)-; and (b) C3-10carbocyclene and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0124] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, - N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C3-10carbocyclene optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -N(R12)-, - N(R12)C(O)-, -N(R12)C(O)O-, and -(R12)NC(O)N(R12)-; and (b) C3-10carbocyclene optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)O-, and - (R12)NC(O)N(R12)-; and (b) C3-6saturated carbocyclene optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0125] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, - N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) 3- to 10-membered heterocyclene optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -N(R12)-, - N(R12)C(O)-, -N(R12)C(O)O-, and -(R12)NC(O)N(R12)-; and (b) 3- to 10-membered heterocyclene optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0126] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)O-, and -(R12)NC(O)N(R12)-; and (b) 3- to 6-membered saturated heterocyclene and 3- to 6-membered unsaturated heterocyclene optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0127] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)O-, and -(R12)NC(O)N(R12)-; and (b) 5- to 6-membered heteroarylene and 6- to 10-membered bicyclic heterocyclene optionally substituted with one or more substituents independently selected from halogen, - OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, - OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0128] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), L4is absent and each of L1, L2, and L3are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -N(R12)C(O)-, and -N(R12)C(O)O-; and (b) C1-6alkylene optionally substituted with one or more substituents independently selected from halogen, -OR13, -N(R13)2, and -CN.

[0129] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), L is selected from.

[0130] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C),

[0131] In some embodiments, for the compound or salt of Formula (I), the electrophilic moiety or prodrug thereof is an aldehyde or a prodrug thereof.

[0132] In some embodiments, for the compound or salt of Formula (I), the aldehyde or a prodrug thereof is an aldehyde.

[0133] In some embodiments, for the compound or salt of Formula (I), R5is an aldehyde. In some embodiments, R5is -C(O)H.

[0134] In some embodiments, the compound or salt of Formula (I) is represented by the structure of Formula (III):or a pharmaceutically acceptable salt thereof wherein: Ring A is selected from C3-12carbocycle and 3- to 12-membered heterocycle, each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, - S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, - SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; L is represented by -L1- L2-L3-L4-, wherein L1, L2, L3, and L4are each independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, - (R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN; wherein L2, L3, and L4are each optionally absent; wherein no more than two of L1, L2, L3, and L4are selected from (a) and the two selected are not adjacent; R1and R2are each independently selected from (i), (ii), and (iii): (i) hydrogen, -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -C(O)OR14, -OC(O)R14, - N(R14)C(O)OR14, N(R14)C(O)R14, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, and -CN; (ii) C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), - CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; or R1and R2may come together to form a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, - C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, -N(R15)C(O)N(R15)2, - S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, -N(R15)C(O)N(R15)2, - S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN; R3is selected from: hydrogen, halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -C(O)OR16, -NO2, - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -C(O)OR16, - NO2, and -CN; R11, R12, R13, R14, R15, and R16are each independently selected at each occurrence from:hydrogen; C1-6alkyl optionally substituted with one more substituents independently selected from halogen, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,-NO2, =O, -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein each C3-10carbocycle and 3- to 10-membered heterocycle are optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,-NO2, =O, and -CN; and C3-6carbocycle and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,-NO2, =O, and -CN; n is selected from 0, 1, 2, 3, and 4; and m is selected from 0 and 1.

[0135] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), or (III), R1and R2are each independently selected from hydrogen, -OR14, -N(R14)2, - C(O)R14, -C(O)N(R14)2, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, N(R14)C(O)R14, -S(O)R14, - S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, and -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, - S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, R1and R2are each independently selected from hydrogen, -OR14, -N(R14)2, - C(O)R14, -C(O)N(R14)2, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, N(R14)C(O)R14, -S(O)R14, - S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, and -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl. In some embodiments, R1and R2are each independently selected from hydrogen, - OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, N(R14)C(O)R14, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -CN, and C1-6alkyl.

[0136] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), or (III), R1and R2are each independently selected from R1and R2are each independently selected from hydrogen, -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -C(O)OR14, -OC(O)R14, - N(R14)C(O)OR14, N(R14)C(O)R14, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, and - CN; and R14is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, R1and R2are each independently selected from R1and R2are each independently selected from hydrogen, -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, N(R14)C(O)R14, -S(O)R14, -S(O)2R14, - N(R14)S(O)2R14, -S(O)2N(R14)2, and -CN. In some embodiments, for the compound or salt ofFormula (I), (II), or (III), R1and R2are each independently selected from hydrogen, -OR14, - N(R14)2, -C(O)R14, -C(O)N(R14)2, and -CN. In some embodiments, R1and R2are each independently selected from hydrogen, -OR14, and -N(R14)2; and each R14is independently selected from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, R1and R2are each independently selected from -OR14and -N(R14)2; and each R14is independently selected from hydrogen, C1-3alkyl, and C1-3haloalkyl. In some embodiments, R1and R2are each independently selected from -OH, -OMe, -NMe2, and. In some embodiments, R1and R2are each independently selected from hydrogen, -OH, -OMe, -NMe2, and. In some embodiments, R1and R2are each independently selected from hydrogen, -OH, -OMe, -some embodiments, , R1and R2are each independently selected from, , ,

[0137] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), or (III), R1and R2are each independently selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, - S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, - S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, R1and R2are each independently selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, - S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN.

[0138] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), or (III), one of R1and R2is selected from hydrogen and C1-6alkyl and the other is selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, - C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, - NO2, =O, =S, =N(R14), and -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, - OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, - N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, - N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, - NO2, =O, =S, =N(R14), and -CN. In some embodiments, one of R1and R2is selected from hydrogen and C1-6alkyl and the other is selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, - OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, - N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, one of R1and R2is selected from hydrogen and C1-6alkyl and the other is selected from C2-6alkynyl optionally substituted with one or more substituents independently selected from halogen, - OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, - N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, one of R1and R2is selected from hydrogen and C1-6alkyl and the other is selected from C2-6alkynyl optionally substituted with one or more substituents independently selected from halogen, -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -C(O)OR14, -OC(O)R14, -N(R14)C(O)R14, -NO2, =O, and -CN. In some embodiments, one of R1and R2is selected from hydrogen and C1-6alkyl and the other is selected from C2-6alkynyl optionally substituted with one or more substituents independently selected from halogen, -OR14, -N(R14)2, -NO2, and -CN. In some embodiments, one of R1and R2is selected from hydrogen and C1-6alkyl and the other is selected from C2-6alkynyl. In someembodiments, one of R1and R2is selected from hydrogen and C1-6alkyl and the other is selectedfrom.

[0139] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), or (III), R1and R2are each independently selected from C3-10carbocycle and 3- to 10- membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, - OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, - N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, R1and R2are each independently selected from C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, and -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, - C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, - NO2, =O, =S, =N(R14), and -CN. In some embodiments, R1and R2are each independently selected from C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, and -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, - OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, - N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, R1and R2are each independently selected from C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, - OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, R1and R2are each independently selected from C3-10carbocycle optionally substituted with one or more substituents independently selected from and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, R1and R2are each independently selected from 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, - OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, - N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN.

[0140] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), or (III), one of R1and R2is selected from hydrogen and C1-6alkyl, and the other is selected from C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, - N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, - NO2, =O, =S, =N(R14), -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, one of R1and R2is selected from hydrogen and C1-6alkyl, and the other is selected from C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, and -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, one of R1and R2is selected from hydrogen and C1-6alkyl, and the other is selected from C3-10carbocycle and 3- to 10-membered heterocycle, eachof which is optionally substituted with one or more substituents independently selected from and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, - OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, - N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN.

[0141] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), or (III), one of R1and R2is selected from hydrogen and C1-6alkyl, and the other is C3-10carbocycle optionally substituted with one or more substituents independently selected from and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, - OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, - N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, one of R1and R2is selected from hydrogen and C1-6alkyl, and the other is C3-10carbocycle optionally substituted with C2-6alkynyl, the C2-6alkynyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, one of R1and R2is selected from hydrogen and C1-6alkyl, and the other is C3-10carbocycle optionally substituted with C2-6alkynyl, the C2-6alkynyl optionally substituted with one or more substituents independently selected from: halogen, - OR14, -N(R14)2, -C(O)R14, -C(O)OR14, -NO2, =O, and -CN; and R14is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, one of R1and R2is selected from hydrogen and C1-6alkyl, and the other is C3-10carbocycle substituted with C2-6alkynyl, the C2-6alkynyl optionally substituted with one or more substituents independently selected from halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, and -CN. In someembodiments, one of R1 and R2 is selected from hydrogen and C1-6 alkyl, and the other is.

[0142] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), or (III), one of R1and R2is selected from hydrogen and C1-6alkyl, and the other is selected from hydrogen, -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -C(O)OR14, -OC(O)R14, - N(R14)C(O)OR14, N(R14)C(O)R14, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, and - CN. In some embodiments, one of R1and R2is selected from hydrogen and C1-6alkyl, and theother is selected from hydrogen, -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)OR14, N(R14)C(O)R14, and -CN. In some embodiments, one of R1and R2is selected from hydrogen and C1-6alkyl, and the other is selected from -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, and -CN. In some embodiments, one of R1and R2is selected from hydrogen and C1-6alkyl, and the other is selected from -N(R14)2. In some embodiments, one of R1and R2is selected from hydrogen and C1-6 alkyl, and the other is selected from NMe2,, , , , and. In some embodiments, one of R1 and R2 is selected from NMe2,

[0143] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), or (III), R1and R2may come together to form a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, - N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, - OC(O)N(R15)2, -N(R15)C(O)N(R15)2, -S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, - NO2, =O, =S, =N(R15), and -CN. In some embodiments, R1and R2may come together to form a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C1-6alkyl, C2- 6 alkenyl, and C2-6alkynyl are optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -NO2, =O, and -CN. In some embodiments, R1and R2may come together to form a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, -N(R15)2, - C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, - OC(O)N(R15)2, -N(R15)C(O)N(R15)2, -S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, - NO2, =O, =S, =N(R15), and -CN In some embodiments, R1and R2may come together to form a 3- to 10-membered heterocycle optionally substituted with C2-6alkynyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, -N(R15)2, - C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, - OC(O)N(R15)2, -N(R15)C(O)N(R15)2, -S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN. In some embodiments, R1and R2may come together to form a 3- to 10-membered heterocycle optionally substituted with C2-6alkynyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, - C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, and -CN In some embodiments, R1and R2may come together to form a 3- to 10-membered heterocycle optionally substituted with C2-6alkynyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, and -CN. In some embodiments, R1and R2may come together to form a 3- to 6-membered heterocycle optionally substituted with C2-6alkynyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, and -CN. In some embodiments,is selected from.

[0144] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), or (III), R1and R2may come together to form a 3- to 10-membered saturated heterocycle optionally substituted with one or more substituents independently selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, - N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, - OC(O)N(R15)2, -N(R15)C(O)N(R15)2, -S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, - NO2, =O, =S, =N(R15), and -CN. In some embodiments, R1and R2may come together to form a saturated 3- to 6-membered heterocycle optionally substituted with C2-6alkynyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, - N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, - OC(O)N(R15)2, -N(R15)C(O)N(R15)2, -S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, - NO2, =O, =S, =N(R15), and -CN. In some embodiments, R1and R2may come together to form a saturated 3- to 6-membered heterocycle optionally substituted with C2-6alkynyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)S(O)2R15, - S(O)2N(R15)2, -NO2, =O, and -CN In some embodiments, R1and R2may come together to form a pyrrolidinyl optionally substituted with C2-6alkynyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, - N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, and -CN.

[0145] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), or (III), R1and R2may come together to form a 3- to 10-membered saturated heterocycleoptionally substituted with one or more C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, - C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, - N(R15)C(O)N(R15)2, -S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN. In some embodiments, R1and R2may come together to form a 3- to 10- membered heterocycle optionally substituted C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, and -CN. In some embodiments,is selected from

[0146] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C),.

[0147] In some aspects, the compound or salt of Formula (I) or Formula (III) is represented by the structure of Formula (IV):or a pharmaceutically acceptable salt thereof wherein: Ring A is selected from C3-12carbocycle and 3- to 12-membered heterocycle, each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, - S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; andC3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, - SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; L is represented by -L1- L2-L3-L4-, wherein L1, L2, L3, and L4are each independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, - (R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN; wherein L2, L3, and L4are each optionally absent; wherein no more than two of L1, L2, L3, and L4are selected from (a) and the two selected are not adjacent; R1and R2are each independently selected from (i), (ii), and (iii): (i) hydrogen; (ii) C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; or R1and R2may come together to form a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, - C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, -N(R15)C(O)N(R15)2, - S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, -N(R15)C(O)N(R15)2, - S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN; R3is selected from: hydrogen, halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -C(O)OR16, -NO2, -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, - C(O)OR16, -NO2, and -CN; R11, R12, R13, R14, R15, and R16are each independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted with one more substituents independently selected from halogen, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2, -NO2, =O, -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein each C3-10carbocycle and 3- to 10-membered heterocycle are optionally substituted with one or more substituentsindependently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2, -NO2, =O, and -CN; and C3-6carbocycle and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2, -NO2, =O, and -CN; n is selected from 0, 1, 2, 3, and 4; and m is selected from 0 and 1.

[0148] In some embodiments, m is 1.

[0149] In certain embodiments, the structure of Formula (I), (III), or (IV) is represented by Formula (IV-A):wherein, Ring A, R1, R2, R3, R4, L, and n are each defined as in Formula (I), (III), or (IV).

[0150] In certain embodiments, the structure of Formula (II) is represented by the structure of Formula (IV-B):

[0151] In certain embodiments, the structure of Formula (IV) is represented by the structure of Formula (IV-B):wherein R1, R2, R3, R4, L, Ring A, and n are each as defined as in Formula (I), (III), or (IV).

[0152] In certain embodiments, the structure of Formula (IV) is represented by the structure of Formula (IV-C):

[0153] In certain embodiments, the structure of Formula (IV) is represented by the structure of Formula (IV-C):wherein R1, R2, R3, R4, L, Ring A, and n are each as defined as in Formula (I), (III), or (IV).

[0154] In some embodiments, m is 0. In some embodiments, m is 0 and the structure of Formula (I), (III), or (IV) is represented by Formula (V):

[0155] In some embodiments, m is 0 and the structure of Formula (I), (III), or (IV) is represented by Formula (V):wherein, Ring A, R1, R2, R3, R4, L, and n are each defined as in Formula (I), (III), or (IV).

[0156] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 0.

[0157] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 1.

[0158] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 2.

[0159] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 3.

[0160] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 4.

[0161] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is C3-12 carbocycle. In some embodiments, Ring A is C3-12saturated carbocycle. In some embodiments, Ring A is C3-12unsaturated carbocycle. In some embodiments, Ring A is C6-12 aryl. In some embodiments, Ring A is selected from C3 carbocycle, C4 carbocycle, C5 carbocycle, C6 carbocycle, C7 carbocycle, C8 carbocycle, C9carbocycle, C10carbocycle, C11carbocycle, and C12carbocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, Ring A is selected from C3-4 carbocycle, C3-5 carbocycle, C3-6carbocycle, C3-7 carbocycle, C3-8 carbocycle, C3-9carbocycle, C3-10carbocycle, C3-11carbocycle, and C3-12carbocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, Ring A is selected from C3-8 monocyclic carbocycle and C4-12 bicyclic carbocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, the C3-8monocyclic carbocycle of Ring A is selected from C3-8cycloalkyl and phenyl, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, the C3-8 monocyclic carbocycle of Ring A is phenyl. In some embodiments, the C4-12 bicyclic carbocycleof Ring A is selected from C4-12 fused carbocycle, C4-12 bridged carbocycle, and C4-12 spirocyclic carbocycle, each of which is optionally substituted with R4as defined in Formula (I).

