STAT6 modulators and methods of uses thereof

Abstract

The disclosure provides for compounds, compositions, and methods for modulating STAT6.

Description

STAT6 MODULATORS AND METHODS OF USES THEREOFCROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Application Serial No. 63 / 636,633 filed 19-Apr-2024, U.S. Provisional Application Serial No. 63 / 662,078 filed 20-Jun-2024, U.S. Provisional Application Serial No. 63 / 673,537 filed 19-Jul-2024, U.S. Provisional Application Serial No. 63 / 694,665 filed 13-Sep-2024, U.S. Provisional Application Serial No. 63 / 724,224 filed 22-Nov-2024, U.S. Provisional Application Serial No. 63 / 765,019 filed 28-Feb-2025, and U.S. Provisional Application Serial No. 63 / 774,384 filed 19-Mar-2025; which are hereby incorporated by reference in their entirety.BACKGROUND

[0002] The Signal Transducer and Activator of Transcription (STAT) family of proteins consists of transcription factors that play an essential role in the regulation of cell processes, such as proliferation, differentiation, apoptosis and angiogenesis. Seven STAT genes have been identified in the human genome: STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6.

[0003] Activation of STAT6, like other STAT proteins, is triggered upon binding of hormones, immunomodulatory cytokines or growth factors to specific receptors on the cell surface. Once activated, the phosphorylation of a C-terminal tyrosine residue occurs, leading to translocation and transmission of signals from the cytosol to the nucleus, resulting in activation of gene expression.

[0004] STAT6 is implicated in driving Type 2 immunity, allergies. It may participate in IL-4 / IL-13- mediated allergic reaction, and play a vital role in the differentiation of T-helper type 2 (Th2) cells. STAT6 is a key node primarily activated in the Janus Kinase (JAK) pathway by inflammatory cytokines, interleukin-4 (IU4) and interleukin- 13 (IU13) and their cognate receptors, which are produced by Th2 cells, mast cells and basophils. Human STAT6 mutations have been associated with severe allergies such as asthma and eczema. There is a need to discover and develop STAT6 drugs, for example to treat allergic / inflammatory diseases and cancers. As such, small molecules that modulate STAT6 directly to target disease-associated proteins such as STAT6 hold promise as therapeutic agents.SUMMARY

[0005] Disclosed herein is a compound of Formula (IVb), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:as defined herein.

[0006] Disclosed herein is a compound of Formula (IXa), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:as defined herein.

[0007] Disclosed herein is a compound of Formula (IXb), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:as defined herein.

[0008] Also disclosed herein is a pharmaceutical composition comprising a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, and a pharmaceutically acceptable excipient.

[0009] Also disclosed herein is a method of treating a disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, or the pharmaceutical composition disclosed herein.

[0010] In some embodiments, the disorder in alopecia, aspergillus, asthma, atomic dermatitis, chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis with nasal polyposis, gastritis, inflammatory bowel disease, pemphigoid, prurigo nodularis, sinusitis, or urticaria. INCORPORATION BY REFERENCE

[0011] 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. DETAILED DESCRIPTION Definitions

[0012] In the following description, certain specific details are set forth to provide a thorough understanding of various embodiments. However, one skilled in the art will understand that the inventionmay be practiced without these details. In other instances, well-known structures have not been shown or described in detail to avoid unnecessarily obscuring descriptions of the embodiments. Unless the context requires otherwise, throughout the specification and claims which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense, that is, as “including, but not limited to.” Further, headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed invention.

[0013] Reference throughout this specification to “some embodiments” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. Also, as used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. It should also be noted that the term “or” is generally employed in its sense including “and / or” unless the content clearly dictates otherwise.

[0014] The terms below, as used herein, have the following meanings, unless indicated otherwise:

[0015] “Oxo” refers to =O.

[0016] “Amino” refers to -NH2.

[0017] “Hydroxy” refers to -OH.

[0018] “Carboxyl” refers to -COOH.

[0019] “Alkyl” refers to a straight-chain or branched-chain saturated hydrocarbon monoradical having from one to about ten carbon atoms, more preferably one to six carbon atoms. Examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1- butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3- dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, tert-amyl and hexyl, and longer alkyl groups, such as heptyl, octyl and the like. Whenever it appears herein, a numerical range, such as “C1-C6alkyl,” means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkyl” where no numerical range is designated. In some embodiments, the alkyl is a C1-C10alkyl. In some embodiments, the alkyl is a C1-C6alkyl, a C1-C5alkyl, a C1-C4alkyl, or a C1-C3alkyl. Unless stated otherwise specifically in the specification, an alkyl group may be optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the alkyl is independently optionally substituted with one or more oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkyl is independently optionally substituted with one or more halogen, -CN, -OH, or -OMe. In some embodiments, the alkyl is independently optionally substituted with halogen.

[0020] “Alkenyl” refers to a straight-chain or branched-chain hydrocarbon monoradical having one or more carbon-carbon double-bonds and having from two to about ten carbon atoms, more preferably two to about six carbon atoms. The group may be in either the cis or trans or Z or E conformation about the double bond(s) and should be understood to include both isomers. Examples include, but are not limited to, ethenyl (-CH=CH2), 1-propenyl (-CH2CH=CH2), isopropenyl [-C(CH3)=CH2], butenyl, 1,3-butadienyl and the like. Whenever it appears herein, a numerical range, such as “C2-C6alkenyl,” means that the alkenyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkenyl” where no numerical range is designated. Unless stated otherwise specifically in the specification, an alkenyl group may be optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the alkenyl is independently optionally substituted with one or more oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkenyl is independently optionally substituted with one or more halogen, -CN, -OH, or -OMe. In some embodiments, the alkenyl is independently optionally substituted with halogen.

[0021] “Alkynyl” refers to a straight-chain or branched-chain hydrocarbon monoradical having one or more carbon-carbon triple-bonds and having from two to about ten carbon atoms, more preferably from two to about six carbon atoms. Examples include, but are not limited to, ethynyl, 2-propynyl, 2-butynyl, 1,3-butadiynyl and the like. Whenever it appears herein, a numerical range, such as “C2-C6alkynyl,” means that the alkynyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkynyl” where no numerical range is designated. Unless stated otherwise specifically in the specification, an alkynyl group may be optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the alkynyl is independently optionally substituted with one or more oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkynyl is independently optionally substituted with one or more halogen, -CN, -OH, or -OMe. In some embodiments, the alkynyl is independently optionally substituted with halogen.

[0022] “Alkylene” refers to a straight or branched divalent hydrocarbon chain. Unless stated otherwise specifically in the specification, an alkylene group may be optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the alkylene is independently optionally substituted with one or more oxo, halogen, -CN, -COOH, -COOMe, -OH, - OMe, -NH2, or -NO2. In some embodiments, the alkylene is independently optionally substituted with one or more halogen, -CN, -OH, or -OMe. In some embodiments, the alkylene is independently optionally substituted with halogen.

[0023] “Alkoxy” refers to a radical of the formula -Oalkyl where alkyl is defined as above. Unless stated otherwise specifically in the specification, an alkoxy group may be optionally substituted, forexample, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the alkoxy is independently optionally substituted with one or more halogen, -CN, - COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkoxy is independently optionally substituted with one or more halogen, -CN, -OH, or -OMe. In some embodiments, the alkoxy is independently optionally substituted with halogen.

[0024] “Aryl” refers to a radical derived from a hydrocarbon ring system comprising 6 to 30 carbon atoms and at least one aromatic ring. The aryl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with a cycloalkyl or heterocycloalkyl ring, the aryl is bonded through an aromatic ring atom) or bridged ring systems. In some embodiments, the aryl is a 6- to 10-membered aryl. In some embodiments, the aryl is a 6-membered aryl (phenyl). Aryl radicals include, but are not limited to, anthracenyl, naphthyl, phenanthrenyl, azulenyl, phenyl, chrysenyl, fluoranthenyl, fluorenyl, as-indacenyl, s-indacenyl, indanyl, indenyl, phenalenyl, phenanthrenyl, pleiadenyl, pyrenyl, and triphenylenyl. Unless stated otherwise specifically in the specification, an aryl may be optionally substituted, for example, with one or more halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the aryl is independently optionally substituted with one or more halogen, methyl, ethyl, -CN, -COOH, -COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the aryl is independently optionally substituted with one or more halogen, methyl, ethyl, - CN, -CF3, -OH, or -OMe. In some embodiments, the aryl is independently optionally substituted with halogen.

[0025] “Cycloalkyl” refers to a partially or fully saturated, monocyclic, or polycyclic carbocyclic ring, which may include fused (when fused with an aryl or a heteroaryl ring, the cycloalkyl is bonded through a non-aromatic ring atom), spiro, and / or bridged ring systems. In some embodiments, the cycloalkyl is fully saturated. Representative cycloalkyls include, but are not limited to, cycloalkyls having from three to fifteen carbon atoms (e.g., C3-C15fully saturated cycloalkyl or C3-C15cycloalkenyl), from three to ten carbon atoms (e.g., C3-C10fully saturated cycloalkyl or C3-C10cycloalkenyl), from three to eight carbon atoms (e.g., C3-C8fully saturated cycloalkyl or C3-C8cycloalkenyl), from three to six carbon atoms (e.g., C3-C6fully saturated cycloalkyl or C3-C6cycloalkenyl), from three to five carbon atoms (e.g., C3-C5fully saturated cycloalkyl or C3-C5cycloalkenyl), or three to four carbon atoms (e.g., C3-C4fully saturated cycloalkyl or C3-C4cycloalkenyl). In some embodiments, the cycloalkyl is a 3- to 10-membered fully saturated cycloalkyl or a 3- to 10-membered cycloalkenyl. In some embodiments, the cycloalkyl is a 3- to 6-membered fully saturated cycloalkyl or a 3- to 6-membered cycloalkenyl. In some embodiments, the cycloalkyl is a 5- to 6-membered fully saturated cycloalkyl or a 5- to 6-membered cycloalkenyl. Monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyls include, for example, adamantyl, norbornyl, decalinyl, bicyclo[3.3.0]octyl, bicyclo[4.3.0]nonyl, cis-decalinyl, trans-decalinyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[3.2.1]octyl, bicyclo[3.2.2]nonyl, andbicyclo[3.3.2]decyl, bicyclo[1.1.1]pentyl, bicyclo[3.1.0]hexyl, bicyclo[3.1.1]heptyl, 7,7-dimethyl- bicyclo[2.2.1]heptanyl, spiro[4.2]heptyl, spiro[4.3]octyl, spiro[5.2]octyl, spiro[3.3]heptyl, and spiro[5.3]nonyl. Partially saturated cycloalkyls include, for example cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Unless stated otherwise specifically in the specification, a cycloalkyl is independently optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, a cycloalkyl is independently optionally substituted with one or more oxo, halogen, methyl, ethyl, -CN, -COOH, -COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, a cycloalkyl is independently optionally substituted with one or more oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the cycloalkyl is independently optionally substituted with halogen.

[0026] “Halo” or “halogen” refers to bromo, chloro, fluoro or iodo. In some embodiments, halogen is fluoro or chloro. In some embodiments, halogen is fluoro. In some embodiments, halogen is chloro.

[0027] “Haloalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more halo radicals, as defined above, e.g., trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 2,2,2- trifluoroethyl, 1,2-difluoroethyl, 2-fluoroethyl, 3-bromo-2-fluoropropyl, 1,2-dibromoethyl, and the like.

[0028] “Haloalkoxy” refers to -O-haloalkyl, with haloalkyl as defined above.

[0029] “Hydroxyalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more hydroxyls. In some embodiments, the alkyl is substituted with one hydroxyl. In some embodiments, the alkyl is substituted with one, two, or three hydroxyls. Hydroxyalkyl includes, for example, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, or hydroxypentyl. In some embodiments, the hydroxyalkyl is hydroxymethyl.

[0030] “Aminoalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more amines. In some embodiments, the alkyl is substituted with one amine. In some embodiments, the alkyl is substituted with one, two, or three amines. Aminoalkyl includes, for example, aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the aminoalkyl is aminomethyl.

[0031] “Heteroalkyl” refers to an alkyl group in which one or more skeletal atoms of the alkyl are selected from an atom other than carbon, e.g., oxygen, nitrogen, sulfur, phosphorus, or combinations thereof. A heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl. In one aspect, a heteroalkyl is a C1-C6heteroalkyl wherein the heteroalkyl is comprised of 1 to 6 carbon atoms and one or more atoms other than carbon, e.g., oxygen, nitrogen, sulfur, phosphorus, or combinations thereof wherein the heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl. In one aspect, a heteroalkyl is a C1-C6heteroalkyl wherein the heteroalkyl is comprised of 1 to 6 carbon atoms and one or two atoms selected from the group consisting of oxygen, nitrogen, and sulfur wherein the heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl. Examples of such heteroalkyl are, for example, -CH2OCH3, -CH2CH2OCH3, -CH2CH2OCH2CH2OCH3, - CH(CH3)OCH3, -CH2NHCH3, -CH2N(CH3)2, -CH2CH2NHCH3, or -CH2CH2N(CH3)2. Unless stated otherwise specifically in the specification, a heteroalkyl is independently optionally substituted forexample, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, a heteroalkyl is independently optionally substituted with one or more oxo, halogen, methyl, ethyl, -CN, - CF3, OH, -OMe, NH2, or -NO2. In some embodiments, a heteroalkyl is independently optionally substituted with one or more oxo, halogen, methyl, ethyl, -CN, -CF3, OH, or -OMe. In some embodiments, the heteroalkyl is independently optionally substituted with halogen.

[0032] “Heterocycloalkyl” refers to a 3- to 24-membered partially or fully saturated ring radical comprising 2 to 23 carbon atoms and from one to 8 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorous, silicon, and sulfur. In some embodiments, the heterocycloalkyl is a 3- to 8-membered partially or fully saturated ring comprising one, two, or three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heterocycloalkyl is a 3- to 6- membered partially or fully saturated ring comprising one or two heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heterocycloalkyl is a 3- to 6- membered fully saturated ring comprising one or two heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heterocycloalkyl is fully saturated. In some embodiments, the heterocycloalkyl is C-linked. In some embodiments, the heterocycloalkyl is N-linked. In some embodiments, the heterocycloalkyl comprises one to three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heterocycloalkyl comprises one to three heteroatoms selected from the group consisting of nitrogen and oxygen. In some embodiments, the heterocycloalkyl comprises one to three nitrogens. In some embodiments, the heterocycloalkyl comprises one or two nitrogens. In some embodiments, the heterocycloalkyl comprises one nitrogen. In some embodiments, the heterocycloalkyl comprises one nitrogen and one oxygen. Unless stated otherwise specifically in the specification, the heterocycloalkyl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with an aryl or a heteroaryl ring, the heterocycloalkyl is bonded through a non-aromatic ring atom), spiro, or bridged ring systems; and the nitrogen, carbon, or sulfur atoms in the heterocycloalkyl radical may be optionally oxidized; the nitrogen atom may be optionally quaternized. Representative heterocycloalkyls include, but are not limited to, heterocycloalkyls having from two to fifteen carbon atoms (e.g., C2-C15fully saturated heterocycloalkyl or C2-C15heterocycloalkenyl), from two to ten carbon atoms (e.g., C2-C10fully saturated heterocycloalkyl or C2-C10 heterocycloalkenyl), from two to eight carbon atoms (e.g., C2-C8 fully saturated heterocycloalkyl or C2-C8heterocycloalkenyl), from two to seven carbon atoms (e.g., C2-C7fully saturated heterocycloalkyl or C2-C7 heterocycloalkenyl), from two to six carbon atoms (e.g., C2-C6fully saturated heterocycloalkyl or C2-C7 heterocycloalkenyl), from two to five carbon atoms (e.g., C2-C5fully saturated heterocycloalkyl or C2-C5heterocycloalkenyl), or two to four carbon atoms (e.g., C2-C4fully saturated heterocycloalkyl or C2-C4heterocycloalkenyl). Examples of such heterocycloalkyl radicals include, but are not limited to, aziridinyl, azetidinyl, oxetanyl, 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, 1,1-dioxo-thiomorpholinyl, 1,3-dihydroisobenzofuran-1-yl, 3-oxo-1,3- dihydroisobenzofuran-1-yl, methyl-2-oxo-1,3-dioxol-4-yl, and 2-oxo-1,3-dioxol-4-yl. The term heterocycloalkyl also includes all ring forms of the carbohydrates, including but not limited to the monosaccharides, the disaccharides, and the oligosaccharides. In some embodiments, heterocycloalkyls have from 2 to 10 carbons in the ring. It is understood that when referring to the number of carbon atoms in a heterocycloalkyl, the number of carbon atoms in the heterocycloalkyl is not the same as the total number of atoms (including the heteroatoms) that make up the heterocycloalkyl (i.e., skeletal atoms of the heterocycloalkyl ring). In some embodiments, the heterocycloalkyl is a 3- to 8-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 3- to 7-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 3- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 4- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 5- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 3- to 8- membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 3- to 7-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 3- to 6-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 4- to 6-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 5- to 6-membered heterocycloalkenyl. Unless stated otherwise specifically in the specification, a heterocycloalkyl is independently optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, the heterocycloalkyl is independently optionally substituted with one or more oxo, halogen, methyl, ethyl, -CN, -COOH, -COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the heterocycloalkyl is independently optionally substituted with one or more halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heterocycloalkyl is independently optionally substituted with halogen.

[0033] “Heteroaryl” refers to a 5- to 14-membered ring system radical comprising one to thirteen carbon atoms, one to six heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorous, and sulfur, and at least one aromatic ring. In some embodiments, the heteroaryl is a 5- to 10-membered ring comprising one, two, or three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heteroaryl is a 5- to 6-membered ring comprising one or two heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heteroaryl comprises one to three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heteroaryl comprises one to three heteroatoms selected from the group consisting of nitrogen and oxygen. In some embodiments, the heteroaryl comprises one to three nitrogens. In some embodiments, the heteroaryl comprises one or two nitrogens. In some embodiments, the heteroaryl comprises one nitrogen. In some embodiments, the heteroaryl is C-linked. In some embodiments, the heteroaryl is N-linked. The heteroaryl radical may be a monocyclic, bicyclic, tricyclic,or tetracyclic ring system, which may include fused (when fused with a cycloalkyl or heterocycloalkyl ring, the heteroaryl is bonded through an aromatic ring atom) or bridged ring systems; and the nitrogen, carbon, or sulfur atoms in the heteroaryl radical may be optionally oxidized; the nitrogen atom may be optionally quaternized. In some embodiments, the heteroaryl is a 5- to 10-membered heteroaryl comprising 1, 2, or 3 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. In some embodiments, the heteroaryl is a 5- to 6-membered heteroaryl comprising 1, 2, or 3 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. In some embodiments, the heteroaryl is a 6-membered heteroaryl comprising 1, 2, or 3 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. In some embodiments, the heteroaryl is a 5-membered heteroaryl comprising 1, 2, or 3 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. Examples include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, isothiazolyl, imidazolyl, indazolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, 1-oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl, 1- oxidopyridazinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e., thienyl). Unless stated otherwise specifically in the specification, a heteroaryl is independently optionally substituted, for example, with one or more halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the heteroaryl is independently optionally substituted with one or more halogen, methyl, ethyl, -CN, -COOH, -COOMe, -CF3, -OH, - OMe, -NH2, or -NO2. In some embodiments, the heteroaryl is independently optionally substituted with one or more halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heteroaryl is independently optionally substituted with halogen.

[0034] The term “optional” or “optionally” means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances in which it does not. For example, “optionally substituted alkyl” means either “alkyl” or “substituted alkyl” as defined above. Further, an optionally substituted group may be un- substituted (e.g., -CH2CH3), fully substituted (e.g., -CF2CF3), mono-substituted (e.g., -CH2CH2F) or substituted at a level anywhere in-between fully substituted and mono-substituted (e.g., -CH2CHF2, - CH2CF3, -CF2CH3, -CFHCHF2, etc.).