[0162] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is C5-9 carbocycle. In some embodiments, the C5-9 carbocycle of Ring A is selected from C5-7 monocyclic carbocycle and C6-9bicyclic carbocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, the C5-9 carbocycle of Ring A is C5-7 monocyclic carbocycle optionally substituted with R4as defined in Formula (I). In some embodiments, the C5-9 carbocycle of Ring A is C4-7monocyclic carbocycle optionally substituted with R4as defined in Formula (I). In some embodiments, Ring A is selected from Ring A is selected from phenyl and 2,3-dihydro-1H-indenyl, each of which is optionally substituted with R4as defined in Formula (I).

[0163] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is selected from C3-10carbocycle and 3- to 10-membered heterocycle. In some embodiments, Ring A is C6-10 carbocycle. In some embodiments, Ring A is bicyclic C6-10carbocycle. In some embodiments, the bicyclic C6-10 carbocycle of Ring A is selected from C6-10 fused carbocycle, C6-10 bridged carbocycle, and C6-10 spirocyclic carbocycle. In some embodiments, Ring A is C6-10 bridged carbocycle. In some embodiments, Ring A is C6-10spirocyclic carbocycle. In some embodiments, Ring A is C6-10fused carbocycle. In some embodiments, Ring A is indanyl. In some embodiments, Ring A is is dihydroindenyl.

[0164] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is C5-9carbocycle and n is 0. In some embodiments, the C5-9 carbocycle of Ring A is selected from C5-7 monocyclic carbocycle and C6-9 bicyclic carbocycle; and n is 0.

[0165] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is C5-9carbocycle and n is 1. In some embodiments, the C5-9 carbocycle of Ring A is selected from C5-7 monocyclic carbocycle and C6-9bicyclic carbocycle; and n is 1.

[0166] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is C5-9 carbocycle and n is 2. In some embodiments, the C5-9 carbocycle of Ring A is selected from C5-7 monocyclic carbocycle and C6-9bicyclic carbocycle; and n is 2.

[0167] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is C5-9 carbocycle and nis 3. In some embodiments, the C5-9 carbocycle of Ring A is selected from C5-7 monocyclic carbocycle and C6-9bicyclic carbocycle; and n is 3.

[0168] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is selected from phenyl and 2,3-dihydro-1H-indenyl; n is 0. In some embodiments, Ring A is phenyl and n is 0. In some embodiments, Ring A is 2,3-dihydro-1H-indenyl and n is 0. In some embodiments,.

[0169] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), R4is selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, - SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN.

[0170] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), R4is selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, - S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; and 5- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, - C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, - S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN.

[0171] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), R4is selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, - S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, - N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN.

[0172] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), R4is selected from halogen, - OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, - S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN. In some embodiments, R4is selected from halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -NO2, =O, =S,=N(R11), and -CN. In some embodiments, R4is selected from halogen, -OR11, -N(R11)2, - C(O)R11, -NO2, and -CN. In some embodiments, R4 is selected from ethyl,, ,and

[0173] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), R4is selected from 3- to 10- membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, - S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN. In some embodiments, R4is selected from 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, - C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN. In some embodiments, R4is selected from 5- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, - OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, - S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN. In some embodiments, R4is selected from 5- to 6-membered heteroaryl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, - NO2, =O, =S, =N(R11), and -CN. In some embodiments, R4is pyrazolyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -NO2, =O, =S, =N(R11), and -CN. In some embodiments, R4is selected from

[0174] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 1 and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, - S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, n is 1; and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)N(R11)2, -N(R11)C(O)R11, - N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. Insome embodiments, n is 1; and R4is independently selected from halogen, -OR11, -N(R11)2, - C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0175] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 1; R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, - S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, n is 1; R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)R11, -C(O)OR11, - OC(O)R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, n is 1; R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0176] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is C3-12 carbocycle; n is 1; and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, - C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is C3-12carbocycle; n is 1; and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)R11, -C(O)OR11, - OC(O)R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is C3-12carbocycle; n is 1; and R4is independently selected from halogen, -OR11, -N(R11)2, - C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0177] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is C3-7 carbocycle; n is 1; and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is C3-7carbocycle; n is 1; and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)R11, -C(O)OR11, - OC(O)R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is C3-7 carbocycle; n is 1; and R4is independently selected from halogen, -OR11, -N(R11)2, - C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0178] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is phenyl; n is 1; and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, - N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is phenyl; n is 1; and R4is independently selected from halogen, - OR11, -N(R11)2, -C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is phenyl; n is 1; and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)N(R11)2, -N(R11)C(O)R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0179] In some embodiments, for the compound or salt of Formula (I), (III), (IV), (IV-A), (IV-.

[0180] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 1 and R4is independently selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, - C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, =O, =S, =N(R11), and -CN. In some embodiments, n is 1 and R4is independently selected from C1-6alkyl and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, - C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, n is 1 and R4is independently selected from C1-6alkyl and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selectedfrom: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, and -CN.

[0181] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 1 and R4is independently selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, - C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, =O, =S, =N(R11), and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, n is 1 and R4is independently selected from C1-6alkyl and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, - S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, n is 1 and R4is independently selected from C1-6alkyl and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0182] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is C3-12 carbocycle; n is 1; and R4is independently selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, - OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, - S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN. In some embodiments, Ring A is C3-12carbocycle; n is 1; and R4is independently selected from C1-6alkyl and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, - OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is C3-12 carbocycle; n is 1; and R4is independently selected from C1-6alkyl and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0183] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is C3-7carbocycle; n is 1; and R4is independently selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, - OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, - S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN. In some embodiments, Ring A is C3-7 carbocycle; n is 1; and R4is independently selected from C1-6alkyl and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, - OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is C3-7carbocycle; n is 1; and R4is independently selected from C1-6alkyl and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0184] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is phenyl; n is 1; and R4is independently selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, - OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, - S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN. In some embodiments, Ring A is phenyl; n is 1; and R4is independently selected from C1-6alkyl and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, and -CN. In some embodiments, Ring A is phenyl; n is 1; and R4is independently selected from C1-6alkyl and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0185] In some embodiments, for the compound or salt of Formula (I), (III), (IV), (IV-A), (IV-

[0186] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 1 and R4is independently selected from C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, and -CN. In some embodiments, n is 1 and R4is independently selected from 3- to 6- membered heteroaryl optionally substituted with one or more substituents independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, - S(O)2N(R11)2, -NO2, and -CN.

[0187] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 1 and R4is independently selected from C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, and -CN; and R11is selected from halogen, C1-6alkyl and C1-6haloalkyl. In some embodiments, n is 1 and R4is independently selected from 3- to 6-membered heteroaryl optionally substituted with one or more substituents independently selected from halogen, - OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from halogen, C1-6alkyl and C1-6haloalkyl.

[0188] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is C3-12carbocycle; n is 1; and R4is independently selected from C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, - OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is C3-12 carbocycle; n is 1; and R4is independently selected from 3- to 6-membered heteroaryl optionally substituted with one or more substituents independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0189] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is C3-7carbocycle; n is 1; and R4is independently selected from C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, - OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is C3-7 carbocycle; n is 1; and R4is independently selected from 3- to 6-membered heteroaryl optionally substituted with one or more substituents independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0190] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is phenyl; n is 1; and R4is independently selected from C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, - OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is phenyl; n is 1; and R4is independently selected from 3- to 6-membered heteroaryl optionally substituted with one or more substituents independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments,

[0191] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 2 and each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, - C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, - C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN. In some embodiments, n is 2 and each R4is independently selected at each occurrence from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)R11, -N(R11)C(O)OR11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, n is 2 and each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, and -CN. In some embodiments, n is 2 and each R4is independently selected at each occurrence from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)R11, -N(R11)C(O)OR11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, n is 2 and each R4is independently selected at each occurrence from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, - OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN. In some embodiments, n is 2 and each R4is independently selected at each occurrence from: C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0192] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 2 and each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, - C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, n is 2 and each R4is independently selected at each occurrence from: halogen, - OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, n is 2 and each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, - S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, n is 2 and each R4is independently selected at each occurrence from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, =O, =S, =N(R11), and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, n is 2 and each R4is independently selected at each occurrence from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, n is 2 and each R4is independently selected at each occurrence from: C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0193] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is a C3-12carbocycle; n is 2; and each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, and -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, =O, =S, =N(R11), and -CN. In some embodiments, Ring A is a C3-12 carbocycle; n is 2; andeach R4is independently selected at each occurrence from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is a C3-12 carbocycle; n is 2; and each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, - N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is a C3-12carbocycle; n is 2; and each R4is independently selected at each occurrence from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)R11, -N(R11)C(O)OR11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is a C3-12 carbocycle; n is 2; and each R4is independently selected at each occurrence from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, - N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN. In some embodiments, Ring A is a C3-12 carbocycle; n is 2; and each R4is independently selected at each occurrence from: C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0194] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is a C3-7carbocycle; n is 2; and each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, and -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, =O, =S, =N(R11), and -CN. In some embodiments, Ring A is a C3-7carbocycle; n is 2; and each R4is independently selected at each occurrence from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is a C3-7 carbocycle; n is 2; and each R4is independently selectedat each occurrence from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, - N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is a C3-7 carbocycle; n is 2; and each R4is independently selected at each occurrence from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)R11, -N(R11)C(O)OR11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is a C3-7carbocycle; n is 2; and each R4is independently selected at each occurrence from: C1-6alkyl, C2- 6 alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, - N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN. In some embodiments, Ring A is a C3-7carbocycle; n is 2; and each R4is independently selected at each occurrence from: C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0195] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II- C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is phenyl; n is 2; and each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, -N(R11)2, - C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, and -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, =O, =S, =N(R11), and -CN. In some embodiments, Ring A is phenyl; n is 2; and each R4is independently selected at each occurrence from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is phenyl; n is 2; and each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, - S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is phenyl; n is 2; and each R4is independently selected at each occurrence from: halogen, -OR11, - N(R11)2, -C(O)R11, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2,and -CN. In some embodiments, Ring A is phenyl; n is 2; and each R4is independently selected at each occurrence from: C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, =O, =S, =N(R11), and -CN. In some embodiments, Ring A is phenyl; n is 2; and each R4is independently selected at each occurrence from: C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0196] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 2 and each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, - C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, - N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN. In some embodiments, n is 2 and each R4is independently selected at each occurrence from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)R11, -N(R11)C(O)OR11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, n is 2 and each R4is independently selected at each occurrence from: halogen, - OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, n is 2 and each R4is independently selected at each occurrence from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and 5- to 6- membered heteroaryl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)R11, -N(R11)S(O)2R11, - S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is phenyl; n is 2 and each R4isindependently selected at each occurrence from: halogen, -OR11, -N(R11)2, and -CN; and 3- to 6- membered heterocycle. In some embodiments,.

[0197] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), ,

[0198] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C),

[0199] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 3 and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, - S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, n is 3 and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, - N(R11)C(O)R11, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0200] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 3 and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, - S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, n is 3 and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, - N(R11)C(O)R11, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0201] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 3 and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, - S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, n is 3 and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0202] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 3 and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, - S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, n is 3 and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0203] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is a C3-12 carbocycle; n is 3; and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, - C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is a C3-12 carbocycle; n is 3; and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0204] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is a C3-12carbocycle; n is 3; and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, - C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is a C3-12 carbocycle; n is 3; and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0205] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is a C3-7 carbocycle; n is3; and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, - C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is a C3-7 carbocycle; n is 3; and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0206] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is phenyl; n is 3; and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, - N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is phenyl; n is 3; and R4is independently selected from halogen, - OR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0207] In some embodiments, for the compound or salt of Formula (I), (III), (IV), (IV-A), (IV- B), (IV-C), or (V),

[0208] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is 3- to 12-membered heterocycle. In some embodiments, Ring A is 3- to 12-membered heterocycle comprising at least one heteroatom selected from oxygen, nitrogen, and sulfur. In some embodiments, Ring A is 3- to 12-membered unsaturated heterocycle. In some embodiments, Ring A is 3- to 12- membered heteroaryl. In some embodiments, Ring A is selected from 3-membered heterocycle, 4-membered heterocycle, 5-membered heterocycle, 6-membered heterocycle, 7-membered heterocycle, 8-membered heterocycle, 9-membered heterocycle, 10-membered heterocycle, and 11-membered heterocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, Ring A is selected from 3- to 4-membered heterocycle, 3- to 5- membered heterocycle, 3- to 6-membered heterocycle, 3- to 7-membered heterocycle, 3- to 8- membered heterocycle, 3- to 9-membered heterocycle, 3- to 10-membered heterocycle, 3- to 11- membered heterocycle, and 3- to 12-membered heterocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, Ring A is selected from 3- to 8-membered monocyclic heterocycle and 4- to 12-membered bicyclic heterocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, Ring Ais selected from 3- to 8-membered monocyclic heterocycle and 8- to 12-membered bicyclic heterocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, Ring A is selected from 3- to 8-membered monocyclic heterocycle and 8- to 12- membered bicyclic heterocycle. In some embodiments, the 4- to 12-membered bicyclic heterocycle is selected from 4- to 12-membered fused heterocycle, 4- to 12-membered bridged heterocycle, and 4- to 12-membered spirocyclic heterocycle, each of which is optionally substituted with R4as defined in Formula (I).

[0209] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is 3- to 12-membered heterocycle. In some embodiments, the 3- to 12-membered heterocycle is selected from 3- to 8- membered monocyclic heterocycle and 8- to 12-membered bicyclic heterocycle, each of which is optionally substituted with R4as defined in Formula (I). In some embodiments, the 3- to 12- membered heterocycle is 3- to 8-membered monocyclic heterocycle, optionally substituted with R4as defined in Formula (I). In some embodiments, the 3- to 12-membered heterocycle is 8- to 12-membered bicyclic heterocycle, optionally substituted with R4as defined in Formula (I). In some embodiments, Ring A is selected from pyridyl, isoindolinyl, dihydrobenzofuranyl, indazolyl, benzo[d]thiazolyl, and isoquinolinyl, each of which is optionally substituted with R4as defined in Formula (I).

[0210] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is a 3- to 12-membered heterocycle and n is 0. In some embodiments, the 3- to 12-membered of Ring A is selected from 3- to 8-membered monocyclic heterocycle and 8- to 12-membered bicyclic heterocycle; and n is 0.

[0211] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is a 3- to 12-membered heterocycle and n is 1. In some embodiments, the 3- to 12-membered of Ring A is selected from 3- to 8-membered monocyclic heterocycle and 8- to 12-membered bicyclic heterocycle; and n is 1.

[0212] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is a 3- to 12-membered heterocycle and n is 2. In some embodiments, the 3- to 12-membered of Ring A is selected from 3- to 8-membered monocyclic heterocycle and 8- to 12-membered bicyclic heterocycle; and n is 2.

[0213] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is a 3- to 12-memberedheterocycle and n is 3. In some embodiments, the 3- to 12-membered of Ring A is selected from 3- to 8-membered monocyclic heterocycle and 8- to 12-membered bicyclic heterocycle; and n is 3.

[0214] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is selected from pyridyl, isoindolinyl, dihydrobenzofuranyl, indazolyl, benzo[d]thiazolyl, and isoquinolinyl.

[0215] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is selected from pyridyl, isoindolinyl, dihydrobenzofuranyl, indazolyl, benzo[d]thiazolyl, and isoquinolinyl and n is 0. In some embodiments, n is 0.

[0216] In some embodiments, for the compound or salt of Formula (I), (III), (IV), (IV-A), (IV-.

[0217] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is selected from pyridyl, isoindolinyl, dihydrobenzofuranyl, indazolyl, benzo[d]thiazolyl, and isoquinolinyl and n is 1.

[0218] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 1 and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, - S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, -CN, and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, n is 1 and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0219] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 1 and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, - S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN. In some embodiments, n is 1 and R4 is independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0220] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is 1 and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, - S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, n is 1 and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0221] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is a 3- to 12-membered heterocycle; n is 1; and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, - C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, - S(O)2N(R11)2, -NO2, and -CN. In some embodiments, Ring A is a 3- to 12-membered heterocycle; n is 1; and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0222] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is a 3- to 12-membered heterocycle; n is 1; and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, - C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, and -CN. In some embodiments, Ring A is a 3- to 12-membered heterocycle; n is 1; and R4 is independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0223] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is an 8- to 12-membered bicyclic heterocycle; n is 1; and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, and -CN. In some embodiments, Ring A is an 8- to 12-membered bicyclic heterocycle; n is 1; and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0224] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is a 3- to 8-membered monocyclic heterocycle; n is 1; and R4is independently selected from halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, and -CN. In some embodiments, Ring A is a 3- to 8-membered monocyclic heterocycle; n is 1; and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

[0225] In some embodiments, for the compound or salt of Formula (I), (III), (IV), (IV-A), (IV-

[0226] In some embodiments, for the compound or salt of Formula (I), (II), (III), (IV), (IV-A),

[0227] In some embodiments, for the compound or salt of Formula (I), (III), (IV), (IV-A), (IV-

[0228] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), any of L1, L2, L3, or L4is independently selected from C3-12carbocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from C3-12 unsaturated carbocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from C3-12 arylene. In some embodiments, any of L1, L2, L3, or L4is independently selected from C3carbocyclene, C4carbocyclene, C5carbocyclene, C6carbocyclene, C7 carbocyclene, C8 carbocyclene, C9 carbocyclene, C10 carbocyclene, and C11 carbocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from C3-4 carbocyclene, C3-5carbocyclene, C3-6carbocyclene, C3-7carbocyclene, C3-8carbocyclene, C3-9carbocyclene, C3-10carbocyclene, C3-11carbocyclene, and C3-12carbocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected C3-8 monocyclic carbocyclene and C8-12 bicyclic carbocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from C3-8monocyclic carbocyclene and C4-12bicyclic carbocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from C3-8 monocycliccarbocyclene and C8-12 bicyclic carbocyclene. In some embodiments, the C4-12 carbocyclene is selected from C4-12carbocyclene, C4-12bridged carbocyclene, and C4-12spirocyclic carbocyclene.

[0229] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), any of L1, L2, L3, or L4is independently selected from 3- to 12-membered heterocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from 3- to 12-membered heterocyclene comprising at least one heteroatom selected from oxygen, nitrogen, and sulfur. In some embodiments, any of L1, L2, L3, or L4is independently selected from 3- to 12-membered unsaturated heterocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from 3- to 12-membered heteroarylene. In some embodiments, any of L1, L2, L3, or L4is independently selected from 3- membered heterocyclene, 4-membered heterocyclene, 5-membered heterocyclene, 6-membered heterocyclene, 7-membered heterocyclene, 8-membered heterocyclene, 9-membered heterocyclene, 10-membered heterocyclene, and 11-membered heterocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from 3- to 4-membered heterocyclene, 3- to 5-membered heterocyclene, 3- to 6-membered heterocyclene, 3- to 7- membered heterocyclene, 3- to 8-membered heterocyclene, 3- to 9-membered heterocyclene, 3- to 10-membered heterocyclene, 3- to 11-membered heterocyclene, and 3- to 12-membered heterocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from 3- to 8-membered monocyclic heterocyclene and 4- to 12-membered bicyclic heterocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from 3- to 8-membered monocyclic heterocyclene and 8- to 12-membered bicyclic heterocyclene. In some embodiments, any of L1, L2, L3, or L4is independently selected from 3- to 8-membered monocyclic heterocyclene and 8- to 12-membered bicyclic heterocyclene. In some embodiments, the 4- to 12-membered bicyclic heterocyclene is selected from 4- to 12-membered fused heterocyclene, 4- to 12-membered bridged heterocyclene, and 4- to 12-membered spirocyclic heterocyclene.

[0230] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), each of L2, L3and L4are absent and L1is selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, - N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or moresubstituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN. In some embodiments, each of L2, L3and L4are absent and L1is selected from (a) and (b): (a) -O-, - N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, - N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, - N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, and C2-6alkynylene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN. In some embodiments, each of L2, L3and L4are absent and L1is selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, - N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, - N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN.

[0231] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), each of L2, L3and L4are absent and L1is selected from (a) and (b): (a) -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and - CN. In some embodiments, each of L2, L3and L4are absent and L1is selected from (a) and (b):(a) -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and - (R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN. In some embodiments, each of L2, L3and L4are absent and L1is selected from (a) and (b): (a) - N(R12)C(O)-, -N(R12)C(O)C(O)N(R12)-, and -(R12)NC(O)N(R12)-; and (b) C1-6alkylene which is optionally substituted with one or more substituents independently selected from halogen, - OR13, -SR13, =O, =S, -CN. In some embodiments, each of L2, L3and L4are absent and L1isselected from -N(R12)C(O)-, -N(R12)C(O)C(O)N(R12)-, and -(R12)NC(O)N(R12)-; and R12is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0232] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), each of L2, L3and L4are absent and L1is selected from (a) and (b): (a) -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)O-, - N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, - N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN. In some embodiments, each of L2, L3and L4are absent and L1is selected from (a) and (b):(a) -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, - N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN. In some embodiments, each of L2, L3and L4are absent and L1is selected from (a) and (b): (a) -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)C(O)N(R12)-, and - (R12)NC(O)N(R12)-; and (b) C1-6alkylene which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN. In some embodiments, each of L2, L3and L4are absent and L1is selected from -N(R12)-, -N(R12)C(O)-, - N(R12)C(O)C(O)N(R12)-, and -(R12)NC(O)N(R12)-; and R12is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0233] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), L1is selected from -N(R12)C(O)- , -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and R12is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, L1is selected from -N(R12)C(O)-, -N(R12)C(O)C(O)N(R12)-, and - (R12)NC(O)N(R12)-; and R12is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0234] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), L1is selected from -N(R12)-, - N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and R12is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.In some embodiments, L1is selected from -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)C(O)N(R12)-, and -(R12)NC(O)N(R12)-; and R12is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0235] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), L is selected from:,some embodiments, L is selected from: and . In some embodiments, L is. In some embodiments, L is . In some embodiments, L is.

[0236] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C),. , .

[0237] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, - S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and - (R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN,C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN. In some embodiments, each of L3and L4are absent and each of L1and L2is selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, - N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, and C2-6alkynylene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, - OR13, -SR13, =O, =S, and -CN. In some embodiments, each of L3and L4are absent and each of L1and L2is selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, - N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, - OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN.

[0238] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, -N(R12)C(O)-, - N(R12)C(O)O-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, and -(R12)NC(O)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN.In some embodiments, each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, -N(R12)C(O)-, and - N(R12)C(O)O-; and (b) C1-6alkylene and C2-6alkenylene, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN. In some embodiments, each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, -N(R12)C(O)-, and -N(R12)C(O)O-; and (b) C1-6alkylene and C2-6alkenylene, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at eachoccurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, L is selected from:, , , , , ,, , , , , and. In some embodiments, L is selected from, a d . In some embodiments, L is selected from, and . In some embodiments, L is selected from, , and . In some embodiments, L is.

[0239] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, - S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and - (R12)NC(O)N(R12)N(R12)-; and (b) C3-10carbocyclene and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -N(R12)-, -N(R12)C(O)-, - N(R12)C(O)O-, and -(R12)NC(O)N(R12)-; and (b) C3-10carbocyclene and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituentsindependently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0240] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, - S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and - (R12)NC(O)N(R12)N(R12)-; and (b) C3-10carbocyclene optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)O-, and -(R12)NC(O)N(R12)-; and (b) C3-10carbocyclene optionally substituted with one or more substituents independently selected from halogen, - OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, - OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)O-, and - (R12)NC(O)N(R12)-; and (b) C3-6saturated carbocyclene optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments,L is selected from.

[0241] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, - S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and - (R12)NC(O)N(R12)N(R12)-; and (b) 3- to 10-membered heterocyclene optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)O-, and -(R12)NC(O)N(R12)-; and (b) 3- to 10-membered heterocyclene optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0242] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -N(R12)-, -N(R12)C(O)-, - N(R12)C(O)O-, and -(R12)NC(O)N(R12)-; and (b) 3- to 6-membered saturated heterocyclene and 3- to 6-membered unsaturated heterocyclene optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, L is selected

[0243] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -N(R12)-, -N(R12)C(O)-, - N(R12)C(O)O-, and -(R12)NC(O)N(R12)-; and (b) 5- to 6-membered heteroarylene and 6- to 10- membered bicyclic heterocyclene optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, L is selected, , , ,, , . In some embodiments, L is selected from, , , .

[0244] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), L is selected from:

[0245] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C),, , ,

[0246] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), L is selected from:

[0247] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), L4is absent and each of L1, L2, and L3are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, - S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and - (R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN. In some embodiments, L4is absent and each of L1, L2, and L3are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, - N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, and C2-6alkynylene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN. In some embodiments, L4is absent and each of L1, L2, and L3are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, - N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, - OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN.

[0248] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), L4is absent and each of L1, L2, and L3are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -N(R12)C(O)-, and - N(R12)C(O)O-; and (b) C1-6alkylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10- membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, halogen, -OR13, -CN, C1-6alkyl; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, L4is absent and each of L1, L2, and L3are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -N(R12)C(O)-, and -N(R12)C(O)O-; and (b) C1-6alkylene, C2-6alkynylene, C3-6carbocyclene, and 3- to 6-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, - OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, halogen, -OR13, -CN, C1-6alkyl; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0249] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), L is selected from:,

[0250] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), each of L1, L2, L3and L4are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, - N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN.

[0251] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), each of L1, L2, L3and L4are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, - N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In someembodiments, each of L1, L2, L3and L4are independently selected from (a) and (b): (a) -O-, - N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, - N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, - N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, and C2-6alkynylene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN. In some embodiments, each of L1, L2, L3and L4are independently selected from (a) and (b): (a) - O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, - N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, - N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and -(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN. In some embodiments, L is selected from:, and.

[0252] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), L is selected from:,

[0253] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), one of R1or R2is hydrogen.

[0254] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), one of R1or R2is selected from hydrogen and the other of R1or R2is selected from C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S,=N(R14), and -CN; and C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, - OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, - N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, one of R1or R2is selected from hydrogen and the other of R1or R2is selected from C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and C3-6carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, - OR14, -N(R14)2, -C(O)R14, -NO2, -CN; and R14is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, one of R1or R2is selected from hydrogen and the other of R1or R2is selected from C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, and - CN; and C3-6carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, and -CN; and R14is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, one of R1or R2is selected from hydrogenand the other of R1 or R2 is selected from, , , , , ,, . In some embodiments, one of R1or R2is selected fromhydrogen and the other of R1 or R2 is selected from, , , , ,some embodiments, one of R1or R2is selected from hydrogen and the other of R1or R2is.

[0255] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), one of R1or R2is selected from hydrogen and the other of R1or R2is selected from C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, - OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, - N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, one of R1or R2is selected from hydrogen and theother of R1or R2is selected from C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, -CN. In some embodiments, one of R1or R2is selected from hydrogen and the other of R1or R2is selected from C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, and -CN; and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, and - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, and -CN; and R14is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, one of R1 or R2is selected from hydrogen and the other of R1or R2is selected from,

[0256] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (III), (II-a),

[0257] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), one of R1or R2is selected from hydrogen and the other of R1or R2is selected from C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, - S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, - OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, - N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, one of R1or R2is selected from hydrogen and the other of R1or R2is selected from C3-6carbocycle and 3- to 6- membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, =O, =S, =N(R14), and - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, =O, =S, =N(R14), and -CN. In some embodiments, one of R1or R2is selected from hydrogen and the other of R1or R2is selected from C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, =O, =S, =N(R14), and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, =O, =S, =N(R14), and -CN; and R14is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0258] In some embodiments, one of R1or R2is selected from hydrogen and the other of R1or R2is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and tetrahydropyranyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, =O, =S, =N(R14), and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, - OR14, -N(R14)2, -C(O)R14, -NO2, =O, =S, =N(R14), and -CN; and R14is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, one of R1or R2 is selected from hydrogen and the other of R1 or R2 is selected from:, ,some embodiments,one of R1or R2is selected from hydrogen and the other of R1or R2is selected from:some embodiments, one of R1or R2is selected from hydrogen and the other of R1or R2is. In some embodiments, one of R1 or R2 is selected from hydrogen and the other of

[0259] In some embodiments, one of R1or R2is selected from hydrogen and the other of R1or R2is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentyl, oxetanyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, pyridyl, and phenyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, - OR14, -N(R14)2, -C(O)R14, -NO2, =O, =S, =N(R14), and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR14, -N(R14)2, -C(O)R14, - NO2, =O, =S, =N(R14), and -CN; and R14is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl. In some embodiments, one of R1or R2is selected fromhydrogen and the other of R1 or R2 is selected from:, , , , ,, , , , , , , , .In some embodiments, one 1 2of R or R is selected from hydrogen andthe other of R1 or R2 is selected from:, , , , ,, ,

[0260] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), one of R1or R2is selected from hydrogen and the other of R1 or R2 is selected from, , , , ,, , and .

[0261] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), one of R1or R2is selected from hydrogen and the other of R1 or R2 is selected from

[0262] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), one of R1or R2is selected fromhydrogen and the other of R1 or R2 is selected from, , , , ,

[0263] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), R1and R2may come together to form a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, - N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, - N(R15)C(O)N(R15)2, -S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, - N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, - N(R15)C(O)N(R15)2, -S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN. In some embodiments, R1and R2may come together to form a 3- to 6- membered saturated heterocycle optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, =O, =S, =N(R15), -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, =O, =S, =N(R15), and -CN. In some embodiments, R1and R2may come together to form a 3- to 6-membered saturated heterocycle optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, =O, =S, =N(R15), -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, =O, =S, =N(R15), and -CN; and R15is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6 haloalkyl. In some embodiments,is selected from

[0264] In some embodiments, R1and R2may come together to form a 3- to 8-membered saturated heterocycle optionally substituted with one or more substituents independentlyselected from halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, =O, =S, =N(R15), -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, - OR15, -N(R15)2, -C(O)R15, -NO2, =O, =S, =N(R15), and -CN. In some embodiments, R1and R2may come together to form a 3- to 8-membered saturated heterocycle optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, =O, =S, =N(R15), -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, =O, =S, =N(R15), and - CN; and R15is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6.