[0035] The term “one or more” when referring to an optional substituent means that the subject group is independently optionally substituted with one, two, three, or four, or more substituents. In some embodiments, the subject group is independently optionally substituted with one, two, three, or foursubstituents. In some embodiments, the subject group is independently optionally substituted with one, two, or three substituents. In some embodiments, the subject group is independently optionally substituted with one or two substituents. In some embodiments, the subject group is independently optionally substituted with one substituent. In some embodiments, the subject group is independently optionally substituted with two substituents. In some embodiments, the subject group is independently optionally substituted with three substituents.

[0036] An “effective amount” or “therapeutically effective amount” refers to an amount of a compound administered to a mammalian subject, either as a single dose or as part of a series of doses, which is effective to produce a desired therapeutic effect.

[0037] “Treatment” of an individual (e.g., a mammal, such as a human) or a cell is any type of intervention used in an attempt to alter the natural course of the individual or cell. In some embodiments, treatment includes administration of a pharmaceutical composition subsequent to the initiation of a pathologic event or contact with an etiologic agent and includes stabilization of the condition (e.g., condition does not worsen) or alleviation of the condition.

[0038] “Synergy” or “synergize” refers to an effect of a combination that is greater than additive of the effects of each component alone at the same doses.

[0039] As used herein, a “disease or disorder associated with STAT6” or, alternatively, “a STAT6- mediated disease or disorder” means any disease or other deleterious condition in which STAT6, or a mutant thereof, is known or suspected to play a role. Compounds

[0040] Described herein are compounds, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, useful in the treatment of a disease or disorder associated with STAT6.

[0041] Disclosed herein is a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R20is -L-NR10 11 12 13 11 10 11C(=O)R , -L-C(=O)NR R , -L-S(=O)2R , -L-S(=O)(=NR )R , or - L-P(=O)(R11)2; Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;each R1is independently halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, - S(=O)2NRcRd, -NRcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L- heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; and / or two R1on the same carbon atom are taken together to form an oxo; n is 0, 1, 2, 3, 4, 5, or 6; R10is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl; R11is C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R12and R13are independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R12and R13are taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; U is N and T is C; or U is C and T is N; Y1is N or CR3; R3is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SF5, -SH, - SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, - NRbC(=O)ORb, -NRbS(=O)2Ra, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Y2is N or CR4; R4is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; whereineach alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X1is N or CR5; R5is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X2is N or CR6; R6is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R5and R6are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; X3is N or CR7; R7is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R6and R7are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; and / or two R on the same atom form an oxo; provided that the compound is not:

[0042] In some embodiments of a compound of Formula (I), U is N and T is C. In some embodiments of a compound of Formula (I), U is C and T is N.

[0043] In some embodiments of a compound of Formula (I), Y1is N. In some embodiments of a compound of Formula (I), Y1is CR3.

[0044] In some embodiments of a compound of Formula (I), Y2is N. In some embodiments of a compound of Formula (I), Y2is CR4.

[0045] In some embodiments of a compound of Formula (I), X1is N. In some embodiments of a compound of Formula (I), X1is CR5.

[0046] In some embodiments of a compound of Formula (I), X2is N. In some embodiments of a compound of Formula (I), X2is CR6.

[0047] In some embodiments of a compound of Formula (I), X3is N. In some embodiments of a compound of Formula (I), X3is CR7.

[0048] In some embodiments of a compound of Formula (I),

[0049] In some embodiments of a compound of Formula (I),

[0050] In some embodiments of a compound of Formula (I),.

[0051] In some embodiments of a compound of Formula (I),.

[0052] In some embodiments of a compound of Formula (I),

[0053] In some embodiments of a compound of Formula (I),

[0054] In some embodiments of a compound of Formula (I),

[0055] In some embodiments of a compound of Formula (I),

[0056] In some embodiments of a compound of Formula (I),

[0057] In some embodiments of a compound of Formula (I), R3is hydrogen, halogen, -CN, -OH, -ORa, - NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, -L- cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl, heteroalkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R.

[0058] In some embodiments of a compound of Formula (I), R3is hydrogen, -OH, -ORa, C1-C6alkyl, C1- C6haloalkyl, C1-C6heteroalkyl, or -L-cycloalkyl; wherein each alkyl, heteroalkyl, and cycloalkyl is independently optionally substituted with one or more R.

[0059] In some embodiments of a compound of Formula (I), R3is -ORa, C1-C6alkyl, C1-C6heteroalkyl, or -L-cycloalkyl; wherein each alkyl, heteroalkyl, and cycloalkyl is independently optionally substituted with one or more R.

[0060] In some embodiments of a compound of Formula (I), R3is C1-C6alkyl.

[0061] Also disclosed herein is a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R20is -L-NR10C(=O)R11, -L-C(=O)NR12R13, -L-11 10 11S(=O)2R , -L-S(=O)(=NR )R , or - L-P(=O)(R11)2; Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R1is independently halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, - S(=O)2NRcRd, -NRcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L- heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;and / or two R1on the same carbon atom are taken together to form an oxo; n is 0, 1, 2, 3, 4, 5, or 6; R10is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl; R11is C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R12and R13are independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R12and R13are taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Y1is NRY1, CR3, N, O, or S; R3is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SF5, -SH, - SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, - NRbC(=O)ORb, -NRbS(=O)2Ra, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Y2is NRY2, CR4, N, O, or S; R4is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;RY2is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Y3is N or C; (i) provided that when Y2is N then Y1is not NRY1unless at least one of X1, X2, and X3is N and / or at least two Zs are N but provided thatis not; and / or (ii) provided that when Y2is CR4then Y1is not NRY1unless at least two of X1, X2, and X3is N and / or unless at least two Zs are N; X1is N or CR5; R5is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X2is N or CR6; R6is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R5and R6are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; X3is N or CR7; R7is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R6and R7are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; Ring B is phenyl or 5- or 6-membered heteroaryl; each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl,heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; and / or two R8on adjacent atoms are taken together to form a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; and L is absent or C1-C3alkylene independently optionally substituted with one or more R; each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein the cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more halogen, -CN, -OH, - NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, or C1-C3heteroalkyl; and / or two R on the same atom form an oxo.

[0062] In some embodiments of a compound of Formula (II), Y1is NRY1. In some embodiments of a compound of Formula (II), Y1is CR3.

[0063] In some embodiments of a compound of Formula (II), Y2is NRY2. In some embodiments of a compound of Formula (II), Y2is CR4. In some embodiments of a compound of Formula (II), Y2is N. In some embodiments of a compound of Formula (II), Y2is O. In some embodiments of a compound of Formula (II), Y2is S.

[0064] In some embodiments of a compound of Formula (II), Y2is not N and Y1is not NRY1.

[0065] In some embodiments of a compound of Formula (II), Y2is not CR4and Y1is not NRY1.

[0066] In some embodiments of a compound of Formula (II), Y3is N. In some embodiments of a compound of Formula (II), Y3is C.

[0067] In some embodiments, the compound of Formula (II) is:

[0068] In some embodiments, the compound of Formula (II) is:

[0069] In some embodiments of a compound of Formula (II), X1is N. In some embodiments of a compound of Formula (II), X1is CR5.

[0070] In some embodiments of a compound of Formula (II), X2is N. In some embodiments of a compound of Formula (II), X2is CR6.

[0071] In some embodiments of a compound of Formula (II), X3is N. In some embodiments of a compound of Formula (II), X3is CR7.

[0072] In some embodiments of a compound of Formula (II),In some embodiments of a compound of Formula

[0073] In some embodiments of a compound of Formula (II),

[0074] In some embodiments of a compound of Formula (II),

[0075] In some embodiments of a compound of Formula (II),

[0076] In some embodiments of a compound of Formula (II),

[0077] In some embodiments of a compound of Formula (II),.

[0078] In some embodiments of a compound of Formula (II),

[0079] In some embodiments of a compound of Formula (II),

[0080] In some embodiments of a compound of Formula (II),

[0081] In some embodiments of a compound of Formula (II),

[0082] In some embodiments of a compound of Formula (II),In some embodiments of a compound of Formula (II),

[0083] In some embodiments of a compound of Formula (II),

[0084] In some embodiments of a compound of Formula (II),In some embodiments of a compound of Formula (II),

[0085] In some embodiments of a compound of Formula (I) or (II), R3is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, -L- cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl, heteroalkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I) or (II), R3is hydrogen, -OH, -ORa, C1-C6alkyl, C1-C6haloalkyl, C1-C6heteroalkyl, or -L- cycloalkyl; wherein each alkyl, heteroalkyl, and cycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I) or (II), R3is -ORa, C1-C6alkyl, C1- C6heteroalkyl, or -L-cycloalkyl; wherein each alkyl, heteroalkyl, and cycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I) or (II), R3is C1-C6alkyl. In some embodiments of a compound of Formula (I) or (II), R3is hydrogen.

[0086] In some embodiments of a compound of Formula (I) or (II), R4is hydrogen, halogen, -CN, -OH, -ORa, C1-C6alkyl, C1-C6haloalkyl, C1-C6heteroalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (I) or (II), R4is hydrogen, halogen, C1-C6alkyl, C1-C6haloalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (I) or (II), R4is hydrogen, halogen, or C1-C6alkyl. In some embodiments of a compound of Formula (I) or (II), R4is hydrogen or C1- C6alkyl. In some embodiments of a compound of Formula (I) or (II), R4is hydrogen or halogen. In someembodiments of a compound of Formula (I) or (II), R4is hydrogen. In some embodiments of a compound of Formula (I) or (II), R4is hydrogen or C1-C6alkyl.

[0087] In some embodiments of a compound of Formula (I) or (II), R5is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (I) or (II), R5is hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (I) or (II), R5is hydrogen.

[0088] In some embodiments of a compound of Formula (I) or (II), R6is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (I) or (II), R6is hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (I) or (II), R6is hydrogen, halogen, or C1-C6haloalkyl.

[0089] In some embodiments of a compound of Formula (I) or (II), R6is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (I) or (II), R6is hydrogen, halogen, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (I) or (II), R6is hydrogen, -NRcRd, C1-C6alkyl, C1- C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (I) or (II), R6is hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (I) or (II), R6is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (I) or (II), R6is C1- C6haloalkyl. In some embodiments of a compound of Formula (I) or (II), R6is C1-C6alkyl. In some embodiments of a compound of Formula (I) or (II), R6is halogen or C1-C6haloalkyl. In some embodiments of a compound of Formula (I) or (II), R6is C1-C6alkyl or C1-C6haloalkyl.

[0090] In some embodiments of a compound of Formula (I) or (II), R7is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (I) or (II), R7is hydrogen, halogen, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (I) or (II), R7is hydrogen, halogen, C1-C6alkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (I) or (II), R7is hydrogen, halogen, or C1-C6alkyl. In some embodiments of a compound of Formula (I) or (II), R7is hydrogen.

[0091] In some embodiments of a compound of Formula (I) or (II), R7is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (I) or (II), R7is hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (I) or (II), R7is C1-C6haloalkyl.

[0092] In some embodiments of a compound of Formula (II), RY1is hydrogen, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (II), RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (II), RY1is hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (II), RY1is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (II), RY1is hydrogen. In some embodiments of a compound of Formula (II), RY1is C1-C6alkyl independently optionally substituted with one or more R. In some embodiments of a compound of Formula (II), RY1is C1-C6alkyl. In some embodiments of a compound of Formula (II), RY1is ethyl. In some embodiments of a compound of Formula (II), one or more hydrogen in RY1is replaced with a deuterium atom. In some embodiments of a compound of Formula (II), RY1is -CD2CD3or - CH2CH2OCD3. In some embodiments of a compound of Formula (II), RY1is -CD2CD3. In some embodiments of a compound of Formula (II), RY1is -CH2CH2OCD3.

[0093] In some embodiments of a compound of Formula (II), RY2is hydrogen, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (II), RY2is hydrogen, C1-C6alkyl, C1-C6haloalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (II), RY2is hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (II), RY2is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (II), RY2is hydrogen. In some embodiments of a compound of Formula (II), RY2is C1-C6alkyl.

[0094] In some embodiments of a compound of Formula (I) or (II),In( )

[0095] In some embodiments of a compound of Formula (I) or (II),

[0096] In some embodiments of a compound of Formula (I) or (II), each R2is independently hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1- C6heteroalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (I) or (II), each R2is independently hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (I) or (II), each R2is independently hydrogen, halogen, -CN, -OH, -ORa, C1- C6alkyl, or -L-cycloalkyl. In some embodiments of a compound of Formula (I) or (II), each R2is independently hydrogen, halogen, -CN, -ORa, or -L-cycloalkyl. In some embodiments of a compound of Formula (I) or (II), each R2is independently hydrogen, halogen, or -ORa. In some embodiments of a compound of Formula (I) or (II), each R2is independently hydrogen or -ORa. In some embodiments of a compound of Formula (I) or (II), each R2is independently hydrogen, halogen, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (I) or (II), each R2is independently hydrogen, halogen, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (I) or (II), each R2is independently hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (I) or (II), each R2is independently hydrogen or halogen. In some embodiments of a compound of Formula (I) or (II), each R2is hydrogen.

[0097] In some embodiments of a compound of Formula (I) or (II), R20is.

[0098] In some embodiments of a compound of Formula (I) or (II), Ring A is heterocycloalkyl. In some embodiments of a compound of Formula (I) or (II), Ring A is 5- or 6-membered heterocycloalkyl. In some embodiments of a compound of Formula (I) or (II), Ring A is 5-membered heterocycloalkyl. In some embodiments of a compound of Formula (I) or (II), Ring A is 6-membered heterocycloalkyl.

[0099] In some embodiments of a compound of Formula (I) or (II), each R1is independently halogen, - CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1- C6heteroalkyl; and / or two R1on the same carbon atom are taken together to form an oxo.

[0100] In some embodiments of a compound of Formula (I) or (II), each R1is independently C1-C6alkyl; and / or two R1on the same carbon atom are taken together to form an oxo.

[0101] In some embodiments of a compound of Formula (I) or (II), n is 2, 3, or 4. In some embodiments of a compound of Formula (I) or (II), n is 3 or 4. In some embodiments of a compound of Formula (I) or (II), n is 2. In some embodiments of a compound of Formula (I) or (II), n is 3. In some embodiments of a compound of Formula (I) or (II), n is 4.

[0102] In some embodiments of a compound of Formula (I) or (II),wherein:R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R31is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X is -O-, -S-, -NR32-, or -C(R33)2-; R32is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each R33is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R.

[0103] In some embodiments of a compound of Formula (I) or (II), R30is hydrogen, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L- cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl. In some embodiments of a compound of Formula (I) or (II), R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, -L-cycloalkyl, or -L- heterocycloalkyl. In some embodiments of a compound of Formula (I) or (II), R30is hydrogen, C1- C6alkyl, or -L-cycloalkyl. In some embodiments of a compound of Formula (I) or (II), R30is C1-C6alkyl or -L-cycloalkyl. In some embodiments of a compound of Formula (I) or (II), R30is C1-C6alkyl.

[0104] In some embodiments of a compound of Formula (I) or (II), R30is -CH3. In some embodiments of a compound of Formula (I) or (II), R30is -CD3.

[0105] In some embodiments of a compound of Formula (I) or (II), R31is hydrogen, halogen, -CN, - NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1- C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl. In some embodiments of a compound of Formula (I) or (II), R31is hydrogen, halogen, - CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, -L-cycloalkyl, or -L- heterocycloalkyl.

[0106] In some embodiments of a compound of Formula (I) or (II), R31is hydrogen, -CN, C1-C6alkyl, C1-C6hydroxyalkyl, or -L-cycloalkyl. In some embodiments of a compound of Formula (I) or (II), R31is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (I) or (II), R31is C1-C6alkyl.

[0107] In some embodiments of a compound of Formula (I) or (II), X is -O-. In some embodiments of a compound of Formula (I) or (II), X is -S-. In some embodiments of a compound of Formula (I) or (II), X is -NR32-. In some embodiments of a compound of Formula (I) or (II), X is -C(R33)2-.

[0108] In some embodiments of a compound of Formula (I) or (II), R32is hydrogen, C1-C6alkyl, or C1- C6haloalkyl. In some embodiments of a compound of Formula (I) or (II), R32is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (I) or (II), R32is hydrogen. In some embodiments of a compound of Formula (I) or (II), R32is C1-C6alkyl. In some embodiments of a compound of Formula (I) or (II), each R33is independently hydrogen, halogen, -OH, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (I) or (II), each R33is independently hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (I) or (II), each R33is hydrogen.

[0109] In some embodiments of a compound of Formula (I) or (II),

[0110] In some embodiments of a compound of Formula (I) or (II),or

[0111] In some embodiments of a compound of Formula (I) or (II),, , , ,

[0112] In some embodiments of a compound of Formula (I) or (II),orIn some embodiments of a compound of Formula (I) or (II),is

[0113] In some embodiments of a compound of Formula (I) or (II), R20is -NR10C(=O)R11.

[0114] In some embodiments of a compound of Formula (I) or (II), R20is -L-S(=O)2R11, -L- S(=O)(=NR10)R11, or -L-P(=O)(R11)2.

[0115] In some embodiments of a compound of Formula (I) or (II), R20is -L-S(=O)2R11.

[0116] In some embodiments of a compound of Formula (I) or (II), R20is -S(=O)2R11. In some embodiments of a compound of Formula (I) or (II), R20is -CH2-S(=O)2R11.

[0117] In some embodiments of a compound of Formula (I) or (II), R20is -L-S(=O)(=NR10)R11. In some embodiments of a compound of Formula (I) or (II), R20is -S(=O)(=NR10)R11. In some embodiments of a compound of Formula (I) or (II), R20is -CH2-S(=O)(=NR10)R11.

[0118] In some embodiments of a compound of Formula (I) or (II), R20is -L-P(=O)(R11)2. In some embodiments of a compound of Formula (I) or (II), R20is -P(=O)(R11)2. In some embodiments of a compound of Formula (I) or (II), R20is -CH2-P(=O)(R11)2.

[0119] In some embodiments of a compound of Formula (I) or (II), R10is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (I) or (II), R10is C1-C6alkyl. In some embodiments of a compound of Formula (I) or (II), R10is hydrogen.

[0120] In some embodiments of a compound of Formula (I) or (II), R11is C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (I) or (II), R11is C1-C6alkyl.

[0121] In some embodiments of a compound of Formula (I) or (II), R20is -C(=O)NR12R13.

[0122] In some embodiments of a compound of Formula (I) or (II), R12and R13are independently hydrogen or C1-C6alkyl.

[0123] Disclosed herein is a compound of Formula (IV), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R20is -L-S(=O)2R11, -L-S(10 11 11=O)(=NR )R , or -L-P(=O)(R )2; R10is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl; R11is C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R31is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X is -O-, -S-, -NR32-, or -C(R33)2-;R32is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each R33is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; U is C or N; T is C or N; provided that not both of U and T are N; Y1is NRY1, CR3, N, O, or S; R3is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SF5, -SH, - SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, - NRbC(=O)ORb, -NRbS(=O)2Ra, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Y2is NRY2, CR4, N, O, or S; R4is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY2is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein thealkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Y3is N or C; X1is N or CR5; R5is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X2is N or CR6; R6is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R5and R6are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; X3is N or CR7; R7is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R6and R7are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein the cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more halogen, -CN, -OH, - NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, or C1-C3heteroalkyl; and / or two R on the same atom form an oxo.

[0124] In some embodiments of a compound of Formula (IV), R20is-L- S(=O)2R11, -L-S(=O)(=NR10)R11, or -L-P(=O)(R11)2.

[0125] In some embodiments of a compound of Formula (IV), R20is-L- S(=O)2R11, -L-S(=O)(=NR10)R11, or -L-P(=O)(R11)2.