[0265] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), R11, R12, R13, R14, R15, and R16are each independently selected at each occurrence from hydrogen; C1-6alkyl optionally substituted with one more substituents independently selected from halogen, -O-C1-6alkyl, -O- C1-6haloalkyl, -NH2, -NO2, =O, -CN, C3-6carbocycle, and 3- to 6-membered heterocycle; and C3-6carbocycle and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,- NO2, =O, and -CN. In some embodiments, R11, R12, R13, R14, R15, and R16are each independently selected at each occurrence from hydrogen, C1-6alkyl, C1-6haloalkyl, C1-6alkyl- O-C1-6alkyl, C1-6alkyl-O-C1-6haloalkyl, C1-6alkyl-(C3-6carbocycle) and C1-6alkyl-(3- to 6- membered heterocycle), C3-6carbocycle, 3- to 6-membered heterocycle. In some embodiments, R11, R12, R13, R14, R15, and R16are each independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

[0266] In some aspects, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II- D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), Ring A is selected from C3-6carbocycle and 3- to 6-membered heterocycle.

[0267] In some aspects, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II- D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), n is selected from 0, 1, and 2.

[0268] In some aspects, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II- D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), R4is selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, - S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN.

[0269] In some aspects, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II- D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), L is represented by -L1- L2-L3-L4-, wherein L1, L2, L3, and L4are each independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and - (R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10- membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN.

[0270] In some aspects, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II- D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), R3is selected from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -C(O)OR16, -NO2, and -CN.

[0271] In some aspects, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II- D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), R1or R2is hydrogen.

[0272] In some aspects, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II- D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), R1or R2is selected from:C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and C3-6carbocycle optionally substituted with one or more substituents independently selected from halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), -CN, C1-6alkyl, and C1-6haloalkyl.

[0273] In some aspects, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II- D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), one of R1and R2is selected from hydrogen and the other of R1or R2is selected from: C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and C3-6carbocycle optionally substituted with one or more substituents independently selected from halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), -CN, C1-6alkyl, and C1-6haloalkyl.

[0274] In some embodiments, the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), is selected from a compound in Table 1.

[0275] Table 1. Selected CDK2 modulators. * Denotes a stereocenter with an undetermined absolute stereochemistry of a single isomer.126127128129130131132133134135136137138139140141

[0276] In some embodiments, for the compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), or (II-F), is selected from a compound in Table 1A.

[0277] Table 1A. Selected CDK2 Prodrug Compounds. * Denotes a stereocenter with an undetermined absolute stereochemistry of a single isomer.142143144145

[0278] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

[0279] Chemical entities having carbon-carbon double bonds or carbon-nitrogen double bonds may exist in Z- or E- form (or cis- or trans- form). Furthermore, some chemical entities may exist in various tautomeric forms. Unless otherwise specified, compounds or salts of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), are intended to include all Z-, E- and tautomeric forms as well.

[0280] “Isomers” are different compounds that have the same molecular formula. “Stereoisomers” are isomers that differ only in the way the atoms are arranged in space. “Enantiomers” are a pair of stereoisomers that are non-superimposable mirror images of each other. A 1:1 mixture of a pair of enantiomers is a “racemic” mixture. The term “(±)” is used to designate a racemic mixture where appropriate. “Diastereoisomers” or “diastereomers” are stereoisomers that have at least two asymmetric atoms but are not mirror images of each other. The absolute stereochemistry is specified according to the Cahn-Ingold-Prelog R-S system. When a compound is a pure enantiomer, the stereochemistry at each chiral carbon can be specified by either R or S. Resolved compounds whose absolute configuration is unknown can be designated (+) or (-) depending on the direction (dextro- or levorotatory) in which they rotate plane polarized light at the wavelength of the sodium D line. Certain compounds described herein contain one or more asymmetric centers and can thus give rise to enantiomers, diastereomers, and other stereoisomeric forms, the asymmetric centers of which can be defined, in terms of absolute stereochemistry, as (R)- or (S)-. The present chemical entities, pharmaceutical compositions and methods are meant to include all such possible stereoisomers, including racemic mixtures, optically pure forms, mixtures of diastereomers and intermediate mixtures. Optically active (R)- and (S)-isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. The optical activity of a compound can be analyzed via any suitable method, including but not limited to chiral chromatography and polarimetry, and the degree of predominance of one stereoisomer over the other isomer can be determined.

[0281] The compounds or salts for Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), may in some cases exist as diastereomers, enantiomers, or other stereoisomeric forms. The compounds presented herein include all diastereomeric, enantiomeric, and epimeric forms as well as the racemates, mixtures of diastereomers, and other mixtures thereof, to the extent they can be made by one of ordinary skill in the art by routine experimentation. Separation of stereoisomers may be performed by chromatography or by forming diastereomers and separating by recrystallization, or chromatography, or any combination thereof. (Jean Jacques, Andre Collet, Samuel H. Wilen, “Enantiomers, Racemates and Resolutions”, John Wiley And Sons, Inc., 1981, herein incorporated by reference for this disclosure). Stereoisomers may also be obtained by stereoselective synthesis. Furthermore, a mixture of two enantiomers enriched in one of the two can be purified to provide further optically enriched form of the major enantiomer by recrystallization and / or trituration.

[0282] In certain embodiments, compounds or salts for Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), may comprise two or more enantiomers or diastereomers of a compound wherein a single enantiomer or diastereomer accounts for at least about 70% by weight, at least about 80% by weight, at least about 90% by weight, at least about 98% by weight, or at least about 99% by weight or more of the total weight of all stereoisomers. Methods of producing substantially pure enantiomers are well known to those of skill in the art. For example, a single stereoisomer, e.g., an enantiomer, substantially free of its stereoisomer may be obtained by resolution of the racemic mixture using a method such as formation of diastereomers using optically active resolving agents (Stereochemistry of Carbon Compounds, (1962) by E. L. Eliel, McGraw Hill; Lochmuller (1975) J. Chromatogr., 113(3): 283-302). Racemic mixtures of chiral compounds can be separated and isolated by any suitable method, including, but not limited to: (1) formation of ionic, diastereomeric salts with chiral compounds and separation by fractional crystallization or other methods, (2) formation of diastereomeric compounds with chiral derivatizing reagents, separation of the diastereomers, and conversion to the pure stereoisomers, and (3) separation of the substantially pure or enriched stereoisomers directly under chiral conditions. Another approach for separation of the enantiomers is to use a Diacel chiral column and elution using an organic mobile phase such as done by Chiral Technologies (www.chiraltech.com) on a fee for service basis.

[0283] A "tautomer" refers to a molecule wherein a proton shift from one atom of a molecule to another atom of the same molecule is possible. In certain embodiments, the compounds or salts for Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), exist as tautomers. In circumstances where tautomerization is possible, a chemical equilibrium of the tautomers may exist. The exact ratio of the tautomers depends on several factors, including physical state, temperature, solvent, and pH. Some non–limiting examples of tautomeric equilibrium include:.

[0284] The compounds disclosed herein, in some embodiments, are used in different enriched isotopic forms, e.g., enriched in the content of2H,3H,11C,13C and / or14C. In one particular embodiment, the compound is deuterated in at least one position. Such deuterated forms can be made by the procedure described in U.S. Patent Nos.5,846,514 and 6,334,997. As described in U.S. Patent Nos.5,846,514 and 6,334,997, deuteration can improve the metabolic stability and or efficacy, thus increasing the duration of action of drugs.

[0285] In certain embodiments, the compounds disclosed herein have some or all of the1H atoms replaced with2H atoms. The methods of synthesis for deuterium-containing compounds are known in the art and include, by way of non-limiting example only, the following synthetic methods.

[0286] Deuterium substituted compounds are synthesized using various methods such as described in: Dean, Dennis C.; Editor. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [In: Curr., Pharm. Des., 2000;6(10)] 2000, 110 pp; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0287] Deuterated starting materials are readily available and are subjected to the synthetic methods described herein to provide for the synthesis of deuterium-containing compounds. Large numbers of deuterium-containing reagents and building blocks are available commercially from chemical vendors, such as Aldrich Chemical Co.

[0288] Unless otherwise stated, compounds described herein are intended 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, or the replacement of a carbon by13C- or14C-enriched carbon are within the scope of the present disclosure.

[0289] The compounds of the present disclosure optionally contain unnatural proportions of atomic isotopes at one or more atoms that constitute such compounds. For example, the compounds may be labeled with isotopes, such as for example, deuterium (2H), tritium (3H), iodine-125 (125I) or carbon-14 (14C). Isotopic substitution with2H,11C,13C,14C,15C,12N,13N,15N,16N,16O,17O,14F,15F,16F,17F,18F,33S,34S,35S,36S,35Cl,37Cl,79Br,81Br, and125I are all contemplated. All isotopic variations of the compounds of the present invention, whether radioactive or not, are encompassed within the scope of the present invention.

[0290] Included in the present disclosure are salts, particularly pharmaceutically acceptable salts, of the compounds of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V). The compounds of the present disclosure may possess a sufficiently acidic, a sufficiently basic, or both functional groups, can react with any of a number of inorganic bases, and inorganic and organic acids, to form a salt. Alternatively, compounds that are inherently charged, such as those with a quaternary nitrogen, can form a salt with an appropriate counterion, e.g., a halide such as bromide, chloride, or fluoride, particularly bromide.

[0291] The methods and compositions of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), include the use of amorphous forms as well as crystalline forms (also known as polymorphs). The compounds described herein may be in the form of pharmaceutically acceptable salts. As well, in some embodiments, active metabolites of these compounds having the same type of activity are included in the scope of the present disclosure. In addition, the compounds described herein can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like.The solvated forms of the compounds presented herein are also considered to be disclosed herein.

[0292] Compounds of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), also include crystalline and amorphous forms of those compounds, pharmaceutically acceptable salts, and active metabolites of these compounds having the same type of activity, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, unsolvated polymorphs (including anhydrates), conformational polymorphs, and amorphous forms of the compounds, as well as mixtures thereof.

[0293] The term “prodrug” as used herein, is intended to encompass compounds which, under physiologic conditions, are converted into pharmaceutical agents of the present disclosure. In some embodiments, term “prodrug”, is intended to encompass compounds which, under physiologic conditions, are converted into pharmaceutical agents of compounds or salts of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V). In certain embodiments, compounds or salts of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), may be prodrugs, e.g., wherein a hydroxyl in the parent compound is presented as an ester or a carbonate, a carboxylic acid is presented as an ester, or an aldehyde is presented as an imine. One method for making a prodrug is to include one or more selected moieties which are hydrolyzed under physiologic conditions to reveal the desired molecule. In other embodiments, the prodrug is converted by an enzymatic activity of the host animal such as specific target cells in the host animal.

[0294] In certain embodiments, compounds or salts of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), may be prodrugs, wherein the parent compound comprises of an aldehyde that may be presented as an imine. For example, the imine prodrug may be hydrolyzed enzymatically or chemically to furnish the parent aldehyde. As disclosed herein, imines are the preferred prodrugs of the present disclosure. In certain embodiments, imines are preferred prodrugs for compounds or salts of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V).

[0295] In certain embodiments, compounds or salts of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), may be prodrugs, e.g., wherein a hydroxyl in the parent compound is presented as an ester or a carbonate, or carboxylic acid present in the parent compound is presented as an ester. For example, esters or carbonates (e.g., esters or carbonates of alcohols or carboxylic acids and esters of phosphonic acids) are preferred prodrugs of the present disclosure.

[0296] Prodrugs are often useful because, in some situations, they may be easier to administer than the parent drug. They may, for instance, be bioavailable by oral administration whereas theparent is not. Prodrugs may help enhance the cell permeability of a compound relative to the parent drug. The prodrug may also have improved solubility in pharmaceutical compositions over the parent drug. Prodrugs may be designed as reversible drug derivatives, for use as modifiers to enhance drug transport to site-specific tissues or to increase drug residence inside of a cell.

[0297] In certain embodiments, the prodrug may be converted, e.g., enzymatically or chemically, to the parent compound under the conditions within a cell. In certain embodiments, the parent compound comprises an acidic moiety, e.g., resulting from the hydrolysis of the prodrug, which may be charged under the conditions within the cell. In particular embodiments, the prodrug is converted to the parent compound once it has passed through the cell membrane into a cell. In certain embodiments, the parent compound has diminished cell membrane permeability properties relative to the prodrug, such as decreased lipophilicity and increased hydrophilicity.

[0298] In some embodiments, the design of a prodrug increases the lipophilicity of the pharmaceutical agent. In some embodiments, the design of a prodrug increases the effective water solubility. See, e.g., Fedorak et al., Am. J. Physiol., 269:G210-218 (1995); McLoed et al., Gastroenterol, 106:405-413 (1994); Hochhaus et al., Biomed. Chrom., 6:283-286 (1992); J. Larsen and H. Bundgaard, Int. J. Pharmaceutics, 37, 87 (1987); J. Larsen et al., Int. J. Pharmaceutics, 47, 103 (1988); Sinkula et al., J. Pharm. Sci., 64:181-210 (1975); T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol.14 of the A.C.S. Symposium Series; and Edward B. Roche, Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, all incorporated herein for such disclosure). According to another embodiment, the present disclosure provides methods of producing the above-defined compounds. The compounds may be synthesized using conventional techniques. Advantageously, these compounds are conveniently synthesized from readily available starting materials.

[0299] Synthetic chemistry transformations and methodologies useful in synthesizing the compounds described herein are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations (1989); T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2d. Ed. (1991); L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis (1994); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis (1995). Pharmaceutical Formulations

[0300] In some aspects, the present disclosure provides a pharmaceutical composition comprising a compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), and at least one pharmaceutically acceptable excipient.

[0301] Pharmaceutical compositions can be formulated using one or more physiologically- acceptable carriers comprising excipients and auxiliaries. Formulation can be modified depending upon the route of administration chosen. Pharmaceutical compositions comprising a compound, salt or conjugate can be manufactured, for example, by lyophilizing the compound, salt or conjugate, mixing, dissolving, emulsifying, encapsulating or entrapping the conjugate. The pharmaceutical compositions can also include the compounds, salts or conjugates in a free- base form or pharmaceutically-acceptable salt form.

[0302] A compound or salt of any one of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), may be formulated in any suitable pharmaceutical formulation. A pharmaceutical formulation of the present disclosure typically contains an active ingredient (e.g., compound or salt of any one of Formula (I), (II), (II-A), (II- B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), and one or more pharmaceutically acceptable excipients or carriers, including but not limited to: inert solid diluents and fillers, diluents, sterile aqueous solution and various organic solvents, permeation enhancers, antioxidants, solubilizers, and adjuvants.

[0303] Pharmaceutical compositions may also be prepared from a compound or salt of any one of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV- C), or (V), and one or more pharmaceutically acceptable excipients. Preparations for such pharmaceutical composition are well-known in the art. See, e.g., Anderson, Philip O.; Knoben, James E.; Troutman, William G, eds., Handbook of Clinical Drug Data, Tenth Edition, McGraw-Hill, 2002; Pratt and Taylor, eds., Principles of Drug Action, Third Edition, Churchill Livingston, New York, 1990; Katzung, ed., Basic and Clinical Pharmacology, Ninth Edition, McGraw Hill, 2003; Goodman and Gilman, eds., The Pharmacological Basis of Therapeutics, Tenth Edition, McGraw Hill, 2001; Remingtons Pharmaceutical Sciences, 20th Ed., Lippincott Williams & Wilkins., 2000; Martindale, The Extra Pharmacopoeia, Thirty-Second Edition (The Pharmaceutical Press, London, 1999). Methods of Treatment

[0304] The compounds described herein can be used in the preparation of medicaments for the prevention or treatment of diseases or conditions. In addition, a method for treating any of the diseases or conditions described herein in a subject in need of such treatment, involvesadministration of pharmaceutical compositions containing at least one compound described herein, or a pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically acceptable solvate thereof, in therapeutically effective amounts to said subject.

[0305] The compositions containing the compound(s) described herein can be administered for prophylactic and / or therapeutic treatments. In therapeutic applications, the compositions are administered to a patient already suffering from a disease or condition, in an amount sufficient to cure or at least partially arrest the symptoms of the disease or condition. Amounts effective for this use will depend on the severity and course of the disease or condition, previous therapy, the patient's health status, weight, and response to the drugs, and the judgment of the treating physician.

[0306] In prophylactic applications, compositions containing the compounds described herein are administered to a patient susceptible to or otherwise at risk of a particular disease, disorder or condition. Such an amount is defined to be a "prophylactically effective amount or dose." In this use, the precise amounts also depend on the patient's state of health, weight, and the like. When used in a patient, effective amounts for this use will depend on the severity and course of the disease, disorder or condition, previous therapy, the patient's health status and response to the drugs, and the judgment of the treating physician.

[0307] In some aspects, the present disclosure provides a method for treatment, comprising administering to a subject in need thereof an effective amount of a compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V),.

[0308] In certain embodiments, the present disclosure provides a method of modulating CDK2. In some embodiments, the method of modulating CDK2 comprises administering to a subject in need thereof a compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), or a pharmaceutical composition thereof. In some embodiments, the administering is selective for CDK2 over a CDK selected from CDK1, CDK4, and CDK6. In some embodiments, the administering is selective for CDK2 over CDK1. In some embodiments, the administering is selective for CDK2 over CDK4. In some embodiments, the administering is selective for CDK2 over CDK6.

[0309] In certain embodiments, the present disclosure provides a method of inhibiting CDK2. In some embodiments, the method of inhibiting CDK2 comprises administering to a subject in need thereof a compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), or a pharmaceutical composition thereof. In some embodiments, the administering is selective for CDK2 over a CDK selected from CDK1, CDK4, and CDK6. In some embodiments, the administering is selective for CDK2 over CDK1. In someembodiments, the administering is selective for CDK2 over CDK4. In some embodiments, the administering is selective for CDK2 over CDK6.

[0310] In certain embodiments, the present disclosure provides a method of treating a disease or disorder mediated by CDK2. In some embodiments, the method of treating a disease or disorder mediated by CDK2 comprises administering to a subject in need thereof a compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), or a pharmaceutical composition thereof. In some embodiments, the disease or disorder is cancer. In some embodiments, the disease or disorder is selected from breast cancer, ovarian cancer, bladder cancer, uterine cancer, prostate cancer, lung cancer, esophageal cancer, head and neck cancer, colorectal cancer, kidney cancer, liver cancer, pancreatic cancer, stomach cancer, and thyroid cancer. In some embodiments, the administering is selective for CDK2 over a CDK selected from CDK1, CDK4, and CDK6. In some embodiments, the administering is selective for CDK2 over CDK1. In some embodiments, the administering is selective for CDK2 over CDK4. In some embodiments, the administering is selective for CDK2 over CDK6.

[0311] In certain embodiments, the present disclosure provides a method of inhibiting cell proliferation. In some embodiments, the method of inhibiting cell proliferation comprises administering to a subject in need thereof a compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), or a pharmaceutical composition thereof. In some embodiments, the cell proliferation is cancer cell proliferation. In some embodiments, the cancer cell proliferation is selected from breast cancer proliferation, ovarian cancer proliferation, bladder cancer proliferation, uterine cancer proliferation, prostate cancer proliferation, lung cancer proliferation, esophageal cancer proliferation, head and neck cancer proliferation, colorectal cancer proliferation, kidney cancer proliferation, liver cancer proliferation, pancreatic cancer proliferation, stomach cancer proliferation, and thyroid cancer proliferation. In some embodiments, the administering is selective for CDK2 over a CDK selected from CDK1, CDK4, and CDK6. In some embodiments, the administering is selective for CDK2 over CDK1. In some embodiments, the administering is selective for CDK2 over CDK4. In some embodiments, the administering is selective for CDK2 over CDK6.

[0312] In certain embodiments, the present disclosure provides a method of treating cancer. In some embodiments, the method of treating cancer comprises administering to a subject in need thereof a compound or salt of Formula (I), (II), (II-A), (II-B), (II-C), (II-D), (II-E), (II-F), (III), (IV), (IV-A), (IV-B), (IV-C), or (V), or a pharmaceutical composition thereof. In some embodiments, the cancer is selected from breast cancer, ovarian cancer, bladder cancer, uterine cancer, prostate cancer, lung cancer, esophageal cancer, head and neck cancer, colorectal cancer, kidney cancer, liver cancer, pancreatic cancer, stomach cancer, and thyroid cancer. In someembodiments, the administering is selective for CDK2 over a CDK selected from CDK1, CDK4, and CDK6. In some embodiments, the administering is selective for CDK2 over CDK1. In some embodiments, the administering is selective for CDK2 over CDK4. In some embodiments, the administering is selective for CDK2 over CDK6. CDK2 Protein

[0313] In some aspects, the present disclosure provides a CDK2 protein covalently bound to a compound, wherein the compound is covalently bound to a lysine residue of the CDK2 protein. In some embodiments, the compound is exogenous. In some embodiments, the exogenous compound is selected from an exogenous CDK2 inhibitor and an exogenous CDK2 activator. In some embodiments, the exogenous compound is an exogenous CDK2 modulator. In some embodiments, the exogenous compound is an exogenous CDK2 inhibitor.

[0314] In some embodiments, the CDK2 protein is selected from a wild-type CDK2 protein and a mutated CDK2 protein. In some embodiments, the CDK2 protein is a mutated CDK2 protein. In some embodiments, the CDK2 protein is a wild-type CDK2 protein.

[0315] In some embodiments, the exogenous compound is in contact with a lysine residue of the CDK2 protein as described herein. In some embodiments, the contact is between the lysine reside of the CDK2 protein and the exogenous compound is a covalent bond. In some embodiments, the lysine reside is selected from K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291. In some embodiments, the lysine residue is selected from K20, K33, K89, K129, K178, and K278. In some embodiments, the lysine residue is K89. In some embodiments, the lysine residue is selected from K20, K33, K129, K178, and K278. In some embodiments, the lysine residue is K20. In some embodiments, the lysine residue is K33. In some embodiments, the lysine residue is K129. In some embodiments, the lysine residue is K178. In some embodiments, the lysine residue is K278.

[0316] In some embodiments, the covalent bond between the exogenous compound and the lysine residue is a reversible covalent bond. In some embodiments, the reversible covalent bond is selected from a single bond, a double bound, and a triple bond. In some embodiments, the reversible covalent bond is a single bond. In some embodiments the reversible covalent bond is a double bond. In some embodiments, the reversible covalent bond is a triple bond. In some embodiments, the reversible covalent bond is a double bond between a carbon atom on the exogenous compound and the nitrogen atom on the sidechain of the lysine residue.

[0317] In some embodiments, the covalent bond between the exogenous compound and the lysine residue is a reversible covalent bond, wherein the lysine residue is selected from K6, K9,K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291. In some embodiments, the covalent bond between the exogenous compound and the lysine residue is a reversible covalent bond selected from a single bond, a double bound, and a triple bond, wherein the lysine residue is selected from K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291. In some embodiments, the covalent bond between the exogenous compound and the lysine residue is a reversible covalent single bond, wherein the lysine residue is selected from K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291. In some embodiments, the covalent bond between the exogenous compound and the lysine residue is a reversible covalent double bond, wherein the lysine residue is selected from K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291.

[0318] In some embodiments, the covalent bond between the exogenous compound and the lysine residue is a reversible covalent bond, wherein the lysine residue is selected from K20, K33, K89, K129, K178, and K278. In some embodiments, the covalent bond between the exogenous compound and the lysine residue is a reversible covalent bond, wherein the lysine residue is selected from K20, K33, K129, K178, and K278. In some embodiments, the covalent bond between the exogenous compound and the lysine residue is a reversible covalent bond, wherein the lysine residue is K89. In some embodiments, the covalent bond between the exogenous compound and the lysine residue is a reversible covalent bond selected from a single bond, a double bound, and a triple bond, wherein the lysine residue is K89. In some embodiments, the covalent bond between the exogenous compound and the lysine residue is a reversible covalent single bond, wherein the lysine residue is K89. In some embodiments, the covalent bond between the exogenous compound and the lysine residue is a reversible covalent double bond, wherein the lysine residue is K89.

[0319] In some embodiments, the reversible covalent bond in the in vivo CDK2 protein comprises a carbon-nitrogen interaction. In some embodiments, the carbon-nitrogen interaction is selected form a carbon-nitrogen single bond and a carbon-nitrogen double bond. In some embodiments, the carbon-nitrogen interaction is a carbon-nitrogen single bond. In some embodiments, the carbon-nitrogen interaction is a carbon-nitrogen double bond.

[0320] In some embodiments, the CDK2 protein is covalently bound with the exogenous compound, wherein the exogenous compound is bound at only one residue of the CDK2 protein. In some embodiments, the CDK2 protein is covalently bond with the exogenous compound via one covalent bond. In some embodiments, the CDK2 protein is covalently bound with the exogenous compound, wherein the exogenous compound is bound at one lysine residue. In someembodiments, the CDK2 protein has a single covalent bond between a lysine residue and the exogenous compound. In some embodiments, the CDK2 protein has a single covalent bond between K89 and the exogenous compound. In some embodiments, the CDK2 protein has a single covalent bond between K20 and the exogenous compound. In some embodiments, the CDK2 protein has a single covalent bond between K33 and the exogenous compound. In some embodiments, the CDK2 protein has a single covalent bond between K129 and the exogenous compound. In some embodiments, the CDK2 protein has a single covalent bond between K178 and the exogenous compound. In some embodiments, the CDK2 protein has a single covalent bond between K278 and the exogenous compound.

[0321] In some embodiments, the exogenous compound has reduced engagement at other lysine residues when covalently bound at a lysine residue selected from K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291. In some embodiments, the exogenous compound is in contact with one lysine residue selected from K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291, and has reduced engagement at the remaining lysine residues. In some embodiments, the exogenous compound is in contact with K89, and has reduced engagement at K6, K9, K20, K24, K33, K34, K56, K65, K88, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291. In some embodiments, the exogenous compound is in contact with K20, and has reduced engagement at K6, K9, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291. In some embodiments, the exogenous compound is in contact with K33, and has reduced engagement at K6, K9, K20, K24, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291. In some embodiments, the exogenous compound is in contact with K129, and has reduced engagement at K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K142, K178, K237, K242, K250, K273, K278, and K291. In some embodiments, the exogenous compound is in contact with K178, and has reduced engagement at K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K237, K242, K250, K273, K278, and K291. In some embodiments, the exogenous compound is in contact with K278, and has reduced engagement at K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291.

[0322] In some embodiments, the CDK2 protein has a single lysine residue covalently bound with the exogenous compound. In some embodiments, the CDK2 protein has a single lysine residue covalently bound with the exogenous compound, wherein the single lysine residue is selected from K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291. In some embodiments, the CDK2 protein has asingle lysine residue covalently bound with the exogenous compound, wherein the single lysine residue is K89. In some embodiments, the CDK2 protein has a single lysine residue covalently bound with the exogenous compound, wherein the single lysine residue is K20. In some embodiments, the CDK2 protein has a single lysine residue covalently bound with the exogenous compound, wherein the single lysine residue is K33. In some embodiments, the CDK2 protein has a single lysine residue covalently bound with the exogenous compound, wherein the single lysine residue is K129. In some embodiments, the CDK2 protein has a single lysine residue covalently bound with the exogenous compound, wherein the single lysine residue is K178. In some embodiments, the CDK2 protein has a single lysine residue covalently bound with the exogenous compound, wherein the single lysine residue is K278.

[0323] In some embodiments, the CDK2 protein is in vivo. In some embodiments, the CDK2 protein is in vitro. In some embodiments, the CDK2 protein is ex vivo. In some embodiments, the CDK2 protein is an in vivo engineered protein.

[0324] In some embodiments, the CDK2 protein is an in vivo engineered CDK2 protein, wherein the in vivo engineered CDK2 protein is generated by contacting the CDK2 protein in vivo with the exogenous compound. In some embodiments, the CDK2 protein is a mammalian in vivo engineered CDK2 protein, wherein the in vivo engineered CDK2 protein is generated by contacting the CDK2 protein in vivo with the exogenous compound. In some embodiments, the CDK2 protein is a human in vivo engineered CDK2 protein, wherein the in vivo engineered CDK2 protein is generated by contacting the CDK2 protein in vivo with the exogenous compound.

[0325] In some embodiments, the reversible covalent bond in the in vivo CDK2 protein is between a carbon atom and a nitrogen atom. In some embodiments, the reversible covalent bond in the in vivo CDK2 protein is between a carbon atom of the exogenous compound and a nitrogen atom of the lysine residue. In some embodiments, the reversible covalent bond in the in vivo CDK2 protein is between a carbon atom of the exogenous compound and a nitrogen atom of the lysine residue selected from K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291. In some embodiments, the reversible covalent bond in the in vivo CDK2 protein is between a carbon atom of the exogenous compound and a nitrogen atom of the K89 lysine residue. In some embodiments, the reversible covalent bond in the in vivo CDK2 protein is between a carbon atom of the exogenous compound and a nitrogen atom of the K20 lysine residue. In some embodiments, the reversible covalent bond in the in vivo CDK2 protein is between a carbon atom of the exogenous compound and a nitrogen atom of the K33 lysine residue. In some embodiments, the reversible covalent bond in the in vivo CDK2 protein is between a carbon atom of the exogenouscompound and a nitrogen atom of the K129 lysine residue. In some embodiments, the reversible covalent bond in the in vivo CDK2 protein is between a carbon atom of the exogenous compound and a nitrogen atom of the K178 lysine residue. In some embodiments, the reversible covalent bond in the in vivo CDK2 protein is between a carbon atom of the exogenous compound and a nitrogen atom of the K278 lysine residue.