[0126] In some embodiments of a compound of Formula (IV), R20is

[0127] In some embodiments of a compound of Formula (IV), R30is hydrogen, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L- cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl. In some embodiments of a compound of Formula (IV), R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, -L-cycloalkyl, or -L- heterocycloalkyl. In some embodiments of a compound of Formula (IV), R30is hydrogen, C1-C6alkyl, or-L-cycloalkyl. In some embodiments of a compound of Formula (IV), R30is C1-C6alkyl or -L-cycloalkyl. In some embodiments of a compound of Formula (IV), R30is C1-C6alkyl.

[0128] In some embodiments of a compound of Formula (IV), R30is -CH3. In some embodiments of a compound of Formula (IV), R30is -CD3.

[0129] In some embodiments of a compound of Formula (IV), R31is hydrogen, halogen, -CN, -NO2, - OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl. In some embodiments of a compound of Formula (IV), R31is hydrogen, halogen, -CN, -OH, - ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, -L-cycloalkyl, or -L-heterocycloalkyl.

[0130] In some embodiments of a compound of Formula (IV), R31is hydrogen, -CN, C1-C6alkyl, C1- C6hydroxyalkyl, or -L-cycloalkyl. In some embodiments of a compound of Formula (IV), R31is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IV), R31is C1-C6alkyl.

[0131] In some embodiments of a compound of Formula (IV), X is -O-. In some embodiments of a compound of Formula (IV), X is -S-. In some embodiments of a compound of Formula (IV), X is -NR32-. In some embodiments of a compound of Formula (IV), X is -C(R33)2-.

[0132] In some embodiments of a compound of Formula (IV), R32is hydrogen, C1-C6alkyl, or C1- C6haloalkyl. In some embodiments of a compound of Formula (IV), R32is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IV), R32is hydrogen. In some embodiments of a compound of Formula (IV), R32is C1-C6alkyl. In some embodiments of a compound of Formula (IV), each R33is independently hydrogen, halogen, -OH, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IV), each R33is independently hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IV), each R33is hydrogen.

[0133] In some embodiments of a compound of Formula (IV), R20isIn some embodiments of a compound of Formula (IV), R20isIn some embodiments of a compound of Formula (IV), R20is

[0134] In some embodiments of a compound of Formula (IV), R20is

[0135] In some embodiments of a compound of Formula (IV), R20is -L-S(=O)2R11, -L- S(=O)(=NR10)R11, or -L-P(=O)(R11)2.

[0136] In some embodiments of a compound of Formula (IV), R20is -L-S(=O)2R11.

[0137] In some embodiments of a compound of Formula (IV), R20is -S(=O)2R11. In some embodiments of a compound of Formula (IV), R20is -CH2-S(=O)2R11.

[0138] In some embodiments of a compound of Formula (IV), R20is -L-S(=O)(=NR10)R11. In some embodiments of a compound of Formula (IV), R20is -S(=O)(=NR10)R11. In some embodiments of a compound of Formula (IV), R20is -CH2-S(=O)(=NR10)R11.

[0139] In some embodiments of a compound of Formula (IV), R20is -L-P(=O)(R11)2. In some embodiments of a compound of Formula (IV), R20is -P(=O)(R11)2. In some embodiments of a compound of Formula (IV), R20is -CH2-P(=O)(R11)2.

[0140] In some embodiments of a compound of Formula (IV), R10is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IV), R10is C1-C6alkyl. In some embodiments of a compound of Formula (IV), R10is hydrogen.

[0141] In some embodiments of a compound of Formula (IV), R11is C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (IV), R11is C1-C6alkyl.

[0142] In some embodiments, the compound of Formula (IV) is a compound of Formula (IVa), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R31is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X is -O-, -S-, -NR32-, or -C(R33)2-; R32is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each R33is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;R4is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R6is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R7is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R6and R7are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein the cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more halogen, -CN, -OH, - NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, or C1-C3heteroalkyl; and / or two R on the same atom form an oxo.

[0143] In some embodiments, the compound of Formula (IV) is a compound of Formula (IVb), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R31is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X is -O-, -S-, -NR32-, or -C(R33)2-; R32is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each R33is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R4is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R6is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X3is N or CR7; R7is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R6and R7are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl,heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein the cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more halogen, -CN, -OH, - NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, or C1-C3heteroalkyl; and / or two R on the same atom form an oxo.

[0144] In some embodiments of a compound of Formula (IVa) or (IVb), R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R30is hydrogen, C1-C6alkyl, or -L-cycloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R30is C1-C6alkyl or -L-cycloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R30is C1-C6alkyl.

[0145] In some embodiments of a compound of Formula (IVa) or (IVb), R30is -CH3. In some embodiments of a compound of Formula (IVa) or (IVb), R30is -CD3.

[0146] In some embodiments of a compound of Formula (IVa) or (IVb), R31is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, -L-cycloalkyl, or -L- heterocycloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R31is hydrogen, -CN, C1-C6alkyl, C1-C6hydroxyalkyl, or -L-cycloalkyl. In some embodiments of a compound of Formula (IVa)or (IVb), R31is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R31is -CN or C1-C6alkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R31is C1- C6alkyl.

[0147] In some embodiments of a compound of Formula (IVa) or (IVb), X is -O-. In some embodiments of a compound of Formula (IVa) or (IVb), X is -S-. In some embodiments of a compound of Formula (IVa) or (IVb), X is -NR32-. In some embodiments of a compound of Formula (IVa) or (IVb), X is - C(R33)2-.

[0148] In some embodiments of a compound of Formula (IVa) or (IVb), R32is hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R32is hydrogen or C1- C6alkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R32is hydrogen. In some embodiments of a compound of Formula (IVa) or (IVb), R32is C1-C6alkyl. In some embodiments of a compound of Formula (IVa) or (IVb), each R33is independently hydrogen, halogen, -OH, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), each R33is independently hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IVa) or (IVb), each R33is hydrogen.

[0149] In some embodiments of a compound of Formula (IVa) or (IVb),

[0150] In some embodiments, the compound of Formula (IVa) or (IVb) has the following formula:.

[0151] In some embodiments, the compound of Formula (IVa) or (IVb) has the following formula:.

[0152] In some embodiments, the compound of Formula (IVb) has the following formula:.

[0153] In some embodiments of a compound of Formula (IVa) or (IVb), each Z is independently CR2. In some embodiments of a compound of Formula (IVa) or (IVb), one Z is N and the remaining Z are independently CR2.

[0154] In some embodiments of a compound of Formula (IVa) or (IVb),

[0155] In some embodiments of a compound of Formula (IVa) or (IVb),.

[0156] In some embodiments of a compound of Formula (IVa) or (IVb),or In some embodiments of a compound of Formula (IVa) or (IVb), is . In some embodiments of a compound of Formula (IVa) or (IVb),is.

[0157] In some embodiments, the compound of Formula (IVa) or (IVb) has the following formula:.

[0158] In some embodiments, the compound of Formula (IVa) or (IVb) has the following formula:.

[0159] In some embodiments, the compound of Formula (IVb) has the following formula:.

[0160] In some embodiments, the compound of Formula (IVa) or (IVb) has the following formula:In some embodiments, the compound of Formula (IVa) or (IVb) has the following formula:

[0161] In some embodiments of a compound of Formula (IVa) or (IVb), each R2is independently hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1- C6aminoalkyl, C1-C6heteroalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), each R2is independently hydrogen, halogen, -CN, -OH, -ORa, - NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), each R2is independently hydrogen, halogen, - CN, -OH, -ORa, C1-C6alkyl, or -L-cycloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), each R2is independently hydrogen, halogen, -CN, -ORa, or -L-cycloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), each R2is independently hydrogen, halogen, or -ORa. In some embodiments of a compound of Formula (IVa) or (IVb), each R2is independently hydrogen or -ORa. In some embodiments of a compound of Formula (IVa) or (IVb), each R2is independently hydrogen, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), each R2is independently hydrogen, halogen, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), each R2is independently hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), each R2is independently hydrogen or halogen. In some embodiments of a compound of Formula (IVa) or (IVb), each R2is hydrogen.

[0162] In some embodiments of a compound of Formula (IVa) or (IVb), RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), RY1is hydrogen, C1-C6alkyl, or C1- C6haloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), RY1is hydrogen or C1- C6alkyl. In some embodiments of a compound of Formula (IVa) or (IVb), RY1is hydrogen. In some embodiments of a compound of Formula (IVa) or (IVb), RY1is C1-C6alkyl independently optionallysubstituted with one or more R. In some embodiments of a compound of Formula (IVa) or (IVb), RY1is C1-C6alkyl. In some embodiments of a compound of Formula (IVa) or (IVb), RY1is ethyl. In some embodiments of a compound of Formula (IVa) or (IVb), one or more hydrogen in RY1is replaced with a deuterium atom. In some embodiments of a compound of Formula (IVa) or (IVb), RY1is -CD2CD3or - CH2CH2OCD3. In some embodiments of a compound of Formula (IVa) or (IVb), RY1is -CD2CD3. In some embodiments of a compound of Formula (IVa) or (IVb), RY1is -CH2CH2OCD3.

[0163] In some embodiments of a compound of Formula (IVa) or (IVb), R4is hydrogen, halogen, -CN, - OH, -ORa, C1-C6alkyl, C1-C6haloalkyl, C1-C6heteroalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R4is hydrogen, halogen, C1-C6alkyl, C1- C6haloalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R4is hydrogen, -CN, -OH, -ORa, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R4is hydrogen, halogen, or C1-C6alkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R4is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R4is hydrogen or halogen. In some embodiments of a compound of Formula (IVa) or (IVb), R4is hydrogen.

[0164] In some embodiments of a compound of Formula (IVb), X3is N. In some embodiments of a compound of Formula (IVb), X3is CR7.

[0165] In some embodiments of a compound of Formula (IVa) or (IVb), R7is hydrogen, halogen, -CN, - OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (IVa) or (IVb), R7is hydrogen, halogen, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (IVa) or (IVb), R7is hydrogen, halogen, C1-C6alkyl, or C2- C6alkynyl. In some embodiments of a compound of Formula (IVa) or (IVb), R7is hydrogen, halogen, or C1-C6alkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R7is hydrogen.

[0166] In some embodiments of a compound of Formula (IV)-(IX), R7is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (IV)-(IX), R7is hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IV)-(IX), R7is C1-C6haloalkyl.

[0167] In some embodiments of a compound of Formula (IVa) or (IVb), R6and R7are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R. In some embodiments of a compound of Formula (IVa) or (IVb), R6and R7are taken together to form a cycloalkyl optionally substituted with one or more R. In some embodiments of a compound of Formula (IVa) or (IVb), R6and R7are taken together to form a heterocycloalkyl optionally substituted with one or more R.

[0168] In some embodiments, the compound of Formula (IVa) or (IVb) has the following formula:wherein the ethyl can be optionally deuterated. In some embodiments, the compound of Formula (IVa) or (IVb) has the following formula:wherein the ethyl can be optionally deuterated.

[0169] In some embodiments, the compound of Formula (IVa) or (IVb) has the following formula:wherein the ethyl can be optionally deuterated. In some embodiments, the compound of Formula (IVa) or (IVb) has the following formula:wherein the ethyl can be optionally deuterated. In some embodiments, the compound of Formula (IVa) or (IVb) has the following formula:wherein the ethyl can be optionally deuterated.

[0170] In some embodiments of a compound of Formula (IVa) or (IVb), R6is hydrogen, halogen, -CN, - OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In someembodiments of a compound of Formula (IVa) or (IVb), R6is hydrogen, halogen, C1-C6alkyl, or C1- C6haloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R6is hydrogen, halogen, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R6is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (IVa) or (IVb), R6is hydrogen, halogen, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (IVa) or (IVb), R6is hydrogen, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (IVa) or (IVb), R6is hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R6is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R6is C1-C6haloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R6is C1- C6alkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R6is halogen or C1- C6haloalkyl. In some embodiments of a compound of Formula (IVa) or (IVb), R6is C1-C6alkyl or C1- C6haloalkyl.

[0171] Disclosed herein is a compound of Formula (V), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R20is -L-NR10C(=O)R11, -L-C(=O)NR12R13, -11 10 11L-S(=O)2R , -L-S(=O)(=NR )R , or - L-P(=O)(R11)2; Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R1is independently halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, - S(=O)2NRcRd, -NRcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L- heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; and / or two R1on the same carbon atom are taken together to form an oxo; n is 0, 1, 2, 3, 4, 5, or 6; R10is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl;R11is C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R12and R13are independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R12and R13are taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; U is C or N; T is C or N; provided that not both of U and T are N; Y1is NRY1, CR3, N, O, or S; R3is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SF5, -SH, - SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, - NRbC(=O)ORb, -NRbS(=O)2Ra, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Y2is NRY2, CR4, N, O, or S; R4is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY2is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein thealkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Y3is N or C; X1is N or CR5; R5is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X2is N or CR6; R6is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R5and R6are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; X3is N or CR7; R7is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R6and R7are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; W is absent, -NH-, -O-, or -S-; Ring C is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R14is independently halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; q is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; and / or two R on the same atom form an oxo.

[0172] In some embodiments of a compound of Formula (V), W is absent. In some embodiments of a compound of Formula (V), W is -NH-.

[0173] In some embodiments of a compound of Formula (V), Ring C is heteroaryl.

[0174] In some embodiments of a compound of Formula (V), Ring C is 5-membered heteroaryl.

[0175] In some embodiments of a compound of Formula (V), Ring C is 5-membered heteroaryl comprising one, two, or three heteroatoms selected from the group consisting of N, O, and S.

[0176] In some embodiments of a compound of Formula (V), Ring C is 5-membered heteroaryl comprising one or two heteroatoms selected from the group consisting of N, O, and S.

[0177] In some embodiments of a compound of Formula (V), Ring C is thiophenyl, furanyl, pyrrolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, triazolyl, oxadiazolyl, or thiadiazolyl.

[0178] In some embodiments of a compound of Formula (V), each R14is independently halogen, C1- C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (V), each R14isindependently halogen or C1-C6alkyl. In some embodiments of a compound of Formula (V), each R14is independently C1-C6alkyl.

[0179] In some embodiments of a compound of Formula (V), q is 0, 1, or 2. In some embodiments of a compound of Formula (V), q is 0 or 1. In some embodiments of a compound of Formula (V), q is 0. In some embodiments of a compound of Formula (V), q is 1.

[0180] In some embodiments of a compound of Formula (V),

[0181] Disclosed herein is a compound of Formula (VI), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R20is, -L-NR10C(=O)R11, -L-C(=O)NR12R13, -L-S(=O)2R11, -L-S(=O)(=NR10)R11, or - L-P(=O)(R11)2; Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R1is independently halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, - S(=O)2NRcRd, -NRcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L- heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; and / or two R1on the same carbon atom are taken together to form an oxo; n is 0, 1, 2, 3, 4, 5, or 6; R10is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl; R11is C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl,heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R12and R13are independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R12and R13are taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; U is C or N; T is C or N; provided that not both of U and T are N; Y1is NRY1, CR3, N, O, or S; R3is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SF5, -SH, - SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, - NRbC(=O)ORb, -NRbS(=O)2Ra, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Y2is NRY2, CR4, N, O, or S; R4is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY2is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Y3is N or C; X1is N or CR5; R5is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; whereinthe alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X2is N or CR6; R6is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R5and R6are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; X3is N or CR7; R7is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R6and R7are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; Ring D is cycloalkyl or heterocycloalkyl; each R15is independently halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, - L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; and / or two R15on the same atom form an oxo; t is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; and / or two R on the same atom form an oxo.

[0182] In some embodiments of a compound of Formula (VI), Ring D is cycloalkyl. In some embodiments of a compound of Formula (VI), Ring D is bicyclic cycloalkyl.

[0183] In some embodiments of a compound of Formula (VI), Ring D is heterocycloalkyl. In some embodiments of a compound of Formula (VI), Ring D is bicyclic heterocycloalkyl.

[0184] In some embodiments of a compound of Formula (VI), each R15is independently halogen, C1- C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (VI), each R15is independently halogen or C1-C6alkyl. In some embodiments of a compound of Formula (VI), each R15is independently C1-C6alkyl.

[0185] In some embodiments of a compound of Formula (VI), t is 0 or 1. In some embodiments of a compound of Formula (VI), t is 0. In some embodiments of a compound of Formula (VI), t is 1.

[0186] In some embodiments of a compound of Formula (VI),

[0187] Disclosed herein is a compound of Formula (VII), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R20is -L-NR10C(=O)R11, -L-C(=O)NR12R13, -L-S(=O)11 10 112R , -L-S(=O)(=NR )R , or - L-P(=O)(R11)2; Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R1is independently halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, - S(=O)2NRcRd, -NRcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L- heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; and / or two R1on the same carbon atom are taken together to form an oxo; n is 0, 1, 2, 3, 4, 5, or 6; R10is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl; R11is C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R12and R13are independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R12and R13are taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; U is C or N;T is C or N; provided that not both of U and T are N; Y1is NRY1, CR3, N, O, or S; R3is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SF5, -SH, - SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, - NRbC(=O)ORb, -NRbS(=O)2Ra, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Y2is NRY2, CR4, N, O, or S; R4is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY2is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Y3is N or C; X1is N or CR5; R5is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X2is N or CR6; R6is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R5and R6are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R;X3is N or CR7; R7is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R6and R7are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; R16and R17are independently hydrogen, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1- C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, or -L-heterocycloalkyl; or R16and R17are taken together to form a cycloalkyl or heterocycloalkyl, each independently optionally substituted with one or more R; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1-C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; and / or two R on the same atom form an oxo.

[0188] In some embodiments of a compound of Formula (VI), R16and R17are independently hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (VI), R16and R17are independently hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (VI), R16and R17are independently hydrogen or C1-C6haloalkyl. In some embodiments of a compound of Formula (VI), R16and R17are independently hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (VI), R16and R17are hydrogen.

[0189] In some embodiments of a compound of Formula (VI), R16and R17are taken together to form a cycloalkyl. In some embodiments of a compound of Formula (VI), R16and R17are taken together to form a heterocycloalkyl.

[0190] Disclosed herein is a compound of Formula (VIII), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R20is -L-NR10C(=O)R11, -L-C(=O)NR12R13, -L-S(=O)2R11, -L-S(=O)(=10 11NR )R , or - L-P(=O)(R11)2; Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R1is independently halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, - S(=O)2NRcRd, -NRcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L- heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; and / or two R1on the same carbon atom are taken together to form an oxo; n is 0, 1, 2, 3, 4, 5, or 6; R10is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl; R11is C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl,heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R12and R13are independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R12and R13are taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; U is C or N; T is C or N; provided that not both of U and T are N; Y1is NRY1, CR3, N, O, or S; R3is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SF5, -SH, - SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, - NRbC(=O)ORb, -NRbS(=O)2Ra, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Y2is NRY2, CR4, N, O, or S; R4is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY2is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;Y3is N or C; X1is N or CR5; R5is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X2is N or CR6; R6is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R5and R6are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; X3is N or CR7; R7is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R6and R7are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; Ring E is bicyclic cycloalkyl, bicyclic heterocycloalkyl, bicyclic aryl, or bicyclic heteroaryl; each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; and / or two R on the same atom form an oxo.

[0191] In some embodiments of a compound of Formula (VIII), Ring E is bicyclic heteroaryl. In some embodiments of a compound of Formula (VIII), Ring E is benzimidazolyl.

[0192] In some embodiments of a compound of Formula (IV)-(X), U is N and T is C. In some embodiments of a compound of Formula (IV)-(X), U is C and T is N. In some embodiments of a compound of Formula (IV)-(X), U is C and T is C.

[0193] In some embodiments of a compound of Formula (IV)-(VIII) or (X), Y1is NRY1. In some embodiments of a compound of Formula (IV)-(VIII) or (X), Y1is CR3.

[0194] In some embodiments of a compound of Formula (IV)-(VIII) or (X), Y2is NRY2. In some embodiments of a compound of Formula (IV)-(VIII) or (X), Y2is CR4. In some embodiments of a compound of Formula (IV)-(VIII) or (X), Y2is N. In some embodiments of a compound of Formula (IV)-(VIII) or (X), Y2is O. In some embodiments of a compound of Formula (IV)-(VIII) or (X), Y2is S.

[0195] In some embodiments of a compound of Formula (IV)-(VIII) or (X), Y3is N. In some embodiments of a compound of Formula (IV)-(VIII) or (X), Y3is C.

[0196] In some embodiments of a compound of Formula (IV)-(IX), X1is N. In some embodiments of a compound of Formula (IV)-(IX), X1is CR5.

[0197] In some embodiments of a compound of Formula (IV)-(IX), X2is N. In some embodiments of a compound of Formula (IV)-(IX), X2is CR6.

[0198] In some embodiments of a compound of Formula (IV)-(IX), X3is N. In some embodiments of a compound of Formula (IV)-(IX), X3is CR7.

[0199] In some embodiments of a compound of Formula (IV)-(VIII),

[0200] In some embodiments of a compound of Formula (IV)-(VIII),

[0201] In some embodiments of a compound of Formula (IV)-(VIII),

[0202] In some embodiments of a compound of Formula (IV)-(VIII),

[0203] In some embodiments of a compound of Formula (IV)-(VIII),

[0204] In some embodiments of a compound of Formula (IV)-(VIII),

[0205] In some embodiments of a compound of Formula (IV)-(VIII),

[0206] In some embodiments of a compound of Formula (IV)-(VIII),

[0207] In some embodiments of a compound of Formula (IV)-(VIII),

[0208] In some embodiments of a compound of Formula (IV)-(VIII),some embodiments of a compound of Formula.

[0209] In some embodiments of a compound of Formula (IV)-(VIII),

[0210] In some embodiments of a compound of Formula (IV)-(VIII),

[0211] In some embodiments of a compound of Formula (IV)-(VIII),

[0212] In some embodiments of a compound of Formula (IV)-(VIII),

[0213] In some embodiments of a compound of Formula (IV)-(VIII),

[0214] In some embodiments of a compound of Formula (IV)-(VIII),

[0215] In some embodiments of a compound of Formula (IV)-(VIII),

[0216] In some embodiments of a compound of Formula (IV)-(VIII),.

[0217] In some embodiments of a compound of Formula (IV)-(VIII),

[0218] In some embodiments of a compound of Formula (IV)-(VIII),

[0219] In some embodiments of a compound of Formula (IV)-(VIII),

[0220] In some embodiments of a compound of Formula (IV)-(VIII),.

[0221] In some embodiments of a compound of Formula (IV)-(IX), R3is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, -L- cycloalkyl, or -L-heterocycloalkyl; wherein the alkyl, heteroalkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (IV)-(IX), R3is hydrogen, -OH, -ORa, C1-C6alkyl, C1-C6haloalkyl, C1-C6heteroalkyl, or -L- cycloalkyl; wherein the alkyl, heteroalkyl, and cycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (IV)-(IX), R3is -ORa, C1-C6alkyl, C1- C6heteroalkyl, or -L-cycloalkyl; wherein the alkyl, heteroalkyl, and cycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (IV)-(IX), R3is C1-C6alkyl. In some embodiments of a compound of Formula (IV)-(IX), R3is hydrogen.

[0222] In some embodiments of a compound of Formula (IV)-(IX), R4is hydrogen, halogen, -CN, -OH, -ORa, C1-C6alkyl, C1-C6haloalkyl, C1-C6heteroalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In someembodiments of a compound of Formula (IV)-(IX), R4is hydrogen, halogen, C1-C6alkyl, C1-C6haloalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (IV)-(IX), R4is hydrogen, -CN, - OH, -ORa, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IV)-(IX), R4is hydrogen, halogen, or C1-C6alkyl. In some embodiments of a compound of Formula (IV)-(IX), R4is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IV)-(IX), R4is hydrogen or halogen. In some embodiments of a compound of Formula (IV)-(IX), R4is hydrogen.

[0223] In some embodiments of a compound of Formula (IV)-(IX), R5is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (IV)-(IX), R5is hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IV)-(IX), R5is hydrogen.

[0224] In some embodiments of a compound of Formula (IV)-(IX), R6is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (IV)-(IX), R6is hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IV)-(IX), R6is hydrogen, halogen, or C1-C6haloalkyl.

[0225] In some embodiments of a compound of Formula (IV)-(IX), R6is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (IV)-(IX), R6is hydrogen, halogen, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (IV)-(IX), R6is hydrogen, -NRcRd, C1-C6alkyl, C1- C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (IV)-(IX), R6is hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IV)-(IX), R6is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IV)-(IX), R6is C1- C6haloalkyl. In some embodiments of a compound of Formula (IV)-(IX), R6is C1-C6alkyl. In some embodiments of a compound of Formula (IV)-(IX), R6is halogen or C1-C6haloalkyl. In some embodiments of a compound of Formula (IV)-(IX), R6is C1-C6alkyl or C1-C6haloalkyl.

[0226] In some embodiments of a compound of Formula (IV)-(IX), R7is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (IV)-(IX), R7is hydrogen, halogen, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (IV)-(IX), R7is hydrogen, halogen, C1-C6alkyl, or C2- C6alkynyl. In some embodiments of a compound of Formula (IV)-(IX), R7is hydrogen, halogen, or C1- C6alkyl. In some embodiments of a compound of Formula (IV)-(IX), R7is hydrogen.

[0227] In some embodiments of a compound of Formula (IV)-(IX), R7is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (IV)-(IX), R7is hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IV)-(IX), R7is C1-C6haloalkyl.

[0228] In some embodiments of a compound of Formula (IV)-(VIII) or (X), RY1is hydrogen, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (IV)-(VIII) or (X), RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (IV)-(VIII) or (X), RY1ishydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IV)-(VIII) or (X), RY1is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IV)-(VIII) or (X), RY1is hydrogen. In some embodiments of a compound of Formula (IV)-(VIII) or (X), RY1is C1-C6alkyl independently optionally substituted with one or more R. In some embodiments of a compound of Formula (IV)-(VIII) or (X), RY1is C1-C6alkyl. In some embodiments of a compound of Formula (IV)- (VIII) or (X), RY1is ethyl. In some embodiments of a compound of Formula (IV)-(VIII) or (X), one or more hydrogen in RY1is replaced with a deuterium atom. In some embodiments of a compound of Formula (IV)-(VIII) or (X), RY1is -CD2CD3or -CH2CH2OCD3. In some embodiments of a compound of Formula (IV)-(VIII) or (X), RY1is -CD2CD3. In some embodiments of a compound of Formula (IV)- (VIII) or (X), RY1is -CH2CH2OCD3.

[0229] In some embodiments of a compound of Formula (IV)-(VIII) or (X), RY2is hydrogen, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (IV)-(VIII) or (X), RY2is hydrogen, C1-C6alkyl, C1-C6haloalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (IV)-(VIII) or (X), RY2is hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IV)-(VIII) or (X), RY2is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IV)-(VIII) or (X), RY2is hydrogen. In some embodiments of a compound of Formula (IV)-(VIII) or (X), RY2is C1-C6alkyl.

[0230] Disclosed herein is a compound of Formula (IX), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R20is -L-NR10C(=O)R11, -L-C(=O)NR12R13, -L-S(=O)2R11, -L-S(=O)(=N10 11R )R , or - L-P(=O)(R11)2; Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R1is independently halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, - S(=O)2NRcRd, -NRcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L- heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;and / or two R1on the same carbon atom are taken together to form an oxo; n is 0, 1, 2, 3, 4, 5, or 6; R10is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl; R11is C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R12and R13are independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R12and R13are taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; U is C or N; T is C or N; provided that not both of U and T are N; X1is N or CR5; R5is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X2is N or CR6; R6is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R5and R6are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; X3is N or CR7; R7is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl,C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R6and R7are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; Ring F is a 5-membered heterocycloalkyl, a 6-membered heterocycloalkyl, or a 6-membered heteroaryl; each R18is independently halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, - L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; and / or two R18on the same atom form an oxo; v is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; andeach R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein the cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more halogen, -CN, -OH, - NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, or C1-C3heteroalkyl; and / or two R on the same atom form an oxo.

[0231] In some embodiments of a compound of Formula (IX), Ring F is a 5-membered heterocycloalkyl. In some embodiments of a compound of Formula (IX), Ring F is a 5-membered heterocycloalkyl comprising one or two heteroatoms that are N.

[0232] In some embodiments of a compound of Formula (IX), Ring F is a 6-membered heterocycloalkyl. In some embodiments of a compound of Formula (IX), Ring F is a 6-membered heterocycloalkyl comprising one or two heteroatoms that are N.

[0233] In some embodiments of a compound of Formula (IX), Ring F is a 6-membered heteroaryl. In some embodiments of a compound of Formula (IX), Ring F is a 6-membered heteroaryl comprising one or two heteroatoms that are N.

[0234] In some embodiments of a compound of Formula (IX), each R18is independently halogen, C1- C6alkyl, or C1-C6haloalkyl; and / or two R18on the same atom form an oxo. In some embodiments of a compound of Formula (IX), each R18is independently C1-C6alkyl or C1-C6haloalkyl; and / or two R18on the same atom form an oxo. In some embodiments of a compound of Formula (IX), each R18is independently C1-C6alkyl; and / or two R18on the same atom form an oxo.

[0235] In some embodiments of a compound of Formula (IX), v is 0, 1, 2, or 3. In some embodiments of a compound of Formula (IX), v is 0, 1, or 2. In some embodiments of a compound of Formula (IX), v is 1 or 2. In some embodiments of a compound of Formula (IX), v is 1. In some embodiments of a compound of Formula (IX), v is 2. In some embodiments of a compound of Formula (IX), v is 3. In some embodiments of a compound of Formula (IX), v is 1, 2, or 3. In some embodiments of a compound of Formula (IX), v is 2 or 3.

[0236] In some embodiments of a compound of Formula (IX),In some embodiments of a compound of Formula (IX),In some embodiments of a compound of Formula (IX),

[0237] In some embodiments, the compound of Formula (IX), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, is of Formula (IXa):wherein: R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R31is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X is -O-, -S-, -NR32-, or -C(R33)2-; R32is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each R33is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Z is independently N or CR2;each R2is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R6is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X3is N or CR7; R7is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein the cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more halogen, -CN, -OH, - NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, or C1-C3heteroalkyl; and / or two R on the same atom form an oxo.

[0238] In some embodiments, the compound of Formula (IX), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, is of Formula (IXb):wherein: R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R31is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X is -O-, -S-, -NR32-, or -C(R33)2-; R32is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein thealkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each R33is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each R3is independently hydrogen, halogen, -CN, C1-C6alkyl, or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R; R6is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X3is N or CR7; R7is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; and / or two R on the same atom form an oxo.

[0239] In some embodiments of a compound of Formula (IXa) or (IXb), R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R30is hydrogen, C1-C6alkyl, or -L-cycloalkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R30is C1-C6alkyl or -L-cycloalkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R30is C1-C6alkyl.

[0240] In some embodiments of a compound of Formula (IXa) or (IXb), R30is -CH3. In some embodiments of a compound of Formula (IXa) or (IXb), R30is -CD3.

[0241] In some embodiments of a compound of Formula (IXa) or (IXb), X is -O-. In some embodiments of a compound of Formula (IXa) or (IXb), X is -S-. In some embodiments of a compound of Formula (IXa) or (IXb), X is -NR32-. In some embodiments of a compound of Formula (IXa) or (IXb), X is - C(R33)2-.

[0242] In some embodiments of a compound of Formula (IXa) or (IXb), R32is hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R32is hydrogen or C1- C6alkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R32is hydrogen. In some embodiments of a compound of Formula (IXa) or (IXb), R32is C1-C6alkyl. In some embodiments of a compound of Formula (IXa) or (IXb), each R33is independently hydrogen, halogen, -OH, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IXa) or (IXb), each R33is independently hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IXa) or (IXb), each R33is hydrogen.

[0243] In some embodiments of a compound of Formula (IXa) or (IXb),

[0244] In some embodiments of a compound of Formula (IXa) or (IXb), each Z is independently CR2. In some embodiments of a compound of Formula (IXa) or (IXb), one Z is N and the remaining Z are independently CR2.

[0245] In some embodiments of a compound of Formula (IXa) or (IXb),

[0246] In some embodiments of a compound of Formula (IXa) or (IXb), each R2is independently hydrogen, halogen, -CN, -OH, -ORa, C1-C6alkyl, or -L-cycloalkyl. In some embodiments of a compound of Formula (IXa) or (IXb), each R2is independently hydrogen, halogen, -CN, -ORa, or -L-cycloalkyl. In some embodiments of a compound of Formula (IXa) or (IXb), each R2is independently hydrogen, halogen, or -ORa. In some embodiments of a compound of Formula (IXa) or (IXb), each R2isindependently hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IXa) or (IXb), each R2is independently hydrogen or halogen. In some embodiments of a compound of Formula (IXa) or (IXb), each R2is hydrogen.

[0247] In some embodiments, the compound of Formula (IXa) has the following formula:.

[0248] In some embodiments of a compound of Formula (IXa), X3is N. In some embodiments of a compound of Formula (IXa), X3is CR7.

[0249] In some embodiments, the compound of Formula (IXa) has the following formula:.

[0250] In some embodiments, the compound of Formula (IXa) has the following formula:.

[0251] In some embodiments, the compound of Formula (IXb) has the following formula:.

[0252] In some embodiments of a compound of Formula (IXb), X3is N. In some embodiments of a compound of Formula (IXb), X3is CR7.

[0253] In some embodiments, the compound of Formula (IXb) has the following formula:.

[0254] In some embodiments, the compound of Formula (IXb) has the following formula:.

[0255] In some embodiments of a compound of Formula (IXa) or (IXb), R31is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, -L-cycloalkyl, or -L- heterocycloalkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R31is hydrogen, -CN, C1-C6alkyl, C1-C6hydroxyalkyl, or -L-cycloalkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R31is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R31is -CN or C1-C6alkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R31is C1- C6alkyl.

[0256] In some embodiments, the compound of Formula (IXa) has the following formula:.

[0257] In some embodiments, the compound of Formula (IXb) has the following formula:.

[0258] In some embodiments of a compound of Formula (IXa), RY1is hydrogen, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (IXa), RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (IXa), RY1is hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IXa), RY1is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IXa), RY1is hydrogen. In some embodiments of a compound of Formula (IXa), RY1is C1-C6alkyl independently optionally substituted with one or more R. In some embodiments of a compound of Formula (IXa), RY1is C1-C6alkyl. In some embodiments of a compound of Formula (IXa), RY1is ethyl. In some embodiments of a compound of Formula (IXa), one or more hydrogen in RY1is replaced with a deuterium atom. In some embodiments of a compound of Formula (IXa), RY1is - CD2CD3or -CH2CH2OCD3. In some embodiments of a compound of Formula (IXa), RY1is -CD2CD3. In some embodiments of a compound of Formula (IXa), RY1is -CH2CH2OCD3.

[0259] In some embodiments of a compound of Formula (IXb), each R3is independently hydrogen, halogen, -CN, C1-C6alkyl, or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (IXb), each R3is independently hydrogen, halogen, -CN, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IXb), each R3is independently hydrogen, halogen, or C1-C6alkyl. In some embodiments of a compound of Formula (IXb), each R3is independently hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IXb), one R3is hydrogen and the other R3is C1-C6alkyl.

[0260] In some embodiments of a compound of Formula (IXa) or (IXb), R7is hydrogen, halogen, -CN, - OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (IXa) or (IXb), R7is hydrogen, halogen, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (IXa) or (IXb), R7is hydrogen, halogen, C1-C6alkyl, or C2- C6alkynyl. In some embodiments of a compound of Formula (IXa) or (IXb), R7is hydrogen, halogen, or C1-C6alkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R7is hydrogen.

[0261] In some embodiments of a compound of Formula (IXa) or (IXb), R7is hydrogen, halogen, C1- C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R7is C1- C6haloalkyl.

[0262] In some embodiments of a compound of Formula (IXa) or (IXb), R6is hydrogen, halogen, -CN, - OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R6is hydrogen, halogen, C1-C6alkyl, or C1- C6haloalkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R6is hydrogen, halogen, or C1-C6haloalkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R6is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (IXa) or (IXb), R6is hydrogen, halogen, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (IXa) or (IXb), R6is hydrogen, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C2-C6alkynyl. In some embodiments of a compound of Formula (IXa) or (IXb), R6is hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula(IXa) or (IXb), R6is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R6is C1-C6haloalkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R6is C1- C6alkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R6is halogen or C1- C6haloalkyl. In some embodiments of a compound of Formula (IXa) or (IXb), R6is C1-C6alkyl or C1- C6haloalkyl.

[0263] Disclosed herein is a compound of Formula (X), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R20is -L-NR10C(=O)R11, -L-C(=O)12 13 11 10 11NR R , -L-S(=O)2R , -L-S(=O)(=NR )R , or - L-P(=O)(R11)2; Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R1is independently halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, - S(=O)2NRcRd, -NRcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L- heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; and / or two R1on the same carbon atom are taken together to form an oxo; n is 0, 1, 2, 3, 4, 5, or 6; R10is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl; R11is C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R12and R13are independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R12and R13are taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R;each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; U is C or N; T is C or N; provided that not both of U and T are N; Y1is NRY1, CR3, N, O, or S; R3is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SF5, -SH, - SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, - NRbC(=O)ORb, -NRbS(=O)2Ra, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Y2is NRY2, CR4, N, O, or S; R4is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY2is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Y3is N or C; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl,heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; Ring G is 6-membered heterocycloalkyl or a 5-membered heteroaryl; each R19is independently halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, - L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; and / or two R19on the same atom form an oxo; and / or two R19are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; w is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein the cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more halogen, -CN, -OH, - NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, or C1-C3heteroalkyl; and / or two R on the same atom form an oxo.

[0264] In some embodiments of a compound of Formula (X), U is N and T is C. In some embodiments of a compound of Formula (X), T is N and U is C. In some embodiments of a compound of Formula (X), U is T and T is C.

[0265] In some embodiments of a compound of Formula (X), Ring G is 6-membered heterocycloalkyl. In some embodiments of a compound of Formula (X), Ring G is 6-membered heterocycloalkyl comprising one or two heteroatoms selected from the group consisting of N, O, and S. In some embodiments of a compound of Formula (X), Ring G is 6-membered heterocycloalkyl comprising one or two heteroatoms selected from the group consisting of N and O. In some embodiments of a compound of Formula (X), Ring G is 6-membered heterocycloalkyl comprising one or two heteroatoms that are N.

[0266] In some embodiments of a compound of Formula (X), Ring G is a 5-membered heteroaryl. In some embodiments of a compound of Formula (X), Ring G is a 5-membered heteroaryl comprising one or two heteroatoms selected from the group consisting of N, O, and S. In some embodiments of a compound of Formula (X), Ring G is a 5-membered heteroaryl comprising one or two heteroatoms selected from the group consisting of N and O. In some embodiments of a compound of Formula (X), Ring G is a 5-membered heteroaryl comprising one or two heteroatoms that are N.

[0267] In some embodiments of a compound of Formula (X), each R19is independently halogen, C1- C6alkyl, or C1-C6haloalkyl; and / or two R19on the same atom form an oxo. In some embodiments of a compound of Formula (X), each R19is independently C1-C6alkyl or C1-C6haloalkyl; and / or two R19on the same atom form an oxo. In some embodiments of a compound of Formula (X), each R19is independently C1-C6alkyl; and / or two R19on the same atom form an oxo.

[0268] In some embodiments of a compound of Formula (X), w is 0, 1, 2, or 3. In some embodiments of a compound of Formula (X), w is 0, 1, or 2. In some embodiments of a compound of Formula (X), w is 1 or 2. In some embodiments of a compound of Formula (X), w is 1. In some embodiments of a compound of Formula (X), w is 2. In some embodiments of a compound of Formula (X), w is 3.