[0326] In some embodiments, the reversible covalent bond in the in vivo CDK2 protein is a carbon-nitrogen double bond. In some embodiments, the reversible covalent bond in the in vivo CDK2 protein is a carbon-nitrogen double bond between the exogenous compound and the lysine residue. In some embodiments, the carbon-nitrogen double bond is between the exogenous compound and the lysine residue, wherein the lysine residue is selected from K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291. In some embodiments, the carbon-nitrogen double bond is between the exogenous compound and the K89 lysine residue. In some embodiments, the carbon-nitrogen double bond is between the exogenous compound and the K20 lysine residue. In some embodiments, the carbon-nitrogen double bond is between the exogenous compound and the K33 lysine residue. In some embodiments, the carbon-nitrogen double bond is between the exogenous compound and the K129 lysine residue. In some embodiments, the carbon-nitrogen double bond is between the exogenous compound and the K178 lysine residue. In some embodiments, the carbon-nitrogen double bond is between the exogenous compound and the K278 lysine residue.

[0327] In some embodiments, the carbon-nitrogen double bond is an imine bond. In some embodiments, the imine bond is between a carbon atom of the exogenous compound and a nitrogen atom of the lysine residue. In some embodiments, the imine bond is between the exogenous compound and the lysine residue, wherein the lysine residue is selected from K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291. In some embodiments, the imine bond is between the exogenous compound and the K89 lysine residue. In some embodiments, the imine bond is between the exogenous compound and the K20 lysine residue. In some embodiments, the imine bond is between the exogenous compound and the K33 lysine residue. In some embodiments, the imine bond is between the exogenous compound and the K129 lysine residue. In some embodiments, the imine bond is between the exogenous compound and the K178 lysine residue. In some embodiments, the imine bond is between the exogenous compound and the K278 lysine residue.

[0328] In some embodiments, the exogenous compound comprises a functional group. In some embodiments, the exogenous compound comprises an aldehyde functional group. In some embodiments, the reversible covalent bond is between the aldehyde functional group and thelysine residue. In some embodiments, the reversible covalent bond is between the aldehyde functional group and the lysine residue selected from K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291. In some embodiments, the reversible covalent bond is between the aldehyde functional group and the K89 lysine residue. In some embodiments, the reversible covalent bond is between the aldehyde functional group and the K20 lysine residue. In some embodiments, the reversible covalent bond is between the aldehyde functional group and the K33 lysine residue. In some embodiments, the reversible covalent bond is between the aldehyde functional group and the K129 lysine residue. In some embodiments, the reversible covalent bond is between the aldehyde functional group and the K178 lysine residue. In some embodiments, the reversible covalent bond is between the aldehyde functional group and the K278 lysine residue.

[0329] In some embodiments, the carbon-nitrogen bond is a reversible bond that results from a reversible reaction. In some embodiments, the carbon-nitrogen bond is a reversible bond that results from a reversible reaction between the exogenous compound and a lysine residue. In some embodiments, the carbon-nitrogen bond is a reversible bond that results from a reversible reaction between the exogenous compound and a lysine residue selected from K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291. In some embodiments, the carbon-nitrogen bond is a reversible bond that results from a reversible reaction between the exogenous compound and the K89 lysine residue. In some embodiments, the carbon-nitrogen bond is a reversible bond that results from a reversible reaction between the exogenous compound and the K20 lysine residue. In some embodiments, the carbon-nitrogen bond is a reversible bond that results from a reversible reaction between the exogenous compound and the K33 lysine residue. In some embodiments, the carbon-nitrogen bond is a reversible bond that results from a reversible reaction between the exogenous compound and the K129 lysine residue. In some embodiments, the carbon-nitrogen bond is a reversible bond that results from a reversible reaction between the exogenous compound and the K178 lysine residue. In some embodiments, the carbon-nitrogen bond is a reversible bond that results from a reversible reaction between the exogenous compound and the K278 lysine residue.

[0330] In some embodiments, the carbon-nitrogen double bond results from a reversible reaction between the amine functional group of a lysine residue and an aldehyde functional group on the exogenous compound. In some embodiments, the carbon-nitrogen double bond results from a reversible reaction between the amine functional group of a lysine residue and an aldehyde functional group on the exogenous compound, wherein the lysine residue is selected from K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237,K242, K250, K273, K278, and K291. In some embodiments, the carbon-nitrogen double bond results from a reversible reaction between the amine functional group of K89 and an aldehyde functional group on the exogenous compound. In some embodiments, the carbon-nitrogen double bond results from a reversible reaction between the amine functional group of K20 and an aldehyde functional group on the exogenous compound. In some embodiments, the carbon- nitrogen double bond results from a reversible reaction between the amine functional group of K33 and an aldehyde functional group on the exogenous compound. In some embodiments, the carbon-nitrogen double bond results from a reversible reaction between the amine functional group of K129 and an aldehyde functional group on the exogenous compound. In some embodiments, the carbon-nitrogen double bond results from a reversible reaction between the amine functional group of K178 and an aldehyde functional group on the exogenous compound. In some embodiments, the carbon-nitrogen double bond results from a reversible reaction between the amine functional group of K278 and an aldehyde functional group on the exogenous compound.

[0331] In some embodiments, the aldehyde functional group of the exogenous compound is an aromatic aldehyde. In some embodiments, the carbon-nitrogen double bond results from a reversible reaction between the amine functional group of a lysine residue and the aromatic aldehyde group on the exogenous compound. In some embodiments, the carbon-nitrogen double bond results from a reversible reaction between the amine functional group of a lysine residue and the aromatic aldehyde group on the exogenous compound, wherein the lysine residue is selected from K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291. In some embodiments, the carbon-nitrogen double bond results from a reversible reaction between the amine functional group of K89 and the aromatic aldehyde group on the exogenous compound. In some embodiments, the carbon- nitrogen double bond results from a reversible reaction between the amine functional group of K20 and the aromatic aldehyde group on the exogenous compound. In some embodiments, the carbon-nitrogen double bond results from a reversible reaction between the amine functional group of K33 and the aromatic aldehyde group on the exogenous compound. In some embodiments, the carbon-nitrogen double bond results from a reversible reaction between the ...

Claims

CLAIMS WHAT IS CLAIMED IS:

1. A compound represented by the structure of Formula (I):( ); or a pharmaceutically acceptable salt thereof wherein: Ring A is selected from C3-12carbocycle and 3- to 12-membered heterocycle; R5is selected from an electrophilic moiety or a prodrug thereof; each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, - S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, - SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; L is represented by -L1- L2-L3-L4-, wherein L1, L2, L3, and L4are each independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, - (R12)NC(O)N(R12)-, and–-(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted withone or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN; wherein L2, L3, and L4are each optionally absent; wherein no more than two of L1, L2, L3, and L4are selected from (a) and the two selected are not adjacent; R1and R2are each independently selected from (i), (ii), and (iii): (i) hydrogen, -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -C(O)OR14, -OC(O)R14, - N(R14)C(O)OR14, N(R14)C(O)R14, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, and -CN; (ii) C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), - CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; or R1and R2may come together to form a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, - C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, -N(R15)C(O)N(R15)2, - S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, -N(R15)C(O)N(R15)2, - S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN; R3is selected from: hydrogen, halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -C(O)OR16, -NO2, - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -C(O)OR16, - NO2, and -CN; R11, R12, R13, R14, R15, and R16are each independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted with one more substituents independently selected from halogen, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,-NO2, =O, -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein each C3-10carbocycle and 3- to 10-membered heterocycle are optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,-NO2, =O, and -CN; and C3-6carbocycle and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,-NO2, =O, and -CN; n is selected from 0, 1, 2, 3, and 4; and m is selected from 0 and 1.

2. The compound or salt of claim 1, wherein the electrophilic moiety is a lysine reactive electrophile.

3. The compound or salt of claim 2, wherein the lysine reactive electrophile is selected from a reversible lysine reactive electrophile and an irreversible lysine reactive electrophile.

4. The compound or salt of claim 1, wherein the electrophilic moiety is selected from a haloacetamide, a haloalkyl ketone, a halo amidine, a halo benzylphosphonate, an acyloxyalkyl ketone, a sulfonyl oxirane, an epoxide, a diazoalkyl ketone, a halotriazine, an acrylamide, a cyano acrylamide, a vinyl sulfone, a vinyl sulfonamide, an acrylate, an aldehyde, a borate, a halosulfonyl, an ester, squaric ester, squaramide ester, a fumarate, a carbonyl acrylate, a maleimide, a ketoamide, a nitrile, an alkene, an alkyne, a keto heterocycle, and an ynamide.

5. The compound or salt of claim 1, wherein the electrophilic moiety is selected from a haloacetamide, a haloalkyl ketone, a halo amidine, a halo benzylphosphonate, an acyloxyalkyl ketone, a sulfonyl oxirane, an epoxide, a diazoalkyl ketone, a halotriazine, an acrylamide, a cyano acrylamide, a vinyl sulfone, a vinyl sulfonamide, an acrylate, a fumarate, a carbonyl acrylate, a maleimide, a ketoamide, a nitrile, an alkene, an alkyne, a keto heterocycle, and an ynamide.

6. The compound or salt of claim 3, wherein the electrophilic moiety is selected an aldehyde, a borate, and a halosulfonyl.

7. The compound or salt of claim 1, wherein the electrophilic moiety or prodrug thereof is an aldehyde or a prodrug thereof.

8. The compound or salt of claim 7, wherein the aldehyde or a prodrug thereof is an imine.

9. The compound or salt of claim 1, wherein R5is an imine.

10. The compound or salt of claim 1, wherein R5is -C(R17)=N(R18); R17is selected from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR20, -SR20, -N(R20)2, -C(O)R20, -C(O)N(R20)2, - C(O)OR20, -OC(O)R20, -N(R20)C(O)OR20, -N(R20)C(O)R20, -S(O)R20, -S(O)2R20, - N(R20)S(O)2R20, -S(O)2N(R20)2, -NO2, =O, =S, =N(R20) and -CN; R18is selected from: hydrogen; C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -C(O)OR21, - OC(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)R21, -S(O)R21, -S(O)2R21, -N(R21)S(O)2R21, -S(O)2N(R21)2, -P(=O)(OR21)2, -NO2, =O, =S, =N(R21), -CN, C3-10carbocycle, and 3- to 10- membered heterocycle; and C3-10carbocycle and 3- to 10- membered heterocycle, any of which are optionally substituted with one or more substituents independently selected from halogen, -OR21, - SR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -C(O)OR21, -OC(O)R21, -N(R21)C(O)OR21, - N(R21)C(O)R21, -S(O)R21, -S(O)2R21, -N(R21)S(O)2R21, -S(O)2N(R21)2, -NO2, =O, =S, =N(R21), -CN, C1-6alkyl, and C1-6haloalkyl; and R20and R21are each independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted with one more substituents independently selected from halogen, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2, -NO2, =O, -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein each C3-10carbocycle and 3- to 10-membered heterocycle are optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2, -NO2, =O, and -CN; and C3-6carbocycle and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2, -NO2, =O, and -CN.

11. The compound or salt of any one of claims 1 to 10, wherein the structure of Formula (I) is represented by the structure of Formula (II):

12. The compound or salt of claim 10 or claim 11, wherein R17is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

13. The compound or salt of claim 12, wherein R17is hydrogen.

14. The compound or salt of any one of claims 10 to 13, wherein R18is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

15. The compound or salt of claim 14, wherein R18is selected from hydrogen,,16. The compound or salt of any one of claims 10 to 13, wherein R18is C1-6alkyl substituted with one or more substituents independently selected from -OR21, -SR21, -N(R21)2, -C(O)R21, - C(O)N(R21)2, -C(O)OR21, -OC(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)R21, -S(O)R21, -S(O)2R21, -N(R21)S(O)2R21, -S(O)2N(R21)2, -P(=O)(OR21)2, -NO2, =O, =S, =N(R21), and -CN.

17. The compound or salt of claim 16, wherein R18is C1-6alkyl substituted with one or more substituents independently selected from -OR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -C(O)OR21, - S(O)2R21, -P(=O)(OR21)2, -NO2, =O, and -CN, wherein R21is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

18. The compound or salt of claim 17, wherein R18is selected from,19. The compound or salt of any one of claims 10 to 13, wherein R18is C1-6alkyl substituted with one or more substituents independently selected from C3-10carbocycle and 3- to 10- membered heterocycle.

20. The compound or salt of claim 19, wherein R18is C1-6alkyl substituted with one or more C3-6carbocycle.

21. The compound or salt of claim 20, wherein R18is selected from.

22. The compound or salt of any one of claims 10 to 13, wherein R18is selected from C3-10carbocycle and 3- to 10-membered heterocycle, any of which are optionally substituted with one or more substituents independently selected from halogen, -OR21, -SR21, -N(R21)2, -C(O)R21, - C(O)N(R21)2, -C(O)OR21, -OC(O)R21, -N(R21)C(O)OR21, -N(R21)C(O)R21, -S(O)R21, -S(O)2R21, -N(R21)S(O)2R21, -S(O)2N(R21)2, -NO2, =O, =S, =N(R21), -CN, C1-6alkyl, and C1-6haloalkyl.

23. The compound or salt of claim 22, wherein R18is selected from C3-6carbocycle and 3- to 6-membered heterocycle, any of which are optionally substituted with one or more substituents selected from halogen, -OR21, -N(R21)2, -C(O)R21, -C(O)N(R21)2, -C(O)OR21, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl.

24. The compound or salt of claim 23, wherein R18is.

25. The compound or salt of claim 10 or claim 11, whereinis selected from:

26. The compound or salt of any one of claims 10 to 25, wherein m is 1.

27. The compound or salt of any one of claims 10 to 26, wherein R3is selected from hydrogen and C1-6alkyl and C1-6haloalkyl.

28. The compound or salt of claim 27, wherein R3is hydrogen.

29. The compound or salt of any one of claims 10 to 28, wherein R4is independently selected from halogen, -OR11, -N(R11)2, -NO2, -CN, C1-6alkyl, and C1-6haloalkyl.

30. The compound or salt of claim 29, wherein R4is selected from -OH, -OMe, and methyl.

31. The compound or salt of any one of claims 10 to 30, wherein n is selected from 1 and 2.

32. The compound or salt of any one of claims 10 to 31, wherein Ring A is selected from C3-10carbocycle and 3- to 10-membered heterocycle.

33. The compound or salt of claim 32, wherein Ring A is C6-10carbocycle.

34. The compound or salt of claim 33, wherein Ring A is a bicyclic C6-10 carbocycle.

35. The compound or salt of claim 34, wherein the bicyclic C6-10carbocycle of Ring A is selected from C6-10fused carbocycle, C6-10bridged carbocycle, and C6-10spirocyclic carbocycle.

36. The compound or salt of claim 35, wherein Ring A is C6-10 fused carbocycle.

37. The compound or salt of claim 36, wherein Ring A is dihydroindenyl.

38. The compound or salt any one of claims 7 to 11, whereinis selected, , , , , ,39. The compound or salt of any one of claims 10 to 31, wherein Ring A is selected from C3-8 carbocycle and 3- to 8-membered heterocycle.

40. The compound or salt of claim 39, wherein Ring A is C3-8 carbocycle.

41. The compound or salt of claim 40, wherein Ring A is phenyl.

42. The compound or salt of any one of claims 10 to 41, wherein one of R1and R2is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl, and the other is selected from: -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -CN and, C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, , wherein the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from halogen, -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -NO2, =O, and -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which are optionally substituted with halogen, -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -NO2, =O, - CN, C1-6alkyl, and C1-6haloalkyl.