[0269] In some embodiments of a compound of Formula (X),

[0270] In some embodiments of a compound of Formula (X),or.

[0271] Disclosed herein is a compound of Formula (XI), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R20is -L-NR10C(=O)R11, -L-C(=O)NR12R13, -L-S(=O)2R11, -L-S10 11(=O)(=NR )R , or - L-P(=O)(R11)2; R10is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl; R11is C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; U is C or N; T is C or N; provided that not both of U and T are N; Y1is NRY1, CR3, N, O, or S; R3is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, -SF5, -SH, - SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -NRcRd, -NRbC(=O)NRcRd, -NRbC(=O)Ra, - NRbC(=O)ORb, -NRbS(=O)2Ra, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;Y2is NRY2, CR4, N, O, or S; R4is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY2is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X1is N or CR5; R5is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X2is N or CR6; R6is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X3is N or CR7; R7is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X4is N or CR7a; R7ais hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd,C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; and / or two R on the same atom form an oxo.

[0272] In some embodiments of a compound of Formula (XI),is.

[0273] In some embodiments of a compound of Formula (XI),is.

[0274] In some embodiments of a compound of Formula (XI), U is N and T is C. In some embodiments of a compound of Formula (XI), U is C and T is N. In some embodiments of a compound of Formula (XI), U is C and T is C.

[0275] In some embodiments of a compound of Formula (XI), Y1is NRY1. In some embodiments of a compound of Formula (XI), Y1is CR3.

[0276] In some embodiments of a compound of Formula (XI), Y2is NRY2. In some embodiments of a compound of Formula (XI), Y2is CR4. In some embodiments of a compound of Formula (XI), Y2is N. In some embodiments of a compound of Formula (XI), Y2is O. In some embodiments of a compound of Formula (XI), Y2is S.

[0277] In some embodiments of a compound of Formula (XI), X1is N. In some embodiments of a compound of Formula (XI), X1is CR5.

[0278] In some embodiments of a compound of Formula (XI), X2is N. In some embodiments of a compound of Formula (XI), X2is CR6.

[0279] In some embodiments of a compound of Formula (XI), X3is N. In some embodiments of a compound of Formula (XI), X3is CR7.

[0280] In some embodiments of a compound of Formula (XI), X3is N. In some embodiments of a compound of Formula (XI), X4is CR7a.

[0281] In some embodiments of a compound of Formula (XI),

[0282] In some embodiments of a compound of Formula (XI),

[0283] In some embodiments of a compound of Formula (XI),

[0284] In some embodiments of a compound of Formula (XI),.

[0285] In some embodiments of a compound of Formula (XI),

[0286] In some embodiments of a compound of Formula (XI),.

[0287] In some embodiments of a compound of Formula (XI),

[0288] In some embodiments of a compound of Formula (XI),.

[0289] In some embodiments of a compound of Formula (XI), R3is hydrogen, halogen, -CN, -OH, - ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, -L- cycloalkyl, or -L-heterocycloalkyl; wherein the alkyl, heteroalkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (XI), R3is hydrogen, -OH, -ORa, C1-C6alkyl, C1-C6haloalkyl, C1-C6heteroalkyl, or -L- cycloalkyl; wherein the alkyl, heteroalkyl, and cycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (XI), R3is -ORa, C1-C6alkyl, C1- C6heteroalkyl, or -L-cycloalkyl; wherein the alkyl, heteroalkyl, and cycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (XI), R3is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (XI), R3is C1-C6alkyl. In some embodiments of a compound of Formula (XI), R3is hydrogen.

[0290] In some embodiments of a compound of Formula (XI), R4is hydrogen, halogen, -CN, -OH, - ORa, C1-C6alkyl, C1-C6haloalkyl, C1-C6heteroalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (XI), R4is hydrogen, halogen, C1-C6alkyl, C1-C6haloalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (XI), R4is hydrogen, halogen, or C1- C6alkyl. In some embodiments of a compound of Formula (XI), R4is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (XI), R4is hydrogen or halogen. In some embodiments of a compound of Formula (XI), R4is hydrogen.

[0291] In some embodiments of a compound of Formula (XI), R5is hydrogen, halogen, -CN, -OH, - ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (XI), R5is hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XI), R5is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (XI), R5is hydrogen.

[0292] In some embodiments of a compound of Formula (XI), R6is hydrogen, halogen, -CN, -OH, - ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (XI), R6is hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XI), R6is hydrogen, halogen, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XI), R6is halogen or C1-C6haloalkyl. In some embodiments of a compound of Formula (XI), R6is C1-C6alkyl or C1-C6haloalkyl. In some embodiments of a compound of Formula (XI), R6is C1-C6haloalkyl. In some embodiments of a compound of Formula (XI), R6is C1-C6alkyl. In some embodiments of a compound of Formula (XI), R6is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (XI), R6is hydrogen. In some embodiments of a compound of Formula (XI), R6is C1-C6alkyl.

[0293] In some embodiments of a compound of Formula (XI), R7is hydrogen, halogen, -CN, -OH, - ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (XI), R7is hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XI), R7is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (XI), R7is hydrogen. In some embodiments of a compound of Formula (XI), R7is C1-C6haloalkyl. In some embodiments of a compound of Formula (XI), R7is C1-C6alkyl.

[0294] In some embodiments of a compound of Formula (XI), R7ais hydrogen, halogen, -CN, -OH, - ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (XI), R7ais hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XI), R7ais hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (XI), R7ais hydrogen. In some embodiments of a compound of Formula (XI), R7ais C1-C6haloalkyl. In some embodiments of a compound of Formula (XI), R7ais C1-C6alkyl.

[0295] In some embodiments of a compound of Formula (XI), RY1is hydrogen, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (XI), RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (XI), RY1is hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XI), RY1is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (XI), RY1is hydrogen. In some embodiments of a compound of Formula (XI), RY1is C1-C6alkyl.

[0296] In some embodiments of a compound of Formula (XI), RY2is hydrogen, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (XI), RY2is hydrogen, C1-C6alkyl, C1-C6haloalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (XI), RY2is hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XI), RY2is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (XI), RY2is hydrogen. In some embodiments of a compound of Formula (XI), RY2is C1-C6alkyl.

[0297] In some embodiments of a compound of Formula (XI),orIn some embodiments of a compound of Formula (XI),is

[0298] In some embodiments of a compound of Formula (V)-(XI), R20is.

[0299] In some embodiments of a compound of Formula (V)-(XI), Ring A is heterocycloalkyl. In some embodiments of a compound of Formula (V)-(XI), Ring A is 5- or 6-membered heterocycloalkyl. In some embodiments of a compound of Formula (V)-(XI), Ring A is 5-membered heterocycloalkyl. In some embodiments of a compound of Formula (V)-(XI), Ring A is 6-membered heterocycloalkyl.

[0300] In some embodiments of a compound of Formula (V)-(XI), each R1is independently halogen, - CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1- C6heteroalkyl; and / or two R1on the same carbon atom are taken together to form an oxo.

[0301] In some embodiments of a compound of Formula (V)-(XI), each R1is independently C1-C6alkyl; and / or two R1on the same carbon atom are taken together to form an oxo.

[0302] In some embodiments of a compound of Formula (V)-(XI), n is 2, 3, or 4. In some embodiments of a compound of Formula (V)-(XI), n is 3 or 4. In some embodiments of a compound of Formula (V)- (XI), n is 2. In some embodiments of a compound of Formula (V)-(XI), n is 3. In some embodiments of a compound of Formula (V)-(XI), n is 4.

[0303] In some embodiments of a compound of Formula (V)-(XI),wherein: R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R31is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X is -O-, -S-, -NR32-, or -C(R33)2-; R32is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein thealkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each R33is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R.

[0304] In some embodiments of a compound of Formula (V)-(XI), R30is hydrogen, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L- cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl. In some embodiments of a compound of Formula (V)-(XI), R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, -L-cycloalkyl, or -L- heterocycloalkyl. In some embodiments of a compound of Formula (V)-(XI), R30is hydrogen, C1- C6alkyl, or -L-cycloalkyl. In some embodiments of a compound of Formula (V)-(XI), R30is C1-C6alkyl or -L-cycloalkyl. In some embodiments of a compound of Formula (V)-(XI), R30is C1-C6alkyl.

[0305] In some embodiments of a compound of Formula (V)-(XI), R30is -CH3. In some embodiments of a compound of Formula (V)-(XI), R30is -CD3.

[0306] In some embodiments of a compound of Formula (V)-(XI), R31is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl. In some embodiments of a compound of Formula (V)-(XI), R31is hydrogen, halogen, -CN, - OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, -L-cycloalkyl, or -L- heterocycloalkyl.

[0307] In some embodiments of a compound of Formula (V)-(XI), R31is hydrogen, -CN, C1-C6alkyl, C1-C6hydroxyalkyl, or -L-cycloalkyl. In some embodiments of a compound of Formula (V)-(XI), R31is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (V)-(XI), R31is -CN or C1- C6alkyl, In some embodiments of a compound of Formula (V)-(XI), R31is C1-C6alkyl.

[0308] In some embodiments of a compound of Formula (V)-(XI), X is -O-. In some embodiments of a compound of Formula (V)-(XI), X is -S-. In some embodiments of a compound of Formula (V)-(XI), X is -NR32-. In some embodiments of a compound of Formula (V)-(XI), X is -C(R33)2-.

[0309] In some embodiments of a compound of Formula (V)-(XI), R32is hydrogen, C1-C6alkyl, or C1- C6haloalkyl. In some embodiments of a compound of Formula (V)-(XI), R32is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (V)-(XI), R32is hydrogen. In some embodiments of a compound of Formula (V)-(XI), R32is C1-C6alkyl. In some embodiments of a compound of Formula (V)- (XI), each R33is independently hydrogen, halogen, -OH, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (V)-(XI), each R33is independently hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (V)-(XI), each R33is hydrogen.

[0310] In some embodiments of a compound of Formula (V)-(XI),

[0311] In some embodiments of a compound of Formula (V)-(XI),or

[0312] In some embodiments of a compound of Formula (V)-(XI),

[0313] In some embodiments of a compound of Formula (V)-(XI),

[0314] In some embodiments of a compound of Formula (V)-(XI), R20is -NR10C(=O)R11.

[0315] In some embodiments of a compound of Formula (V)-(XI), R20is -L-S(=O)2R11, -L- S(=O)(=NR10)R11, or -L-P(=O)(R11)2.

[0316] In some embodiments of a compound of Formula (V)-(XI), R20is -L-S(=O)2R11.

[0317] In some embodiments of a compound of Formula (V)-(XI), R20is -S(=O)2R11. In some embodiments of a compound of Formula (V)-(XI), R20is -CH2-S(=O)2R11.

[0318] In some embodiments of a compound of Formula (V)-(XI), R20is -L-S(=O)(=NR10)R11. In some embodiments of a compound of Formula (V)-(XI), R20is -S(=O)(=NR10)R11. In some embodiments of a compound of Formula (V)-(XI), R20is -CH2-S(=O)(=NR10)R11.

[0319] In some embodiments of a compound of Formula (V)-(XI), R20is -L-P(=O)(R11)2. In some embodiments of a compound of Formula (V)-(XI), R20is -P(=O)(R11)2. In some embodiments of a compound of Formula (V)-(XI), R20is -CH2-P(=O)(R11)2.

[0320] In some embodiments of a compound of Formula (V)-(XI), R10is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (V)-(XI), R10is C1-C6alkyl. In some embodiments of a compound of Formula (V)-(XI), R10is hydrogen.

[0321] In some embodiments of a compound of Formula (V)-(XI), R11is C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl. In some embodiments of a compound of Formula (V)-(XI), R11is C1-C6alkyl.

[0322] In some embodiments of a compound of Formula (V)-(XI), R20is -C(=O)NR12R13.

[0323] In some embodiments of a compound of Formula (V)-(XI), R12and R13are independently hydrogen or C1-C6alkyl.

[0324] In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI),is

[0325] In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI),isIn some embodiments of a compound of Formula (IV), (V), or (VII)-(XI),In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI), In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI), In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI),

[0326] In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI),isIn some embodiments of a compound of Formula (IV), (V), or (VII)-(XI),

[0327] In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI), each R2is independently hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, -L-cycloalkyl, or -L-heterocycloalkyl.

[0328] In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI), each R2is independently hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl.

[0329] In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI), each R2is independently hydrogen, halogen, -CN, -OH, -ORa, C1-C6alkyl, or -L-cycloalkyl.

[0330] In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI), each R2is independently hydrogen, halogen, -CN, -ORa, or -L-cycloalkyl.

[0331] In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI), each R2is independently hydrogen, halogen, or -ORa.

[0332] In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI), each R2is independently hydrogen or -ORa.

[0333] In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI), each R2is independently hydrogen, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl.

[0334] In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI), each R2is independently hydrogen, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, or C1-C6heteroalkyl.

[0335] In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI), each R2is independently hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl.

[0336] In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI), each R2is independently hydrogen or halogen.

[0337] In some embodiments of a compound of Formula (IV), (V), or (VII)-(XI), each R2is hydrogen.

[0338] Disclosed herein is a compound of Formula (XII), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein the alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R; R31is hydrogen, halogen, -CN, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, -L-cycloalkyl, or -L- heterocycloalkyl; wherein the alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R; each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, C1-C6alkyl, or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R; is a single or a double bond; U is N or C; T is N or C; provided that U and T are not both N; Y1is N, NRY1, CR3, or C(R3)2; each R3is independently hydrogen, halogen, -CN, C1-C6alkyl, or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R; RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6heteroalkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein the alkyl, heteroalkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R; Y2is N, NRY2, CR4, C(R4)2, or C(=O); each R4is independently hydrogen, halogen, -CN, C1-C6alkyl, or C1-C6haloalkyl; wherein the alkyl is independently optionally substituted with one or more R; RY2is hydrogen, C1-C6alkyl, or C1-C6haloalkyl; wherein the alkyl is independently optionally substituted with one or more R;Y3is N or C; X1is N or CR5; R5is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, C1-C6alkyl, or C1-C6haloalkyl; wherein the alkyl is independently optionally substituted with one or more R; X2is N or CR6; R6is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, C1-C6alkyl, or C1-C6haloalkyl; wherein the alkyl is independently optionally substituted with one or more R; X3is N or CR7; R7is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, C1-C6alkyl, or C1-C6haloalkyl; wherein the alkyl is independently optionally substituted with one or more R; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R8is independently halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1- C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein the cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more halogen, -CN, -OH, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, or C1-C3heteroalkyl; and / or two R on the same atom form an oxo.

[0339] Disclosed herein is a compound of Formula (XIII), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein the alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R; R31is hydrogen, halogen, -CN, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, -L-cycloalkyl, or -L- heterocycloalkyl; wherein the alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R; each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, C1-C6alkyl, or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R; is a single or a double bond; U is N or C; T is N or C; provided that U and T are not both N; Y1is N, NRY1, CR3, or C(R3)2; each R3is independently hydrogen, halogen, -CN, C1-C6alkyl, or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R; RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6heteroalkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein the alkyl, heteroalkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R; Y2is N, NRY2, CR4, C(R4)2, or C(=O); each R4is independently hydrogen, halogen, -CN, C1-C6alkyl, or C1-C6haloalkyl; wherein the alkyl is independently optionally substituted with one or more R; RY2is hydrogen, C1-C6alkyl, or C1-C6haloalkyl; wherein the alkyl is independently optionally substituted with one or more R; Y3is N or C; X1is N or CR5;R5is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, C1-C6alkyl, or C1-C6haloalkyl; wherein the alkyl is independently optionally substituted with one or more R; X2is N or CR6; R6is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, C1-C6alkyl, or C1-C6haloalkyl; wherein the alkyl is independently optionally substituted with one or more R; X3is N or CR7; R7is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, C1-C6alkyl, or C1-C6haloalkyl; wherein the alkyl is independently optionally substituted with one or more R; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R8is independently halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1- C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein the cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more halogen, -CN, -OH, - NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, or C1-C3heteroalkyl; and / or two R on the same atom form an oxo.

[0340] In some embodiments of a compound of Formula (XII) or (XIII), R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), R30is hydrogen, C1-C6alkyl or -L-cycloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), R30is hydrogen, C1-C6alkyl, or cycloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), R30is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (XII) or (XIII), R30is C1-C6alkyl.

[0341] In some embodiments of a compound of Formula (XII) or (XIII), R30is -CH3. In some embodiments of a compound of Formula (XII) or (XIII), R30is -CD3.

[0342] In some embodiments of a compound of Formula (XII) or (XIII),iswhich is fully aromatic. In some embodiments of a compound of Formula (XII) or (XIII),is not aromatic.

[0343] In some embodiments of a compound of Formula (XII) or (XIII), U is N and T is C. In some embodiments of a compound of Formula (XII) or (XIII), U is C and T is N. In some embodiments of a compound of Formula (XII) or (XIII), U is C and T is C.

[0344] In some embodiments of a compound of Formula (XII) or (XIII), Y1is NRY1, CR3, or C(R3)2. In some embodiments of a compound of Formula (XII) or (XIII), Y1is NRY1. In some embodiments of a compound of Formula (XII) or (XIII), Y1is CR3. In some embodiments of a compound of Formula (XII) or (XIII), Y1is C(R3)2.

[0345] In some embodiments of a compound of Formula (XII) or (XIII), Y2is CR4or C(=O). In some embodiments of a compound of Formula (XII) or (XIII), Y2is CR4. In some embodiments of a compound of Formula (XII) or (XIII), Y2is C(=O).

[0346] In some embodiments of a compound of Formula (XII) or (XIII), Y3is N. In some embodiments of a compound of Formula (XII) or (XIII), Y3is C.

[0347] In some embodiments of a compound of Formula (XII) or (XIII), U is C, T is C, Y1is NRY1or CR3, Y2is CR4or C(=O), and Y3is N or C.

[0348] In some embodiments of a compound of Formula (XII) or (XIII), U is C, T is C, Y1is NRY1, Y2is CR4, and Y3is C.

[0349] In some embodiments of a compound of Formula (XII) or (XIII), U is C, T is C, Y1is NRY1, Y2is C(=O), and Y3is N.

[0350] In some embodiments of a compound of Formula (XII) or (XIII), U is C, T is N, Y1is CR3, Y2is CR4, and Y3is C.

[0351] In some embodiments of a compound of Formula (XII) or (XIII), X1is CR5, X2is CR6, and X3is CR7.

[0352] In some embodiments of a compound of Formula (XII) or (XIII), X1is N, X2is CR6, and X3is CR7.

[0353] In some embodiments of a compound of Formula (XII) or (XIII), X1is CR5, X2is N, and X3is CR7.

[0354] In some embodiments of a compound of Formula (XII) or (XIII), X1is CR5, X2is CR6, and X3is N.

[0355] In some embodiments of a compound of Formula (XII) or (XIII), X1is N, X2is CR6, and X3is N.

[0356] In some embodiments of a compound of Formula (XII) or (XIII), is

[0357] In some embodiments of a compound of Formula (XII) or (XIII),is

[0358] In some embodiments of a compound of Formula (XII) or (XIII), is

[0359] In some embodiments of a compound of Formula (XII) or (XIII), is

[0360] In some embodiments of a compound of Formula (XII) or (XIII), is

[0361] In some embodiments of a compound of Formula (XII) or (XIII), is

[0362] In some embodiments of a compound of Formula (XII) or (XIII),is

[0363] In some embodiments of a compound of Formula (XII) or (XIII), is

[0364] In some embodiments of a compound of Formula (XII) or (XIII), is

[0365] In some embodiments of a compound of Formula (XII) or (XIII), is

[0366] In some embodiments of a compound of Formula (XII) or (XIII), is

[0367] In some embodiments of a compound of Formula (XII) or (XIII), is

[0368] In some embodiments of a compound of Formula (XII) or (XIII),

[0369] In some embodiments of a compound of Formula (XII) or (XIII),

[0370] In some embodiments of a compound of Formula (XII) or (XIII), each Z is independently CR2. In some embodiments of a compound of Formula (XII) or (XIII), one Z is N and the remaining Z are independently CR2.