43. The compound or salt of claim 42, wherein one of R1and R2is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl, and the other is selected from: -OR14, -N(R14)2, C1-6alkyl, and C2-6alkynyl, , wherein the C1-6alkyl and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from halogen, -OR14, -N(R14)2, and -CN; andC3-10carbocycle and 3- to 10-membered heterocycle, each of which are optionally substituted with halogen, C1-6alkyl and C1-6haloalkyl.

44. The compound or salt of claim 43, wherein one of R1and R2is selected from hydrogen, methyl, ethyl, and propyl, and the other is selected from methyl, ethyl, propyl,, ,45. The compound or salt of any one of claims 10 to 41, wherein R1and R2come together to form a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -NO2, =O, -CN, C1-6alkyl, and C1-6haloalkyl.

46. The compound or salt of claim 45, whereinis selected from, ,.

47. The compound or salt of any one of claims 10 to 46, wherein L4is absent and each of L1, L2, and L3are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -N(R12)C(O)-, and -N(R12)C(O)O-; and (b) C1-6alkylene optionally substituted with one or more substituents independently selected from halogen, -OR13, -N(R13)2, and -CN.

48. The compound or salt of claim 47, wherein L is selected from.

49. The compound or salt of claim 47, wherein L is.

50. The compound or salt of claim 11, wherein the compound of Formula (II) is selected from a compound in Table 1A.

51. The compound or salt of claim 7, wherein the aldehyde or a prodrug thereof is an aldehyde.

52. The compound or salt of claim 1, wherein R5is an aldehyde.

53. The compound or salt of claim 1, wherein R5is -C(O)H.

54. The compound or salt of any one of claims 1 to 3, 4 to 7, and 50 to 53, wherein the structure of Formula (I) is represented by the structure of Formula (III):

55. The compound or salt of claim 54, wherein R1and R2are each independently selected from hydrogen, -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -C(O)OR14, -OC(O)R14, - N(R14)C(O)OR14, N(R14)C(O)R14, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, and - CN.

56. The compound or salt of claim 55, wherein R1and R2are each independently selected from hydrogen, -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, and -CN.

57. The compound or salt of claim 56, wherein R1and R2are each independently selected from hydrogen, -OR14, and -N(R14)2; and each R14is independently selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

58. The compound or salt of claim 57, wherein R1and R2are each independently selected from59. The compound or salt of claim 57, wherein R1and R2are each independently selected.

60. The compound or salt of claim 54, wherein R1and R2are each independently selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN.

61. The compound or salt of claim 54, wherein one of R1and R2is selected from hydrogen and C1-6alkyl and the other is selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, - OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, - N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN.

62. The compound or salt of claim 61, wherein one of R1and R2is selected from hydrogen and C1-6alkyl and the other is selected from C2-6alkynyl optionally substituted with one or more substituents independently selected from halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN.

63. The compound or salt of claim 62, wherein one of R1and R2is selected from hydrogen and C1-6alkyl and the other is selected from C2-6alkynyl optionally substituted with one or more substituents independently selected from halogen, -OR14, -N(R14)2, -NO2, and -CN.

64. The compound or salt of claim 63, wherein one of R1and R2is selected from hydrogenand C1-6 alkyl and the other is selected from.

65. The compound or salt of claim 54, wherein R1and R2are each independently selected from C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, - N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, - NO2, =O, =S, =N(R14), and -CN.

66. The compound or salt of claim 54, wherein one of R1and R2is selected from hydrogen and C1-6alkyl, and the other is selected from C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, - OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, - N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN.

67. The compound or salt of claim 66, wherein one of R1and R2is selected from hydrogen and C1-6alkyl, and the other is C3-10carbocycle optionally substituted with C2-6alkynyl, the C2-6alkynyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, - OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, - N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN.

68. The compound or salt of claim 67, wherein one of R1and R2is selected from hydrogen and C1-6alkyl, and the other is C3-10carbocycle substituted with C2-6alkynyl, the C2-6alkynyl optionally substituted with one or more substituents independently selected from halogen, - OR14, -N(R14)2, -C(O)R14, -NO2, and -CN.

69. The compound or salt of claim 68, wherein one of R1and R2is selected from hydrogenand C1-6 alkyl, and the other i.

70. The compound or salt of claim 54, wherein one of R1and R2is selected from hydrogen and C1-6alkyl, and the other is selected from -OR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, and -CN.

71. The compound or salt of claim 70, wherein one of R1and R2is selected from hydrogen and C1-6alkyl, and the other is selected from -N(R14)2.

72. The compound or salt of claim 71, wherein -N(R14)2 is selected from -NMe2,73. The compound of claim 54, wherein R1and R2may come together to form a 3- to 10- membered heterocycle optionally substituted with one or more substituents independently selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, wherein the C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, - OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, -N(R15)C(O)N(R15)2, -S(O)R15, -S(O)2R15, - N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN.

74. The compound or salt of claim 73, wherein R1and R2may come together to form a 3- to 10-membered heterocycle optionally substituted with C2-6alkynyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, - N(R15)C(O)N(R15)2, -S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN.

75. The compound or salt of claim 74, wherein R1and R2may come together to form a 3- to 10-membered heterocycle optionally substituted with C2-6alkynyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, and -CN.

76. The compound or salt of claim 75, wherein.

77. The compound of claim 54, wherein R1and R2may come together to form a 3- to 10- membered heterocycle optionally substituted with one or more substituents independently selected from C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, - C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, -N(R15)C(O)N(R15)2, -S(O)R15, - S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN.

78. The compound of claim 77, wherein R1and R2may come together to form a 3- to 10- membered heterocycle optionally substituted C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, and -CN.alt of claim 73, wherein is selected from,80. The compound or salt of claim 54, wherein selected from81. The compound of any one of claims 54 to 77, wherein R3is selected from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -C(O)OR16, -NO2, and -CN.

82. The compound of claim 81, wherein R3is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

83. The compound of claim 82, wherein R3is selected from hydrogen.

84. The compound or salt of any one of claims 54 to 83, wherein Ring A is selected from C3-10carbocycle and 3- to 10-membered heterocycle.

85. The compound or salt of claim 84, wherein Ring A is C6-10carbocycle.

86. The compound or salt of claim 85, wherein Ring A is a bicyclic C6-10 carbocycle.

87. The compound or salt of claim 86, wherein the bicyclic C6-10 carbocycle of Ring A is selected from C6-10fused carbocycle, C6-10bridged carbocycle, and C6-10spirocyclic carbocycle.

88. The compound or salt of claim 87, wherein Ring A is C6-10 fused carbocycle.

89. The compound or salt of claim 88, wherein Ring A is dihydroindenyl.

90. The compound or salt of any one of claims 54 to 89, wherein91. The compound or salt of claim 85, wherein Ring A is phenyl.

92. The compound or salt of any one of claims 54 to 85, or claim 91, whereinis.

93. The compound or salt of any one of claims 54 to 92, wherein L is selected from.

94. The compound or salt of claim 1 or claim 54, wherein the structure of Formula (I) or Formula (III) is represented by the structure of Formula (IV):or a pharmaceutically acceptable salt thereof wherein: Ring A is selected from C3-12 carbocycle and 3- to 12-membered heterocycle, each R4is independently selected at each occurrence from:halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, - S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, - SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; L is represented by -L1- L2-L3-L4-, wherein L1, L2, L3, and L4are each independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, - N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, - (R12)NC(O)N(R12)-, and–-(R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN; wherein L2, L3, and L4are each optionally absent; wherein no more than two of L1, L2, L3, and L4are selected from (a) and the two selected are not adjacent; R1and R2are each independently selected from (i), (ii), and (iii): (i) hydrogen; (ii) C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), -CN; and C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and (iii) C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, - C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, - OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, - S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; or R1and R2may come together to form a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, - C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, -N(R15)C(O)N(R15)2, - S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, -N(R15)C(O)N(R15)2, - S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN; R3is selected from: hydrogen, halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -C(O)OR16, -NO2, - CN; and C1-6alkyl optionally substituted with one or more substituents independentlyselected from halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -C(O)OR16, - NO2, and -CN; R11, R12, R13, R14, R15, and R16are each independently selected at each occurrence from: hydrogen; C1-6alkyl optionally substituted with one more substituents independently selected from halogen, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,-NO2, =O, -CN, C3-10carbocycle, and 3- to 10-membered heterocycle, wherein each C3-10carbocycle and 3- to 10-membered heterocycle are optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,-NO2, =O, and -CN; and C3-6carbocycle and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OH, -O-C1-6alkyl, -O-C1-6haloalkyl, -NH2,-NO2, =O, and -CN; n is selected from 0, 1, 2, 3, and 4; and m is selected from 0 and 1.

95. The compound or salt of claim 94, wherein m is 1 and the structure of Formula (IV) is represented by Formula (IV-A):

96. The compound or salt of claim 94 or claim 95, wherein the structure of Formula (IV) is represented by the structure of Formula (IV-B):

97. The compound or salt of claim 94 or claim 95, wherein the structure of Formula (IV) is represented by the structure of Formula (IV-C):

98. The compound or salt of any one of claims 94 to 97, wherein Ring A is C3-12 carbocycle.

99. The compound or salt of claim 98, wherein Ring A is C5-9carbocycle.

100. The compound or salt of claim 99, wherein Ring A is selected from phenyl and 2,3- dihydro-1H-indenyl.

101. The compound or salt of claim 100, wherein Ring A is selected from phenyl and 2,3- dihydro-1H-indenyl; n is 0.

102. The compound or salt of claim 101, wherein103. The compound or salt of claim 101, wherein104. The compound or salt of claim of any one of claims 98 to 100, wherein n is 1 and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, - N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

105. The compound or salt of claim 104, wherein n is 1; R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

106. The compound or salt of claim 105, whereinis selected from:, and .

107. The compound or salt of claim 105, whereinis selected from:

108. The compound or salt of any one of claims 98 to 100, wherein n is 1 and R4is independently selected from C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, - OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, - S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN.

109. The compound or salt of claim 108, wherein n is 1 and R4is independently selected from C1-6alkyl and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, - N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

110. The compound or salt of claim 109, wherein n is 1 and R4is independently selected from C1-6alkyl and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

111. The compound or salt of claim 110, wherein112. The compound or salt of any one of claims 98 to 100, wherein n is 1 and R4is independently selected from C3-10carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, - OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, - S(O)2N(R11)2, -NO2, and -CN.

113. The compound or salt of claim 112, wherein n is 1 and R4is independently selected from 3- to 6-membered heteroaryl optionally substituted with one or more substituents independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, - S(O)2N(R11)2, -NO2, and -CN.

114. The compound or salt of claim 113, wherein115. The compound or salt of any one of claims 98 to 100, wherein n is 2 and each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, - S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, - N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, - N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

116. The compound or salt of claim 115, wherein n is 2 and each R4is independently selected at each occurrence from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)R11, -N(R11)C(O)OR11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, - S(O)2N(R11)2, -NO2, and -CN; andR11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

117. The compound or salt of claim 116, whereinis selected from: ,118. The compound or salt of claim 116, whereinselected from:, , ,119. The compound or salt of any one of claims 98 to 100, wherein n is 2 and each R4is independently selected at each occurrence from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, - S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, - C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, - S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN.

120. The compound or salt of any one of claim 119, wherein n is 2 and each R4is independently selected at each occurrence from: halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)R11, -N(R11)C(O)OR11, - N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR11, -N(R11)2, -C(O)R11, - N(R11)C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN.

121. The compound or salt of claim 120, wherein122. The compound or salt of any one of claims 98 to 100, wherein n is 3 and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, - N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

123. The compound or salt of claim 122, wherein124. The compound or salt of any one of claims 94 to 97, wherein Ring A is 3- to 12- membered heterocycle.

125. The compound or salt of claim 124, wherein Ring A is selected from 3- to 8-membered monocyclic heterocycle and 8- to 12-membered bicyclic heterocycle.

126. The compound or salt of claim 125, wherein Ring A is selected from pyridyl, isoindolinyl, dihydrobenzofuranyl, indazolyl, benzo[d]thiazolyl, and isoquinolinyl, and isoquinolinyl.

127. The compound or salt of claim 126, wherein n is 0.

128. The compound or salt of claim 127, wherein is selected from.

129. The compound or salt of any one of claims 124 to 126, wherein n is 1 and R4is independently selected from halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, - N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

130. The compound or salt of claim 129, wherein n is 1 and R4is independently selected from halogen, -OR11, -N(R11)2, -C(O)R11, -N(R11)C(O)OR11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, and -CN; and R11is selected from hydrogen, C1-6alkyl, and C1-6haloalkyl.

131. The compound or salt of claim 130, wherein is selected from.

132. The compound or salt of any one of claims 94 to 97, whereinis selected,133. The compound or salt of any one of claims 94 to 97, whereinis selected134. The compound or salt of any one of claims 94 to 133, wherein each of L2, L3and L4are absent and L1is selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and–- (R12)NC(O)N(R12)N(R12)-; and(b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10- membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN.

135. The compound or salt of claim 134, wherein L1is selected from -N(R12)C(O)-, - N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and–-(R12)NC(O)N(R12)N(R12)-; and R12is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

136. The compound or salt of claim 135, wherein L1is selected from -N(R12)C(O)-, - N(R12)C(O)C(O)N(R12)-, and–-(R12)NC(O)N(R12)-; and R12is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

137. The compound or salt of claim 135, wherein L1is selected from -N(R12)- , -N(R12)C(O)-, -N(R12)C(O)C(O)N(R12)-, and–-(R12)NC(O)N(R12)-; and R12is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

138. The compound or salt of claim 136, wherein L is selected from: ,139. The compound or salt of claim 137, wherein L is selected from:, ,140. The compound or salt of claim of any one of claims 94 to 133, wherein each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, - N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, -S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and–-(R12)NC(O)N(R12)N(R12)-; and(b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10- membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN.

141. The compound or salt of claim 139, wherein each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, and–-(R12)NC(O)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN.

142. The compound or salt of claim 141, wherein each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -O-, -N(R12)-, -N(R12)C(O)-, and -N(R12)C(O)O-; and (b) C1-6alkylene and C2-6alkenylene, each of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

143. The compound or salt of claim 142, wherein L is selected from:,144. The compound or salt of claim 141, wherein each of L3and L4are absent and each of L1and L2are independently selected from (a) and (b): (a) -N(R12)-, -N(R12)C(O)-, -N(R12)C(O)O-, and–-(R12)NC(O)N(R12)-; andĨb) C3-10carbocyclene and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

146. The compound or salt of claim 142 or claim 145, wherein L is selected from:

147. The compound or salt of any one of claims 94 to 133, wherein L4is absent and each of L1, L2, and L3are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and–- (R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10- membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN.