[0371] In some embodiments of a compound of Formula (XII) or (XIII),

[0372] In some embodiments of a compound of Formula (XII) or (XIII), each R2is independently hydrogen, halogen, -CN, or C1-C6alkyl. In some embodiments of a compound of Formula (XII) or (XIII), each R2is independently hydrogen, halogen, or C1-C6alkyl. In some embodiments of a compound of Formula (XII) or (XIII), each R2is independently hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (XII) or (XIII), each R2is independently hydrogen or halogen. In some embodiments of a compound of Formula (XII) or (XIII), each R2is independently hydrogen.

[0373] In some embodiments of a compound of Formula (XII) or (XIII),In

[0374] In some embodiments, the compound of Formula (XII) has the following formula:.

[0375] In some embodiments, the compound of Formula (XII) has the following formula:.

[0376] In some embodiments, the compound of Formula (XII) has the following formula:.

[0377] In some embodiments, the compound of Formula (XIII) has the following formula:.

[0378] In some embodiments, the compound of Formula (XIII) has the following formula:.

[0379] In some embodiments, the compound of Formula (XIII) has the following formula:.

[0380] In some embodiments of a compound of Formula (XII) or (XIII), R31is hydrogen, halogen, -CN, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein the alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (XII) or (XIII), R31is hydrogen, halogen, -CN, C1-C6alkyl, C1- C6haloalkyl, C1-C6hydroxyalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), R31is hydrogen, -CN, C1-C6alkyl, C1-C6haloalkyl, C1- C6hydroxyalkyl, or -L-cycloalkyl. C6haloalkyl, C1-C6hydroxyalkyl, -L-cycloalkyl, or -L- heterocycloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), R31is -CN, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, or -L-cycloalkyl. In some embodiments of a compound ofFormula (XII) or (XIII), R31is -CN or C1-C6alkyl. In some embodiments of a compound of Formula (XII) or (XIII), R31is -CN.

[0381] In some embodiments of a compound of Formula (XII) or (XIII), each R3is independently hydrogen, halogen, -CN, C1-C6alkyl, or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (XII) or (XIII), each R3is independently hydrogen, halogen, -CN, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), each R3is independently hydrogen, halogen, or C1-C6alkyl. In some embodiments of a compound of Formula (XII) or (XIII), each R3is independently hydrogen or C1- C6alkyl. In some embodiments of a compound of Formula (XII) or (XIII), each R3is hydrogen.

[0382] In some embodiments of a compound of Formula (XII) or (XIII), RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6heteroalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), RY1is C1-C6alkyl, C1-C6heteroalkyl, or -L-cycloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), RY1is C1-C6alkyl, C1-C6heteroalkyl, or cycloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), RY1is C1-C6alkyl or C1- C6heteroalkyl. In some embodiments of a compound of Formula (XII) or (XIII), RY1is C1-C6alkyl. In some embodiments of a compound of Formula (XII) or (XIII), RY1is C1-C6alkyl or C1-C6heteroalkyl, wherein the alkyl is optionally substituted with one or more deuterium. In some embodiments of a compound of Formula (XII) or (XIII), RY1is C1-C6alkyl optionally substituted with one or more deuterium. In some embodiments of a compound of Formula (XII) or (XIII), RY1is -CH2CH3. In some embodiments of a compound of Formula (XII) or (XIII), RY1is -CD2CD3. In some embodiments of a compound of Formula (XII) or (XIII), RY1is -CH2CH2OCD3.

[0383] In some embodiments of a compound of Formula (XII) or (XIII), R4is hydrogen, halogen, -CN, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), R4is hydrogen, halogen, -CN, or C1-C6alkyl. In some embodiments of a compound of Formula (XII) or (XIII), R4is hydrogen, halogen, or C1-C6alkyl. In some embodiments of a compound of Formula (XII) or (XIII), R4is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (XII) or (XIII), R4is hydrogen.

[0384] In some embodiments of a compound of Formula (XII) or (XIII), RY2is hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), RY2is hydrogen or C1- C6alkyl. In some embodiments of a compound of Formula (XII) or (XIII), RY2is C1-C6alkyl.

[0385] In some embodiments of a compound of Formula (XII) or (XIII), R5is hydrogen, halogen, -CN, - OH, -ORa, -NRcRd, -C(=O)Ra, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), R5is hydrogen, halogen, -CN, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), R5is hydrogen, halogen, -CN, or C1-C6alkyl. In some embodiments of a compound of Formula (XII) or (XIII), R5is hydrogen, halogen, or C1-C6alkyl. In some embodiments of a compound of Formula (XII) or (XIII), R5is hydrogen or halogen. In some embodiments of a compound of Formula (XII) or (XIII), R5is hydrogen or C1-C6alkyl. In some embodiments of a compound of Formula (XII) or (XIII), R5is hydrogen.

[0386] In some embodiments of a compound of Formula (XII) or (XIII), R6is hydrogen, halogen, -CN, - OH, -ORa, -NRcRd, -C(=O)Ra, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), R6is hydrogen, halogen, -CN, -ORa, -C(=O)Ra, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), R6is hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), R6is C1-C6alkyl or C1- C6haloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), R6is C1-C6alkyl.

[0387] In some embodiments of a compound of Formula (XII) or (XIII), R7is hydrogen, halogen, -CN, - OH, -ORa, -NRcRd, -C(=O)Ra, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), R7is hydrogen, halogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), R7is hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (XII) or (XIII), R7is hydrogen or C1-C6haloalkyl.

[0388] In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), Ring B is aryl or heteroaryl. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), Ring B is phenyl or 5- or 6- membered heteroaryl.

[0389] In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), Ring B is phenyl.

[0390] In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), Ring B is 6-membered heteroaryl. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), Ring B is pyridinyl, pyrimidinyl, or pyrazinyl. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), Ring B is pyridinyl.

[0391] In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), Ring B is 5-membered heteroaryl.

[0392] In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), each R8is independently halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, - C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), each R8is independently halogen, -CN, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, or -L-heteroaryl; wherein each alkyl and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), each R8is independently halogen, -CN, -C(=O)NRcRd, C1-C6alkyl, or -L-heteroaryl. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), each R8is independently halogen, -C(=O)NRcRd, C1-C6alkyl, or -L-heteroaryl.

[0393] In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), each R8is independently -L-heteroaryl; wherein each heteroaryl isindependently optionally substituted with one or more R. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), each R8is independently halogen or heteroaryl; wherein each heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), each R8is independently heteroaryl; wherein each heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), each R8is independently a 5-membered heteroaryl comprising one, two, or three heteroatoms selected from the group consisting of O, N, and S; wherein each heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)- (XIII), each R8is independently a 5-membered heteroaryl comprising one or two heteroatoms selected from the group consisting of O, N, and S; wherein each heteroaryl is independently optionally substituted with one or more R.

[0394] In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), each R8is independently halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, - C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)- (XIII), each R8is independently halogen, -CN, -OH, -ORa, -C(=O)NRcRd, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), each R8is independently halogen, -CN, -ORa, -C(=O)NRcRd, or C1-C6alkyl. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)- (XIII), each R8is independently halogen, -CN, -C(=O)NRcRd, or C1-C6alkyl. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), each R8is independently -CN, -C(=O)NRcRd, or C1-C6alkyl. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), each R8is independently -C(=O)NRcRd. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), each R8is independently halogen or -C(=O)NRcRd. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), each R8is independently halogen or -C(=O)NH(heteroaryl) wherein the heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), each R8is independently -C(=O)NH(heteroaryl) wherein the heteroaryl is independently optionally substituted with one or more R.

[0395] In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), m is 1, 2, or 3. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), m is 2 or 3. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), m is 1 or 2. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)- (XIII), m is 0. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII),(IX), (IXa), (IXb), (X)-(XIII), m is 1. In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII), m is 2.

[0396] In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII),

[0397] In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII),In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII),, , , In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII),,

[0398] In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII),wherein: Ring H is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R8ais hydrogen, halogen, -CN, C1-C6alkyl, or C1-C6haloalkyl; each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; and u is 0, 1, 2, 3, or 4.

[0399] In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII),wherein: Ring H is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R8ais hydrogen, halogen, -CN, C1-C6alkyl, or C1-C6haloalkyl; each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; and u is 0, 1, 2, 3, or 4.

[0400] In some embodiments, Ring H is a heteroaryl. In some embodiments, Ring H is a 5-membered heteroaryl. In some embodiments, Ring H is a 5-membered heteroaryl comprising one or twoheteroatoms selected from the group consisting of N, O, and S. In some embodiments, Ring H is a 5- membered heteroaryl comprising one or two heteroatoms selected from the group consisting of N and O. In some embodiments, Ring H is a 5-membered heteroaryl comprising one or two heteroatoms that are N.

[0401] In some embodiments, u is 0, 1, or 2. In some embodiments, u is 1 or 2. In some embodiments, u is 0. In some embodiments, u is 1. In some embodiments, u is 2.

[0402] In some embodiments, R8ais hydrogen, halogen, or C1-C6alkyl. In some embodiments, R8ais hydrogen or halogen. In some embodiments, R8ais hydrogen, halogen, or C1-C6alkyl. In some embodiments, R8ais hydrogen. In some embodiments, R8ais hydrogen, halogen, or C1-C6alkyl. In some embodiments, R8ais halogen.

[0403] In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII),

[0404] In some embodiments of a compound of Formula (I), (II), (IV), (IVa), (IVb), (V)-(VII), (IX), (IXa), (IXb), (X)-(XIII),

[0405] In some embodiments of a compound disclosed herein, one or more hydrogen has been replaced by a deuterium.

[0406] In some embodiments of a compound disclosed herein, three hydrogens have been replaced by a deuterium.

[0407] In some embodiments of a compound disclosed herein, five hydrogens have been replaced by a deuterium.

[0408] In some embodiments of a compound disclosed herein, one or more hydrogen in R30has been replaced by a deuterium. In some embodiments of a compound disclosed herein, three hydrogens in R30have been replaced by a deuterium.

[0409] In some embodiments of a compound disclosed herein, one or more hydrogen in R31has been replaced by a deuterium. In some embodiments of a compound disclosed herein, three hydrogens in R31have been replaced by a deuterium.

[0410] In some embodiments of a compound disclosed herein, one or more hydrogen in RY1has been replaced by a deuterium. In some embodiments of a compound disclosed herein, three hydrogens in RY1have been replaced by a deuterium. In some embodiments of a compound disclosed herein, five hydrogens in RY1have been replaced by a deuterium.

[0411] In some embodiments of a compound disclosed herein, one or more hydrogen in R3has been replaced by a deuterium. In some embodiments of a compound disclosed herein, three hydrogens in R3have been replaced by a deuterium.

[0412] In some embodiments of a compound disclosed herein, one or more hydrogen in R8has been replaced by a deuterium. In some embodiments of a compound disclosed herein, three hydrogens in R8have been replaced by a deuterium.

[0413] In some embodiments of a compound disclosed herein, each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, -L-cycloalkyl, or -L- heterocycloalkyl; wherein each alkyl, heteroalkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each Rais independently C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl; wherein each alkyl and heteroalkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each Rais independently C1-C6alkyl or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each Rais independently C1-C6alkyl or C1-C6haloalkyl. In some embodiments of a compound disclosed herein, each Rais independently C1-C6alkyl. In some embodiments of a compound disclosed herein, each Rais independently C1-C6haloalkyl.

[0414] In some embodiments of a compound disclosed herein, each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, -L-cycloalkyl, or - L-heterocycloalkyl; wherein each alkyl, heteroalkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl; wherein eachalkyl and heteroalkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each Rbis independently hydrogen, C1-C6alkyl or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each Rbis independently hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound disclosed herein, each Rbis independently hydrogen or C1-C6alkyl. In some embodiments of a compound disclosed herein, each Rbis independently hydrogen or C1-C6haloalkyl. In some embodiments of a compound disclosed herein, each Rbis hydrogen. In some embodiments of a compound disclosed herein, each Rbis independently C1-C6alkyl. In some embodiments of a compound disclosed herein, each Rbis independently C1-C6haloalkyl.

[0415] In some embodiments of a compound disclosed herein, each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, -L- cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl, heteroalkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, -L-cycloalkyl, or -L- heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl; wherein each alkyl and heteroalkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each Rcand Rdare independently hydrogen, C1-C6alkyl or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each Rcand Rdare independently hydrogen, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments of a compound disclosed herein, each Rcand Rdare independently hydrogen or C1-C6alkyl. In some embodiments of a compound disclosed herein, each Rcand Rdare independently hydrogen or C1-C6haloalkyl. In some embodiments of a compound disclosed herein, each Rcand Rdare hydrogen. In some embodiments of a compound disclosed herein, each Rcand Rdare independently C1-C6alkyl. In some embodiments of a compound disclosed herein, each Rcand Rdare independently C1-C6haloalkyl.

[0416] In some embodiments of a compound disclosed herein, each Rcand Rdare independently hydrogen, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each Rcand Rdare independently hydrogen, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, each Rcand Rdare independently hydrogen or heteroaryl independently optionally substituted with one or more R.

[0417] In some embodiments of a compound disclosed herein, Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R.

[0418] In some embodiments of a compound disclosed herein, L is absent. In some embodiments of a compound disclosed herein, L is C1-C3alkylene independently optionally substituted with one or more R. In some embodiments of a compound disclosed herein, L is C1-C3alkylene. In some embodiments of a compound disclosed herein, L is -CH2-. In some embodiments of a compound disclosed herein, L is - CH2CH2-. In some embodiments of a compound disclosed herein, L is -CH2CH2CH2-.

[0419] In some embodiments of a compound disclosed herein, each R is independently halogen, -CN, - OH, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1-C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, - C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1- C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6- membered heterocycloalkyl; and / or two R on the same atom form an oxo. In some embodiments of a compound disclosed herein, each R is independently halogen, -CN, -OH, -NH2, -NHC1-C3alkyl, -N(C1- C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1- C3aminoalkyl, or C1-C3heteroalkyl; and / or two R on the same atom form an oxo. In some embodiments of a compound disclosed herein, each R is independently halogen, -CN, -OH, -NH2, C1-C3alkyl, C1- C3alkoxy, or C1-C3haloalkyl; and / or two R on the same atom form an oxo. In some embodiments of a compound disclosed herein, each R is independently halogen, -CN, C1-C3alkyl, or C1-C3haloalkyl; and / or two R on the same atom form an oxo.

[0420] Any combination of the groups described above for the various variables is contemplated herein. Throughout the specification, groups and substituents thereof are chosen by one skilled in the field to provide stable moieties and compounds.

[0421] In some embodiments the compound disclosed herein, is selected from a compound found in table 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof. Table 1

[0422] In some embodiments the compound disclosed herein, is selected from a compound that is:or a pharmaceutically acceptable salt, solvate, or stereoisomerthereof.

[0423] In some embodiments the compound disclosed herein, is selected from a compound that is:or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[0424] In some embodiments the compound disclosed herein, is selected from a compound that is:or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[0425] In some embodiments the compound disclosed herein, is selected from a compound that is:or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[0426] In some embodiments the compound disclosed herein, is selected from a compound that is:or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[0427] In some embodiments the compound disclosed herein, is selected from a compound that is:,or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[0428] In some embodiments the compound disclosed herein, is selected from a compound that is:or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[0429] In some embodiments the compound disclosed herein, is selected from a compound that is:or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[0430] In some embodiments the compound disclosed herein, is selected from a compound that is:or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[0431] In some embodiments the compound disclosed herein, is selected from a compound that is:or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.Further Forms of Compounds Disclosed HereinIsomers / Stereoisomers

[0432] In some embodiments, the compounds described herein exist as geometric isomers. In some embodiments, the compounds described herein possess one or more double bonds. The compoundspresented herein include all cis, trans, syn, anti, entgegen (E), and zusammen (Z) isomers as well as the corresponding mixtures thereof. In some situations, the compounds described herein possess one or more chiral centers and each center independently exists in the R configuration or S configuration. The compounds described herein include all diastereomeric, enantiomeric, and epimeric forms as well as the corresponding mixtures thereof. In additional embodiments of the compounds and methods provided herein, mixtures of enantiomers and / or diastereoisomers, resulting from a single preparative step, combination, or interconversion are useful for the applications described herein. In some embodiments, the compounds described herein are prepared as their individual stereoisomers by reacting a racemic mixture of the compound with an optically active resolving agent to form a pair of diastereoisomeric compounds, separating the diastereomers and recovering the optically pure enantiomers. In some embodiments, dissociable complexes are preferred. In some embodiments, the diastereomers have distinct physical properties (e.g., melting points, boiling points, solubilities, reactivity, etc.) and are separated by taking advantage of these dissimilarities. In some embodiments, the diastereomers are separated by chiral chromatography, or preferably, by separation / resolution techniques based upon differences in solubility. In some embodiments, the optically pure enantiomer is then recovered, along with the resolving agent, by any practical means that would not result in racemization. Labeled compounds

[0433] In some embodiments, the compounds described herein exist in their isotopically-labeled forms. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such isotopically-labeled compounds. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such isotopically-labeled compounds as pharmaceutical compositions. Thus, in some embodiments, the compounds disclosed herein include isotopically-labeled compounds, which are identical to those recited herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into compounds disclosed herein include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, and chlorine, such as2H,3H,13C,14C,l5N,18O,17O,31P,32P,35S,18F, and36Cl, respectively. Compounds described herein, and the pharmaceutically acceptable salts, solvates, or stereoisomers thereof which contain the aforementioned isotopes and / or other isotopes of other atoms are within the scope of this invention. Certain isotopically-labeled compounds, for example those into which radioactive isotopes, such as3H and14C, are incorporated, are useful in drug and / or substrate tissue distribution assays. Tritiated, i.e.,3H and carbon-14, i.e.,14C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavy isotopes, such as deuterium, i.e.,2H, produces certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements. In some embodiments, one or more hydrogen in a compound disclosed herein has been replaced by a deuterium atom. In some embodiments, one or more alkyl substituents in a compound disclosed herein has been replaced by a deuteroalkyl substituents. In some embodiments, one or more -CH3in a compound disclosed herein has been replaced by a -CD3.

[0434] In some embodiments, the compounds described herein are labeled by other means, including, but not limited to, the use of chromophores or fluorescent moieties, bioluminescent labels, or chemiluminescent labels.Pharmaceutically acceptable salts

[0435] In some embodiments, the compounds described herein exist as their pharmaceutically acceptable salts. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such pharmaceutically acceptable salts. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such pharmaceutically acceptable salts as pharmaceutical compositions.

[0436] In some embodiments, the compounds described herein possess acidic or basic groups and therefore react with any of a number of inorganic or organic bases, and inorganic and organic acids, to form a pharmaceutically acceptable salt. In some embodiments, these salts are prepared in situ during the final isolation and purification of the compounds disclosed herein, or a solvate, or stereoisomer thereof, or by separately reacting a purified compound in its free form with a suitable acid or base, and isolating the salt thus formed.

[0437] Examples of pharmaceutically acceptable salts include those salts prepared by reaction of the compounds described herein with a mineral, organic acid or inorganic base, such salts including, but not limited to, acetate, acrylate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, bisulfite, bromide, butyrate, butyn-l,4-dioate, camphorate, camphorsulfonate, caproate, caprylate, chlorobenzoate, chloride, citrate, cyclopentanepropionate, decanoate, digluconate, gluconate, dihydrogenphosphate, dinitrobenzoate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptanoate, glycerophosphate, glycolate, hemisulfate, heptanoate, hexanoate, hexyne- 1,6-dioate, hydroxybenzoate, y-hydroxybutyrate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, iodide, isobutyrate, lactate, maleate, malonate, methanesulfonate, mandelate metaphosphate, methoxybenzoate, methylbenzoate, monohydrogenphosphate, 1-napthalene sulfonate, 2-napthalenesulfonate, nicotinate, nitrate, palmoate, pectinate, persulfate, 3 -phenylpropionate, phosphate, picrate, pivalate, propionate, pyrosulfate, pyrophosphate, propiolate, phthalate, phenylacetate, phenylbutyrate, propanesulfonate, salicylate, succinate, sulfate, sulfite, succinate, suberate, sebacate, sulfonate, tartrate, thiocyanate, tosylate, undecanoate, and xylene sulfonate.