148. The compound or salt of claim 147, wherein L4is absent and each of L1, L2, and L3are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -N(R12)C(O)-, and -N(R12)C(O)O-; and (b) C1-6alkylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10-membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, halogen, -OR13, - CN, C1-6alkyl; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

149. The compound or salt of claim 148, wherein L is selected from:,150. The compound or salt of any one of claims 94 to 133, wherein each of L1, L2, L3and L4are independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and–- (R12)NC(O)N(R12)N(R12)-; andĨb) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10- membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN; and R13is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

151. The compound or salt of claim 150, wherein L is selected from:,, and .

152. The compound or salt of any one of claims 94 to 133, wherein L is selected from:

153. The compound or salt of any one of claims 94 to 133, wherein L is selected from:, , ,,, ,, ,154. The compound or salt of any one of claims 94 to 153, wherein one of R1or R2is hydrogen.

155. The compound or salt of any one of claims 94 to 153, wherein one of R1or R2is selected from hydrogen and the other of R1or R2is selected from C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, - S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, - SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, - N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, - N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, - SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, - N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN.

156. The compound or salt of claim 155, wherein one of R1or R2is selected from hydrogen and the other of R1or R2is selected from C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, - S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and C3-6carbocycle optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, -CN; and R14is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

157. The compound or salt of claim 156, wherein one of R1or R2is selected from hydrogen and the other of R1 or R2 is selected from158. The compound or salt of claim 156, wherein one of R1or R2is selected from hydrogen159. The compound or salt of claim 155, wherein one of R1or R2is selected from hydrogen and the other of R1or R2is selected from C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, - S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and 3- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, - CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, -CN; and R14is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

160. The compound or salt of claim 159, wherein in one of R1or R2is selected from hydrogen and the other of R1or R2is selected from, , , and.

161. The compound or salt of claim 155, wherein one of R1or R2is selected from hydrogen and the other of R1 or R2 is selected from, , , , , ,162. The compound or salt of any one of claims 94 to 152, wherein one of R1or R2is selected from hydrogen and the other of R1or R2is selected from C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, -N(R14)C(O)R14, - C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, -N(R14)C(O)N(R14)2, - S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN.

163. The compound or salt of claim 162, wherein one of R1or R2is selected from hydrogen and the other of R1or R2is selected from C3-6carbocycle and 3- to 6-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, =O, =S, =N(R14), and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, =O, =S, =N(R14), and -CN; and R14is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

164. The compound or salt of claim 163, wherein one of R1or R2is selected from hydrogen and the other of R1or R2is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and tetrahydropyranyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, =O, =S, =N(R14), and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, =O, =S, =N(R14), and -CN; and R14is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

165. The compound or salt of claim 163, wherein one of R1or R2is selected from hydrogen and the other of R1or R2is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentyl, oxetanyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, pyridyl, and phenyl,each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, =O, =S, =N(R14), and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR14, -N(R14)2, -C(O)R14, -NO2, =O, =S, =N(R14), and -CN; and R14is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

166. The compound or salt of claim 164, wherein one of R1or R2is selected from hydrogenand the other of R1 or R2 is selected from:, , , , ,167. The compound or salt of claim 164, wherein one of R1or R2is selected from hydrogenand the other of R1 or R2 is selected from:, , , , , ,168. The compound or salt of claim 164, wherein one of R1or R2is selected from hydrogen169. The compound or salt of claim 164, wherein one of R1or R2is selected from hydrogenand the other of R1 or R2 is selected from:, , , , ,170. The compound or salt of claim 165, wherein one of R1or R2is selected from hydrogenand the other of R1 or R2 is selected from:, , , , ,171. The compound or salt of claim 165, wherein one of R1or R2is selected from hydrogen172. The compound or salt of any one of claims 94 to 152, wherein one of R1or R2is selectedfrom hydrogen and the other of R1 or R2 is selected from, , , , ,173. The compound or salt of any one of claims 94 to 152, wherein one of R1or R2is selected174. The compound or salt of any one of claims 94 to 152, wherein one of R1or R2is selectedfrom hydrogen and the other of R1 or R2 is selected from, , , , ,175. The compound or salt of any one of claims 94 to 153, wherein R1and R2may come together to form a 3- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, - C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, -N(R15)C(O)N(R15)2, - S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -SR15, -N(R15)2, -C(O)R15, -C(O)N(R15)2, -N(R15)C(O)R15, -C(O)OR15, -OC(O)R15, -N(R15)C(O)OR15, -OC(O)N(R15)2, -N(R15)C(O)N(R15)2, - S(O)R15, -S(O)2R15, -N(R15)S(O)2R15, -S(O)2N(R15)2, -NO2, =O, =S, =N(R15), and -CN.

176. The compound or salt of claim 175, wherein R1and R2may come together to form a 3- to 6-membered saturated heterocycle optionally substituted with one or more substituentsindependently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, =O, =S, =N(R15), -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, =O, =S, =N(R15), and -CN; and R15is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

177. The compound or salt of claim 175, wherein R1and R2may come together to form a 3- to 8-membered saturated heterocycle optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, =O, =S, =N(R15), -CN; and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR15, -N(R15)2, -C(O)R15, -NO2, =O, =S, =N(R15), and -CN; and R15is independently selected at each occurrence from hydrogen, C1-6alkyl, and C1-6haloalkyl.

178. The compound or salt of claim 176, wherein is selected from179. The compound or salt of claim 176, whereinis selected from,180. The compound or salt of claim 177, whereinis selected from,181. The compound or salt of claim 94, wherein Ring A is selected from C3-6carbocycle and 3- to 6-membered heterocycle.

182. The compound or salt of claim 181, wherein n is selected from 0, 1, and 2.

183. The compound or salt of claim 181 or claim 182, wherein R4is selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, - S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; C1-6alkyl, C2-6alkenyl, and C2-6alkynyl, each of which is optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, - OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, - NO2, =O, =S, =N(R11), and -CN.

184. The compound or salt of claim 183, wherein R4 is selected from ethyl,, ,.

185. The compound or salt of claim 181 or claim 182, wherein R4is selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, -C(O)N(R11)2, -N(R11)C(O)R11, - C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, -N(R11)C(O)N(R11)2, -S(O)R11, - S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN; 5- to 6-membered heterocycle optionally substituted with one or more substituents independently selected from: halogen, -OR11, -SR11, -N(R11)2, -C(O)R11, - C(O)N(R11)2, -N(R11)C(O)R11, -C(O)OR11, -OC(O)R11, -N(R11)C(O)OR11, -OC(O)N(R11)2, - N(R11)C(O)N(R11)2, -S(O)R11, -S(O)2R11, -N(R11)S(O)2R11, -S(O)2N(R11)2, -NO2, =O, =S, =N(R11), and -CN.

186. The compound or salt of claim 185, wherein R4is.

187. The compound or salt of any one of claims 181 to 186, wherein L is represented by -L1- L2-L3-L4-, wherein L1, L2, L3, and L4are each independently selected from (a) and (b): (a) -O-, -N(R12)-, -S-, -S(O)-, -S(O)2-, -S(O)(NR12)-, -N(R12)C(O)-, -N(R12)C(O)O-, -N(R12)C(O)C(O)N(R12)-, -N(R12)S(O)2-, -N(R12)S(O)2N(R12)-, - S(O)(NR12)N(R12)-, -N(R12)N(R12)-, -(R12)NC(O)N(R12)-, and–- (R12)NC(O)N(R12)N(R12)-; and (b) C1-6alkylene, C2-6alkenylene, C2-6alkynylene, C3-10carbocyclene, and 3- to 10- membered heterocyclene, any one of which is optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, -CN, C1-6alkyl and C3-6carbocycle, wherein the C1-6alkyl and C3-6carbocycle are each optionally substituted with one or more substituents independently selected from halogen, -OR13, -SR13, =O, =S, and -CN.

188. The compound or salt of any one of claims 181 to 187, wherein R3is selected from hydrogen and C1-6alkyl optionally substituted with one or more substituents independently selected from halogen, -OR16, -SR16, -N(R16)2, -C(O)R16, -C(O)N(R16)2, -C(O)OR16, -NO2, and - CN.

189. The compound or salt of any one of claims 181 to 188, wherein R1or R2is hydrogen.

190. The compound or salt of any one of claims 181 to 188, wherein R1or R2is selected from: C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and C3-6carbocycle optionally substituted with one or more substituents independently selected from halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), -CN, C1-6alkyl, and C1-6haloalkyl.

191. The compound or salt of any one of claims 181 to 188, one of R1and R2is selected from hydrogen and the other of R1or R2is selected from: C1-6alkyl optionally substituted with one or more substituents independently selected from: halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), and -CN; and C3-6carbocycle optionally substituted with one or more substituents independently selected from halogen, -OR14, -SR14, -N(R14)2, -C(O)R14, -C(O)N(R14)2, - N(R14)C(O)R14, -C(O)OR14, -OC(O)R14, -N(R14)C(O)OR14, -OC(O)N(R14)2, - N(R14)C(O)N(R14)2, -S(O)R14, -S(O)2R14, -N(R14)S(O)2R14, -S(O)2N(R14)2, -NO2, =O, =S, =N(R14), -CN, C1-6alkyl, and C1-6haloalkyl.

192. The compound or salt of claim 94, wherein m is 0 and the structure of Formula (IV) is represented by Formula193. The compound or salt of claim 54 or claim 94, wherein the compound of Formula (III) or Formula (IV) is selected from a compound in Table 1.

194. A pharmaceutical composition comprising a compound or salt of any one of claims 1 to 193, and a pharmaceutically acceptable excipient.

195. A method of modulating CDK2 comprising, administering to a subject in need thereof a compound or salt of any one of claims 1 to 193, or a pharmaceutical composition of claim 194.

196. A method of inhibiting CDK2 comprising, administering to a subject in need thereof a compound or salt of any one of claims 1 to 193, or a pharmaceutical composition of claim 194.

197. A method of treating a disease or disorder mediated by CDK2 comprising, administering to a subject in need thereof a compound or salt of any one of claims 1 to 193, or a pharmaceutical composition of claim 194.

198. A method of inhibiting cell proliferation comprising, administering to a subject in need thereof a compound or salt of any one of claims 1 to 193, or a pharmaceutical composition of claim 194.

199. The method of claim 198, wherein the cell proliferation is cancer cell proliferation.

200. The method of claim 199, wherein the cancer cell proliferation is selected from breast cancer proliferation, ovarian cancer proliferation, bladder cancer proliferation, uterine cancer proliferation, prostate cancer proliferation, lung cancer proliferation, esophageal cancer proliferation, head and neck cancer proliferation, colorectal cancer proliferation, kidney cancer proliferation, liver cancer proliferation, pancreatic cancer proliferation, stomach cancer proliferation, and thyroid cancer proliferation.

201. A method of treating cancer comprising, administering to a subject in need thereof a compound or salt of any one of claims 1 to 193, or a pharmaceutical composition of claim 194.

202. The method of claim 201, wherein the cancer is selected from breast cancer, ovarian cancer, bladder cancer, uterine cancer, prostate cancer, lung cancer, esophageal cancer, head and neck cancer, colorectal cancer, kidney cancer, liver cancer, pancreatic cancer, stomach cancer, and thyroid cancer.

203. The method of any one of claims 195 to 202, wherein the administering is selective for CDK2 over a CDK selected from CDK1, CDK4, and CDK6.

204. A CDK2 protein covalently bound to a compound, wherein the compound is covalently bound to a lysine residue of the CDK2 protein.

205. The CDK2 protein of claim 204, wherein the compound is an exogenous CDK2 modulator.

206. The CDK2 protein of claim 204, wherein the compound is an exogenous CDK2 inhibitor.

207. The CDK2 protein of claim 206, wherein the exogenous CDK2 inhibitor is a compound or salt of claim 1, or a pharmaceutical composition of claim 194.

208. The CDK2 protein of any one of claims 204 to 207, wherein the lysine residue is selected from K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291.

209. The CDK2 protein of claim 208, wherein the lysine residue is selected from K20, K33, K89, K129, K178, and K278.

210. The CDK2 protein of claim 208, wherein the lysine residue is K89 211. The CDK2 protein of any one of claims 204 to 210, wherein the CDK2 protein is in vivo.

212. The CDK2 protein of claim 211, wherein the CDK2 protein is an in vivo engineered CDK2 protein, wherein the in vivo engineered CDK2 protein is generated by contacting the CDK2 protein in vivo with the compound.

213. The CDK2 protein of claim 212, wherein the in vivo engineered CDK2 protein is a human in vivo engineered CDK2 protein.

214. The CDK2 protein of any one of claims 204 to 213, wherein the covalent bond between the compound and the lysine residue is a reversible covalent bond.

215. The CDK2 protein of claim 214, wherein the reversible covalent bond in the in vivo CDK2 protein is a carbon-nitrogen double bond.

216. The CDK2 protein of claim 215, wherein the carbon-nitrogen double bond results from a reversible reaction between the amine functional group of K89 and an aldehyde functional group on the compound.

217. The CDK2 protein of claim 216, wherein the aldehyde functional group is an aromatic aldehyde.

218. An in vivo engineered CDK2 protein comprising a non-naturally occurring reversible covalent modification at a lysine residue, the reversible covalent modification being generated from an in vivo nucleophilic reaction between an exogenous aromatic aldehyde and a lysine residue of CDK2, wherein the exogenous aromatic aldehyde undergoes a nucleophilic addition with the amine functional group on the lysine residue and forming a carbon- nitrogen double bond between the exogenous aromatic aldehyde and the amine functional group on the lysine residue.

219. The in vivo engineered CDK2 protein of claim 218, wherein the lysine residue is selected from K6, K9, K20, K24, K33, K34, K56, K65, K88, K89, K105, K129, K142, K178, K237, K242, K250, K273, K278, and K291.

220. The in vivo engineered CDK2 protein of claim 219, wherein the lysine residue is selected from K20, K33, K89, K129, K178, and K278.

221. The in vivo engineered CDK2 protein of claim 219, wherein the lysine is K89.

222. The in vivo engineered CDK2 protein of any one of claim 218 to claim 221, wherein the in vivo engineered CDK2 protein is a human in vivo engineered CDK2 protein.

223. A method of covalently modifying a CDK2 protein, comprising contacting the CDK2 protein with an exogenous CDK2 modulator, wherein the exogenous CDK2 modulator comprises a reversible electrophilic moiety thereby forming a reversible covalent CDK2 adduct.

224. The method of claim 223, wherein the contacting is in vitro.

225. The method of claim 223, wherein the contacting is in vivo.

226. The method of any one of claims 223 to 225, wherein the exogenous CDK2 modulator is an exogenous CDK2 inhibitor.

227. The method of any one of claims 223 to 226, wherein the reversible electrophilic moiety is an aromatic aldehyde.

228. A method of attenuating CDK2 activity, comprising contacting a CDK2 protein with an exogenous CDK2 inhibitor, wherein the exogenous CDK2 inhibitor comprises a reversible electrophilic moiety.

229. The method of claim 228, wherein the contacting is in vitro.

230. The method of claim 229, wherein following the contacting, the CDK2 activity is attenuated by 50% or more relative to a control in the absence of the exogenous CDK2 inhibitor.

231. The method of claim 230, wherein following the contacting, the CDK2 activity is attenuated by 70% or more relative to a control in the absence of the exogenous CDK2 inhibitor.

232. The method of any one of claims 223 to 231, wherein the exogenous CDK2 inhibitor is a compound or salt of claim 1, or a pharmaceutical composition of claim 194.

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