[0438] Further, the compounds described herein can be prepared as pharmaceutically acceptable salts formed by reacting the free base form of the compound with a pharmaceutically acceptable inorganic or organic acid, including, but not limited to, inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid metaphosphoric acid, and the like; and organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, p-toluenesulfonic acid, tartaric acid, trifluoroacetic acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, arylsulfonic acid, methane sulfonic acid, ethane sulfonic acid, 1,2 -ethanedisulfonic acid, 2- hydroxyethanesulfonic acid, benzenesulfonic acid, 2-naphthalenesulfonic acid, 4-methylbicyclo-[2.2.2]oct-2-ene-1-carboxylic acid, glucoheptonic acid, 4,4’-methylenebis-(3-hydroxy-2-ene-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid and muconic acid. In some embodiments, other acids, such as oxalic, while not in themselves pharmaceutically acceptable, are employed in the preparation of salts useful as intermediates in obtaining the compounds disclosed herein, solvate, or stereoisomer thereof and their pharmaceutically acceptable acid addition salts.

[0439] In some embodiments, those compounds described herein which comprise a free acid group react with a suitable base, such as the hydroxide, carbonate, bicarbonate, sulfate, of a pharmaceutically acceptable metal cation, with ammonia, or with a pharmaceutically acceptable organic primary, secondary, tertiary, or quaternary amine. Representative salts include the alkali or alkaline earth salts, like lithium, sodium, potassium, calcium, and magnesium, and aluminum salts and the like. Illustrative examples of bases include sodium hydroxide, potassium hydroxide, choline hydroxide, sodium carbonate, N+(C1-C4alkyl)4hydroxide, and the like.

[0440] Representative organic amines useful for the formation of base addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine and the like. It should be understood that the compounds described herein also include the quaternization of any basic nitrogen- containing groups they contain. In some embodiments, water or oil-soluble or dispersible products are obtained by such quaternization. Solvates

[0441] In some embodiments, the compounds described herein exist as solvates. The invention provides for methods of treating diseases by administering such solvates. The invention further provides for methods of treating diseases by administering such solvates as pharmaceutical compositions.

[0442] Solvates contain either stoichiometric or non-stoichiometric amounts of a solvent, and, in some embodiments, are formed with pharmaceutically acceptable solvents, such as water, ethanol, and the like. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. Solvates of the compounds described herein can be conveniently prepared or formed during the processes described herein. By way of example only, hydrates of the compounds described herein can be conveniently prepared from an aqueous / organic solvent mixture, using organic solvents including, but not limited to, dioxane, tetrahydrofuran or methanol. In addition, the compounds provided herein can exist in unsolvated as well as solvated forms. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the compounds and methods provided herein. Method of Treatment

[0443] Disclosed herein are methods of modulating STAT6 activity in a subject, comprising administering to the subject a compound described herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[0444] In some embodiments, the disorder responsive to the modulation (e.g., inhibition) of STAT6 include, but is not limited to, allergic disorder, atherosclerosis, autoimmune diseases such as lupus andrheumatoid arthritis, autoinflammatory syndromes, cancer, cardiovascular disorder, CNS disorder, condition associated with cell death, conditions associated with organ transplantation, destructive bone disorder, diabetes, gout and gouty arthritis, hereditary disorder, hormone -related disease, immunodeficiency disorder, infectious disease, inflammatory bowel disease, inflammatory disorder, liver disease, metabolic disorder, neurodegenerative disorder, neurological disorder, osteoarthritis, pathologic immune conditions involving T cell activation, proliferative disorder, psoriasis, thrombin-induced platelet aggregation, viral disease, and Waldenstrom’s Macroglobulinemia.

[0445] Proliferative disorders, include, but are not limited to a benign or malignant tumor, solid tumor, liquid tumor, carcinoma of the brain, kidney, liver, adrenal gland, bladder, breast, stomach, gastric tumors, ovaries, colon, rectum, prostate, pancreas, lung, vagina, cervix, testis, genitourinary tract, esophagus, larynx, skin, bone or thyroid, sarcoma, glioblastomas, neuroblastomas, multiple myeloma, gastrointestinal cancer, especially colon carcinoma or colorectal adenoma, a tumor of the neck and head, an epidermal hyperproliferation, psoriasis, prostate hyperplasia, a neoplasia, a neoplasia of epithelial character, adenoma, adenocarcinoma, keratoacanthoma, epidermoid carcinoma, large cell carcinoma, non-small-cell lung carcinoma, lymphomas (Hodgkin and non-Hodgkin), a mammary carcinoma, follicular carcinoma, undifferentiated carcinoma, papillary carcinoma, seminoma, melanoma, an IL -I driven disorder, an MyD88 driven disorder, smoldering of indolent multiple myeloma, or hematological malignancies (including leukemia, diffuse large B-cell lymphoma (DLBCL), ABC DLBCL, chronic lymphocytic leukemia (CLL), chronic lymphocytic lymphoma, primary effusion lymphoma, Burkitt lymphoma / leukemia, acute lymphocytic leukemia, B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenstrom’s macroglobulinemia (WM), splenic marginal zone lymphoma, multiple myeloma, plasmacytoma, intravascular large B-cell lymphoma).

[0446] In some embodiments, the cancer is selected from glioma, breast cancer, prostate cancer, head and neck squamous cell carcinoma, skin melanomas, ovarian cancer, malignant peripheral nerve sheath tumors (MPNST), and pancreatic cancer. In other embodiments, the cancer to be treated is cancer selected from glioma, breast cancer, prostate cancer, head and neck squamous cell carcinoma, skin melanomas, ovarian cancer, malignant peripheral nerve sheath tumors (MPNST), pancreatic cancer, nonsmall cell lung cancer (NSCLC) including EGFR-mutant NSCLC, urothelial cancer, liver cancer, bile duct cancer, kidney cancer, colon cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumors, and hematological malignancies include lymphomas, leukemias, myelomas, myeloproliferative neoplasms and myelodysplastic syndromes.

[0447] In some embodiments, the cancer is solid tumors (e.g., prostate cancer, renal cancer, hepatic cancer, pancreatic cancer, gastric cancer, breast cancer, lung cancer, cancers of the head and neck, thyroid cancer, glioblastoma, Kaposi's sarcoma, Castleman's disease, uterine leiomyosarcoma, melanoma etc.), hematological cancers (e.g., lymphoma, leukemia Such as acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML) or multiple myeloma), and skin cancer such as cutaneous T-cell lymphoma (CTCL), or cutaneous B-cell lymphoma.

[0448] treatment of inflammatory or obstructive airways diseases, resulting, for example, in reduction of tissue damage, airways inflammation, bronchial hyperreactivity, remodeling or disease progression. Inflammatory or obstructive airways diseases include asthma of whatever type or genesis including both intrinsic (non-allergic) asthma and extrinsic (allergic) asthma, mild asthma, moderate asthma, severe asthma, asthmatic bronchitis, exercise-induced asthma, occupational asthma and asthma induced following bacterial infection. Treatment of asthma is also to be understood as embracing treatment of subjects, e.g. of less than 4 or 5 years of age, exhibiting wheezing symptoms and diagnosed or diagnosable as "wheezy infants", an established patient category of major medical concern and now often identified as incipient or early-phase asthmatics.

[0449] In some embodiments, the disorder responsive to the modulation (e.g., inhibition) of STAT6 is heteroimmune diseases including, but are not limited to, graft versus host disease, transplantation, transfusion, anaphylaxis, allergies (e.g., allergies to plant pollens, latex, drugs, foods, insect poisons, animal hair, animal dander, dust mites, or cockroach calyx), type I hypersensitivity, allergic conjunctivitis, allergic rhinitis, and atopic dermatitis.

[0450] In some embodiments, the disorder responsive to the modulation (e.g., inhibition) of STAT6 is other inflammatory or obstructive airways diseases and conditions to which the present invention is applicable and include acute lung injury (ALI), adult / acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary, airways or lung disease (COPD, COAD or COLD), including chronic bronchitis or dyspnea associated therewith, emphysema, as well as exacerbation of airways hyperreactivity consequent to other drug therapy, in particular other inhaled drug therapy. Compounds, salts, and compositions described herein are also useful in the treatment of bronchitis including, but not limited to, acute, arachidic, catarrhal, croupous, chronic or phthinoid bronchitis. Compounds, salts, and compositions described herein are also useful in the treatment of pneumoconiosis (an inflammatory, commonly occupational, disease of the lungs, frequently accompanied by airways obstruction, whether chronic or acute, and occasioned by repeated inhalation of dusts) of whatever type or genesis, including, for example, aluminosis, anthracosis, asbestosis, chalicosis, ptilosis, siderosis, silicosis, tabacosis and byssinosis.

[0451] In some embodiments, the disorder responsive to the modulation (e.g., inhibition) of STAT6 is inflammatory or allergic conditions of the skin, for example psoriasis, contact dermatitis, atopic dermatitis, alopecia areata, erythema multiforma, dermatitis herpetiformis, scleroderma, vitiligo, hypersensitivity angiitis, urticaria, bullous pemphigoid, lupus erythematosus, systemic lupus erythematosus, pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus, epidermolysis bullosa acquisita (EBA), acne vulgaris, and other inflammatory or allergic conditions of the skin.

[0452] In some embodiments, the disorder responsive to the modulation (e.g., inhibition) of STAT6 is a disorder having an inflammatory component, for example, treatment of diseases and conditions of the eye such as ocular allergy, conjunctivitis, keratoconjunctivitis sicca, and vernal conjunctivitis, diseases affecting the nose including allergic rhinitis, and inflammatory disease in which autoimmune reactions are implicated or having an autoimmune component or etiology, including autoimmune hematologicaldisorders (e.g. hemolytic anemia, aplastic anemia, pure red cell anemia and idiopathic thrombocytopenia), systemic lupus erythematosus, rheumatoid arthritis, polychondritis, scleroderma, Wegener granulomatosis, dermatomyositis, chronic active hepatitis, myasthenia gravis, Steven-Johnson syndrome, idiopathic sprue, autoimmune inflammatory bowel disease (e.g. ulcerative colitis and Crohn's disease), irritable bowel syndrome, celiac disease, periodontitis, hyaline membrane disease, kidney disease, glomerular disease, alcoholic liver disease, multiple sclerosis, endocrine ophthalmopathy, Grave's disease, sarcoidosis, alveolitis, chronic hypersensitivity pneumonitis, multiple sclerosis, primary biliary cirrhosis, uveitis (anterior and posterior), Sjogren’s syndrome, keratoconjunctivitis sicca and vernal keratoconjunctivitis, interstitial lung fibrosis, psoriatic arthritis, systemic juvenile idiopathic arthritis, cryopyrin-associated periodic syndrome, nephritis, vasculitis, diverticulitis, interstitial cystitis, glomerulonephritis (with and without nephrotic syndrome, e.g. including idiopathic nephrotic syndrome or minal change nephropathy), chronic granulomatous disease, endometriosis, leptospirosis renal disease, glaucoma, retinal disease, ageing, headache, pain, complex regional pain syndrome, cardiac hypertrophy, muscle wasting, catabolic disorders, obesity, fetal growth retardation, hypercholesterolemia, heart disease, chronic heart failure, mesothelioma, anhidrotic ectodermal dysplasia, Behcet’s disease, incontinentia pigmenti, Paget’s disease, pancreatitis, hereditary periodic fever syndrome, asthma (allergic and non-allergic, mild, moderate, severe, bronchitis, and exercise-induced), acute lung injury, acute respiratory distress syndrome, eosinophilia, hypersensitivities, anaphylaxis, nasal sinusitis, ocular allergy, silica induced diseases, COPD (reduction of damage, airways inflammation, bronchial hyperreactivity, remodeling or disease progression), pulmonary disease, cystic fibrosis, acid induced lung injury, pulmonary hypertension, polyneuropathy, cataracts, muscle inflammation in conjunction with systemic sclerosis, inclusion body myositis, myasthenia gravis, thyroiditis, Addison’s disease, lichen planus, Type 1 diabetes, or Type 2 diabetes, appendicitis, atopic dermatitis, asthma, allergy, blepharitis, bronchiolitis, bronchitis, bursitis, cervicitis, cholangitis, cholecystitis, chronic graft rejection, colitis, conjunctivitis, Crohn’s disease, cystitis, dacryoadenitis, dermatitis, dermatomyositis, encephalitis, encephalomyelitis, endocarditis, endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibrositis, gastritis, gastroenteritis, Henoch-Schonlein purpura, hepatitis, hidradenitis suppurativa, immunoglobulin A nephropathy, interstitial lung disease, laryngitis, mastitis, meningitis, myelitis myocarditis, myositis, nephritis, oophoritis, orchitis, osteitis, otitis, pancreatitis, parotitis, pericarditis, peritonitis, pharyngitis, pleuritis, phlebitis, pneumonitis, pneumonia, polymyositis, proctitis, prostatitis, pyelonephritis, rhinitis, salpingitis, sinusitis, stomatitis, synovitis, tendonitis, tonsillitis, ulcerative colitis, uveitis, vaginitis, vasculitis, or vulvitis.

[0453] In some embodiments, the disorder responsive to the modulation (e.g., inhibition) of STAT6 is cardiovascular diseases including, but are not limited to, restenosis, cardiomegaly, atherosclerosis, myocardial infarction, ischemic stroke, congestive heart failure, angina pectoris, reocclusion after angioplasty, restenosis after angioplasty, reocclusion after aortocoronary bypass, restenosis after aortocoronary bypass, stroke, transitory ischemia, a peripheral arterial occlusive disorder, pulmonary embolism, and deep venous thrombosis.

[0454] In some embodiments, the disorder responsive to the modulation (e.g., inhibition) of STAT6 is a neurodegenerative disease including, but are not limited to, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, cerebral ischemia, and neurodegenerative disease caused by traumatic injury, glutamate neurotoxicity, hypoxia, epilepsy, treatment of diabetes, metabolic syndrome, obesity, organ transplantation and graft versus host disease.

[0455] In some embodiments, the disorder responsive to the modulation (e.g., inhibition) of STAT6 is alopecia, aspergillus, asthma, atomic dermatitis, chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis with nasal polyposis, gastritis, inflammatory bowel disease, pemphigoid, prurigo nodularis, sinusitis, or urticaria.Dosing

[0456] In certain embodiments, the compositions containing the compound(s) described herein are administered for therapeutic treatments. In certain therapeutic applications, the compositions are administered to a patient already suffering from a disease or condition, in an amount sufficient to cure or at least partially arrest at least one of the symptoms of the disease or condition. Amounts effective for this use depend on the severity and course of the disease or condition, previous therapy, the patient’s health status, weight, and response to the drugs, and the judgment of the treating physician. Therapeutically effective amounts are optionally determined by methods including, but not limited to, a dose-escalation.Routes of Administration

[0457] Suitable routes of administration include, but are not limited to, oral, intravenous, rectal, aerosol, parenteral, ophthalmic, pulmonary, transmucosal, transdermal, vaginal, otic, nasal, and topical administration. In addition, by way of example only, parenteral delivery includes intramuscular, subcutaneous, intravenous, intramedullary injections, as well as intrathecal, direct intraventricular, intraperitoneal, intralymphatic, and intranasal injections.

[0458] In certain embodiments, a compound as described herein is administered in a local rather than systemic manner, for example, via injection of the compound directly into an organ, often in a depot preparation or sustained release formulation. In specific embodiments, long-acting formulations are administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Furthermore, in other embodiments, the drug is delivered in a targeted drug delivery system, for example, in a liposome coated with organ specific antibody. In such embodiments, the liposomes are targeted to and taken up selectively by the organ. In yet other embodiments, the compound as described herein is provided in the form of a rapid release formulation, in the form of an extended-release formulation, or in the form of an intermediate release formulation.Pharmaceutical Compositions / Formulations

[0459] The compounds described herein are administered to a subject in need thereof, either alone or in combination with pharmaceutically acceptable carriers, excipients, or diluents, in a pharmaceuticalcomposition, according to standard pharmaceutical practice. In some embodiments, the compounds described herein are administered to animals.

[0460] In another aspect, provided herein are pharmaceutical compositions comprising a compound described herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, and at least one pharmaceutically acceptable excipient. Pharmaceutical compositions are formulated in a conventional manner using one or more pharmaceutically acceptable excipients that facilitate processing of the active compounds into preparations that can be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen. A summary of pharmaceutical compositions described herein can be found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington’s Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, H.A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y., 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams & Wilkins 1999), herein incorporated by reference for such disclosure.Combination

[0461] Disclosed herein are methods of treating a disease or disorder associated with STAT6 using a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, in combination with an additional therapeutic agent.

[0462] In some embodiments, the additional therapeutic agent is administered at the same time as the compound disclosed herein. In some embodiments, the additional therapeutic agent and the compound disclosed herein are administered sequentially. In some embodiments, the additional therapeutic agent is administered less frequently than the compound disclosed herein. In some embodiments, the additional therapeutic agent is administered more frequently than the compound disclosed herein. In some embodiments, the additional therapeutic agent is administered prior than the administration of the compound disclosed herein. In some embodiments, the additional therapeutic agent is administered after the administration of the compound disclosed herein.EXAMPLES

[0463] The following examples are offered to illustrate, but not to limit the claimed invention. The following examples further illustrate the invention but, of course, should not be construed as in any way limiting its scope.

[0464] The following synthetic schemes are provided for purposes of illustration, not limitation. The following examples illustrate the various methods of making compounds described herein. It is understood that one skilled in the art may be able to make these compounds by similar methods or by combining other methods known to one skilled in the art. It is also understood that one skilled in the art would be able to make, in a similar manner as described below by using the appropriate starting materials and modifying the synthetic route as needed. In general, starting materials and reagents can be obtainedfrom commercial vendors or synthesized according to sources known to those skilled in the art or prepared as described herein.

[0465] In some embodiments, the compounds described herein are prepared from substituted 2- aminearyl (1) and arylbromoketone (2) to afford intermediate 3 as shown in Scheme 1. Bromination of intermediate 3 followed by Suzuki coupling with vinyl boronic acid provided intermediate 5 after hydrogenation reaction. Intermediate 6 coupled with different amines (7) yielded the final targets 8.SCHEME 1

[0466] In some embodiments, the compounds described herein are prepared as shown in Scheme 2. Intermediate 9 can be prepared using the procedures described in WO 2009 / 112832. Intermediate 9 reacted with hydrazine intermediate 10 under basic conditions and cyclizes to pyrazole intermediates 11 under palladium mediated reaction. Alcohol deprotection followed by oxidation reaction provided intermediate 12 which reacted with Br2in acetic acid to yield intermediate 13. Suzuki reaction of intermediate 13 with vinyl boronic acid followed by hydrogenation led to intermediate 14. Ester hydrolysis reaction of 14 and amide coupling reaction of resulted acid with different amines provide final targets 15.SCHEME 2Synthesis of Example 1

[0467] To a solution of 4-iodoaniline (37 g, 169 mmol) in 1 -butanol (370 mL) was added hydrazinecarboxylic acid (2.9 g, 16.9 mmol), methyl ester (18.5 g, 205 mmol), and triethyl orthoacetate (33 g, 203 mmol) under nitrogen atmosphere. The resulting solution was stirred at 118 °C overnight under nitrogen atmosphere. The solution mixture was concentrated under vacuum. Water (500 mL) andethyl acetate (500 mL) were added and the aqueous phase was extracted with ethyl acetate (2×500 mL). The combined organic extracts were washed with water (2×1 L) and brine (2×1 L), dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product was purified by column chromatography (petroleum ether / ethyl acetate = 1:1) to afford 4-(4-iodophenyl)-5-methyl-2H-1,2,4- triazol-3-one (19 g, 37.4% yield) as a brown solid. LCMS (ESI, m / z): 302 [M+H]+.

[0468] To a solution of 4-(4-iodophenyl)-5-methyl-2H-1,2,4-triazol-3-one (38 g, 126 mmol) in DMF (100 mL), was added NaH (60% w / w, 4.54 g, 189 mmol) in portions at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 0.5 h under nitrogen atmosphere. To the above mixture was added methyl iodide (21.5 g, 152 mmol) dropwise at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 2 h under nitrogen atmosphere. The reaction was quenched by adding water (500 mL), extracted with ethyl acetate (2x500 mL). The combined organic extracts were washed with brine (1 L), dried over anhydrous sodium sulfate and concentrated under vacuum to afford 4-(4-iodophenyl)-2,5-dimethyl-1,2,4-triazol-3-one (32 g, 80.5% yield) as a black solid. LCMS (ESI, m / z): 316 [M+H]+.

[0469] To a solution of 4-bromo-6-(trifluoromethyl)-2H-indazole (8 g, 30.2 mmol) and Et3N (15.3 g, 151 mmol) in methanol (200 mL), was added Pd(dppf)Cl2.CH2Cl2(7.40 g, 9.06 mmol) and Dppf (10.0 g, 18.1 mmol) under nitrogen atmosphere. The mixture was recharged with carbon monoxide gas three times and the resulting mixture was stirred under carbon monoxide atmospheres (50 atm) at 110 °C for overnight. The mixture was concentrated under vacuum. The crude product was purified by column chromatography (petroleum ether / ethyl acetate = 1:1) to afford methyl 6-(trifluoromethyl)-2H-indazole- 4-carboxylate (6 g, 81.4% yield) as a yellow oil. LCMS (ESI, m / z): 245 [M+H]+.

[0470] To a solution of methyl 6-(trifluoromethyl)-2H-indazole-4-carboxylate (350 mg, 1.43 mmol) in DCM (15 mL), were added 4-(1,3-dimethyl-5-oxo-1,2,4-triazol-4-yl)phenyl 2,4,6-trimethylphenyl trifluoromethanesulfonoperoxoyl iodide (1.25 g, 2.15 mmol) and CuCl (114 mg, 1.15 mmol) under nitrogen atmosphere. The resulting solution was stirred at 50 °C for 2 days under nitrogen atmosphere. The reaction was concentrated under vacuum. The crude product was purified by column chromatography (DCM / MeOH = 10:1) to afford methyl 2-[4-(1,3-dimethyl-5-oxo-1,2,4-triazol-4- yl)phenyl]-6-(trifluoromethyl)indazole-4-carboxylate (310 mg, 50.1% yield) as a brown solid. LCMS (ESI, m / z): 432 [M+H]+.

[0471] To a solution of methyl 2-[4-(1,3-dimethyl-5-oxo-1,2,4-triazol-4-yl)phenyl]-6- (trifluoromethyl)indazole-4-carboxylate (420 mg, 0.97 mmol) in MeCN (20 mL), was added NBS (1.04 g, 5.84 mmol) under nitrogen atmosphere. The resulting solution was stirred at 80 °C for 2 days under nitrogen atmosphere. The reaction was concentrated under vacuum. The reaction was then quenched by adding water (50 mL) and extracted with ethyl acetate (2x50 mL). The combined organic extracts were washed with water (100 mL) and brine (100 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product was purified by column chromatography (ethyl acetate) to afford methyl 3-bromo-2-[4-(1,3-dimethyl-5-oxo-1,2,4-triazol-4-yl)phenyl]-6-(trifluoromethyl)indazole- 4-carboxylate (420 mg, 84.5% yield) as a yellow solid. LCMS (ESI, m / z): 510 / 512 [M+H]+.

[0472] To a solution of methyl 3-bromo-2-[4-(1,3-dimethyl-5-oxo-1,2,4-triazol-4-yl)phenyl]-6- (trifluoromethyl)indazole-4-carboxylate (100 mg, 0.20 mmol) in 1,4-dioxane (4 mL), were added Tributyl(vinyl) tin (93.2 mg, 0.294 mmol) and Pd(PPh3)4 (45.3 mg, 0.039 mmol) under nitrogen atmosphere. The resulting solution was stirred at 80°C overnight under nitrogen atmosphere. The reaction was concentrated under vacuum. The crude product was purified by column chromatography (ethyl acetate) to afford methyl 2-[4-(1,3-dimethyl-5-oxo-1,2,4-triazol-4-yl)phenyl]-3-ethenyl-6- (trifluoromethyl)indazole-4-carboxylate (80 mg, 89.2% yield) as a yellow oil. LCMS (ESI, m / z): 458 [M+H]+.

[0473] To a solution of methyl 2-[4-(1,3-dimethyl-5-oxo-1,2,4-triazol-4-yl)phenyl]-3-ethenyl-6- (trifluoromethyl)indazole-4-carboxylate (140 mg, 0.31 mmol) in methanol (6 mL) was added Pd(OH)2(140 mg), the reaction mixture was recharged with nitrogen gas three times and then recharged with hydrogen gas three times. The mixture was stirred at room temperature for overnight under hydrogen atmosphere. Solids were filtered out and the solvent was evaporated under vacuum to afford methyl 2-[4- (1,3-dimethyl-5-oxo-1,2,4-triazol-4-yl)phenyl]-3-ethyl-6-(trifluoromethyl)indazole-4-carboxylate (80 mg, 56.9% yield) as a yellow oil. LCMS (ESI, m / z): 460 [M+H]+.

[0474] To a solution of methyl 2-[4-(1,3-dimethyl-5-oxo-1,2,4-triazol-4-yl)phenyl]-3-ethyl-6- (trifluoromethyl)indazole-4-carboxylate (80 mg, 0.17 mmol) in methanol (2 mL) and H2O (1 mL), were added LiOH (20.9 mg, 0.87 mmol) under nitrogen atmosphere. The resulting solution was stirred at 50 °C for overnight under nitrogen atmosphere. The reaction was concentrated under vacuum. The crude product was purified by flash column chromatography to afford 2-[4-(1,3-dimethyl-5-oxo-1,2,4-triazol-4- yl)phenyl]-3-ethyl-6-(trifluoromethyl)indazole-4-carboxylic acid (35 mg, 45.1% yield) as a yellow oil. LCMS (ESI, m / z): 446 [M+H]+.

[0475] To a solution of 2-[4-(1,3-dimethyl-5-oxo-1,2,4-triazol-4-yl)phenyl]-3-ethyl-6- (trifluoromethyl)indazole-4-carboxylic acid (30 mg, 0.05 mmol) in DMF (2 mL), was added DIEA (32.7 mg, 0.26 mmol) and HATU (28.8 mg, 0.08 mmol) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 10 min under nitrogen atmosphere. To the above mixture was added 3-aminobenzamide (10.32 mg, 0.08 mmol) at room temperature for overnight under nitrogen atmosphere. The reaction was purified by Prep-HPLC. The pure fractions were combined and concentrated under vacuum to remove organic solvents. The residual aqueous solution was lyophilized overnight to afford N-(3-carbamoylphenyl)-2-[4-(1,3-dimethyl-5-oxo- 1,2,4-triazol-4-yl)phenyl]-3-ethyl-6-(trifluoromethyl)indazole-4-carboxamide (10.3 mg, 36.2% yield, 97.6%purity). LCMS (ESI, m / z): 355 / 357 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 10.89 (s, 1H), 8.31 (s, 1H), 8.25 (s, 1H), 7.99 - 7.97 (m, 2 H), 7.84 - 7.82 (m, 2H), 7.75 - 7.72 (m, 2H), 7.66 - 7.63 (m, 1H), 7.59 (s, 1H), 7.49 - 7.47 (m, 1H), 7.40 (s, 1H), 3.39 (s, 3H), 3.10 - 3.06 (m, 2H), 2.33 (s, 3H), 1.11 - 1.01 (m, 3H).Synthesis of Example 2

[0476] To a solution of 4-bromoaniline (70 g, 406 mmol) in 1-butanol (700 mL) was added hydrazinecarboxylic acid, methyl ester (44 g, 488 mmol), and triethyl orthoacetate (79 g, 488 mmol) under nitrogen atmosphere. The resulting solution was stirred at 118 °C for overnight under nitrogen atmosphere. The solution mixture was concentrated under vacuum. The reaction was then quenched by adding water (500 mL) and extracted with ethyl acetate (3×500 mL). The combined organic extracts were washed with water (1000 mL) and brine (1000 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product was purified by column chromatography (petroleum ether / ethyl acetate = 1:1) to afford 4-(4-bromophenyl)-5-methyl-2H-1,2,4-triazol-3-one (30 g, 29% yield) as a light-yellow solid. LCMS (ESI, m / z): 254, 256 [M+H]+.

[0477] To a solution of 4-(4-bromophenyl)-5-methyl-2H-1,2,4-triazol-3-one (38 g, 142 mmol) in DMF (700 mL), was added NaH (60% w / w, 5.11 g, 213 mmol) in portions at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 0.5 h under nitrogen atmosphere. To the above mixture was added methyl iodide (24.2 g, 170 mmol) drop wise at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 2 h under nitrogen atmosphere. The reaction was quenched by adding NH4Cl (aq.) (50 mL) and water (2 L) at 0 °C, extracted with ethyl acetate (2×2 L). The combined organic extracts were washed with water (2×5 L) and brine (2×5 L), driedover anhydrous sodium sulfate and concentrated under vacuum to afford 4-(4-bromophenyl)-2,5- dimethyl-1,2,4-triazol-3-one (30 g, 78.75% yield) as a light-yellow solid. LCMS (ESI, m / z): 268, 270 [M+H]+.

[0478] To a solution of 4-(4-bromophenyl)-2,5-dimethyl-2,4-dihydro-3H-1,2,4-triazol-3-one (5 g, 18.7 mmol) and (Bpin)2(7.1 g, 28.1 mmol) in 1,4-dioxane (150 mL), was added KOAc (5.5 g, 56.1 mmol) and Pd(dppf)Cl2·CH2Cl2(3.1 g, 3.74 mmol) under nitrogen atmosphere. The resulting mixture was stirred at 80 °C for 2 h under nitrogen atmosphere. The resulting solution was concentrated under vacuum. The crude product was purified by flash column chromatography to afford (4-(1,3-dimethyl-5-oxo-1,5- dihydro-4H-1,2,4-triazol-4-yl)phenyl)boronic acid (4 g, 90% yield) as a light yellow solid. LCMS (ESI, m / z): 233 [M+H]+.

[0479] A solution of KOH (13 g, 231 mmol, 2.5 equiv) in N,N-dimethylacetamide (400 mL) was stirred at 60 °C for 0.5 h under nitrogen atmosphere. To the above solution were added 2,3-dichloro-5- (trifluoromethyl)pyridine (20 g, 92.6 mmol) and dimethyl malonate (12.2 g, 92.6 mmol) at 60 °C under nitrogen atmosphere. The resulting mixture was stirred at 60 °C for 2 h under nitrogen atmosphere. Solids were filtered out and the solvent was quenched by adding water (1.2 L), extracted with ethyl acetate (2×1.2 L). The combined organic extracts were washed with water (2×2.4 L) and brine (2×2.4 L), dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product was purified by column chromatography (petroleum ether / ethyl acetate = 5:1) to afford 1,3-dimethyl 2-[3-chloro-5- (trifluoromethyl)pyridin-2-yl]propanedioate (24 g, 83.1% yield) as a yellow oil. LCMS (ESI, m / z): 312, 314 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 9.01 - 8.95 (m, 1H), 8.63 - 8.58 (m, 1H), 5.54 (s, 1H), 3.75 (s, 6H).

[0480] To a solution of 1,3-dimethyl 2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]propanedioate (5 g, 16.1 mmol) in DMSO (100 mL), was added 30% NaCl (aq.) (60 mL). The resulting solution was stirred at 110 °C for 2 days under nitrogen atmosphere. The reaction was then quenched by adding water (300 mL) and extracted with ethyl acetate (2×300 mL). The combined organic extracts were washed with water (2×600 mL) and brine (2×600 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product was purified by column chromatography (petroleum ether / ethyl acetate = 4:1) to afford methyl 2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]acetate (1.5 g, 36.8% yield) as a yellow oil. LCMS (ESI, m / z): 254, 256 [M+H]+.

[0481] To a solution of methyl 2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]acetate (5 g, 19.7 mmol) in DCM (150 mL), was added amino 2,4,6-trimethylbenzenesulfonate (12.7 g, 59.2 mmol) at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 2 days under nitrogen atmosphere. The solution mixture was concentrated under vacuum and purified by flash column chromatography to afford 4-chloro-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-2-ol (1.5 g, 32.2% yield) as a yellow solid. LCMS (ESI, m / z): 237, 239 [M+H]+.

[0482] To a solution of 4-chloro-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-2-ol (600 mg, 2.54 mmol) and DIEA (984 mg, 7.61 mmol) in DCM (20 mL), was added triflic anhydride (1.08 g, 3.81 mmol) at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 2 h undernitrogen atmosphere. The reaction was quenched by adding water (100 mL), extracted with DCM (2×100 mL). The combined organic extracts were washed with water (200 mL) and brine (200 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product was purified by TLC (petroleum ether / ethyl acetate = 10:1) to afford 4-chloro-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-2-yl trifluoromethanesulfonate (700 mg, 74.9% yield) as a yellow solid. LCMS (ESI, m / z): 369, 371 [M+H]+.

[0483] To a solution of 4-chloro-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-2-yl trifluoromethanesulfonate (700 mg, 1.90 mmol) and 2,5-dimethyl-4-[4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)phenyl]-1,2,4-triazol-3-one (600 mg, 1.90 mmol) in 1,4-dioxane (12 mL) and H2O (3 mL), were added K2CO3(788 mg, 5.70 mmol) and Pd(dppf)Cl2.CH2Cl2(312 mg, 0.38 mmol) under nitrogen atmosphere. The resulting mixture was stirred at 80 °C for 2 h under nitrogen atmosphere. Solids were filtered out and the solvent was evaporated under vacuum. The crude product was purified by flash column chromatography to afford 4-{4-[4-chloro-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-2- yl]phenyl}-2,5-dimethyl-1,2,4-triazol-3-one (350 mg, 45.2% yield) as a yellow solid. LCMS (ESI, m / z): 408, 410 [M+H]+.

[0484] To a solution of 4-{4-[4-chloro-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,5- dimethyl-1,2,4-triazol-3-one (350 mg, 0.86 mmol) in methanol (10 mL), was added Et3N (261 mg, 2.58 mmol), Dppf (286 mg, 0.52 mmol) and Pd(dppf)Cl2.CH2Cl2(211 mg, 0.26 mmol) in a pressure tank. The mixture was purged with nitrogen and then was pressurized to 5 MPa with carbon monoxide at 110°C for 2 days. Solids were filtered out and the solvent was evaporated under vacuum. The crude product was purified by flash column chromatography to afford methyl 2-[4-(1,3-dimethyl-5-oxo-1,2,4-triazol-4- yl)phenyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine-4-carboxylate (17 mg, 4.6% yield) as a yellow solid. LCMS (ESI, m / z): 432 [M+H]+.

[0485] To a solution of methyl 2-[4-(1,3-dimethyl-5-oxo-1,2,4-triazol-4-yl)phenyl]-6- (trifluoromethyl)pyrazolo[1,5-a]pyridine-4-carboxylate (17 mg, 0.039 mmol) in methanol (1 mL) and H2O (0.5 mL), was added LiOH (4.72 mg, 0.195 mmol) at room temperature. The resulting mixture was stirred at 50 °C for 3 h. The mixture product was adjusted to PH 2 with HCl (1M). The resulting solution was stirred for 0.5 h at room temperature. The mixture was extracted with ethyl acetate (2×20 mL). The combined organic extracts were washed with water (40 mL) and brine (40 mL), dried over anhydrous sodium sulfate and concentrated under vacuum to afford the crude product 2-[4-(1,3-dimethyl-5-oxo- 1,2,4-triazol-4-yl)phenyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine-4-carboxylic acid (15 mg, 90.1% yield) as a yellow solid. LCMS (ESI, m / z): 418 [M+H]+.

[0486] To a solution of 2-[4-(1,3-dimethyl-5-oxo-1,2,4-tr...

Claims

CLAIMS WHAT IS CLAIMED IS:

1. A compound of Formula (IVb), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R31is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X is -O-, -S-, -NR32-, or -C(R33)2-; R32is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each R33is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R4is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R6is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X3is N or CR7; R7is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or R6and R7are taken together to form a cycloalkyl or heterocycloalkyl; each independently optionally substituted with one or more R; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein the cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more halogen, -CN, -OH, - NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, or C1-C3heteroalkyl; and / or two R on the same atom form an oxo.

2. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: R4is hydrogen or C1-C6alkyl.

3. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: R4is C1-C6alkyl.

4. A compound of Formula (IXa), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;R31is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X is -O-, -S-, -NR32-, or -C(R33)2-; R32is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each R33is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; RY1is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R6is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X3is N or CR7; R7is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein the cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more halogen, -CN, -OH, - NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, or C1-C3heteroalkyl; and / or two R on the same atom form an oxo.

5. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: RY1is hydrogen, C1-C6alkyl, or C1-C6haloalkyl.

6. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: RY1is C1-C6alkyl independently optionally substituted with one or more R.

7. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: RY1is C1-C6alkyl.

8. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: RY1is ethyl.

9. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: RY1is -CD2CD3or -CH2CH2OCD3.

10. A compound of Formula (IXb), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:wherein: R30is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; R31is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, - L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X is -O-, -S-, -NR32-, or -C(R33)2-; R32is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2- C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each R33is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;each Z is independently N or CR2; each R2is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, C1- C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2- C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each R3is independently hydrogen, halogen, -CN, C1-C6alkyl, or C1-C6haloalkyl; wherein each alkyl is independently optionally substituted with one or more R; R6is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; X3is N or CR7; R7is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein the alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; Ring B is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; each R8is independently halogen, -CN, -NO2, -OH, -ORa, -OC(=O)Ra, -OC(=O)ORb, -OC(=O)NRcRd, - SF5, -SH, -SRa, -S(=O)Ra, -S(=O)2Ra, -S(=O)2NRcRd, -S(=NRb)(=O)Rb, -NRcRd, -NRbC(=O)NRcRd, - NRbC(=O)Ra, -NRbC(=O)ORb, -NRbS(=O)2Ra, -P(=O)(Rb)2, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; m is 0, 1, 2, 3, or 4; each Rais independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rbis independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L- heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; each Rcand Rdare independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, -L-cycloalkyl, -L-heterocycloalkyl,-L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more R; L is absent or C1-C3alkylene independently optionally substituted with one or more R; and each R is independently halogen, -CN, -OH, -S(=O)C1-C3alkyl, -S(=O)2C1-C3alkyl, -S(=O)2NH2, - S(=O)2NHC1-C3alkyl, -S(=O)2N(C1-C3alkyl)2, -NH2, -NHC1-C3alkyl, -N(C1-C3alkyl)2, -C(=O)C1- C3alkyl, -C(=O)OH, -C(=O)OC1-C3alkyl, -C(=O)NH2, -C(=O)NHC1-C3alkyl, -C(=O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, C3-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; and / or two R on the same atom form an oxo.

11. The compound of claim 10, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: each R3is independently hydrogen or C1-C6alkyl.

12. The compound of any one of claims 1-11, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: X3is N.

13. The compound of any one of claims 1-11, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: X3is CR7.

14. The compound of any one of claims 1-13, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: R30is -CH3.

15. The compound of any one of claims 1-13, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: R30is -CD3.

16. The compound of any one of claims 1-15, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: R31is hydrogen, -CN, C1-C6alkyl, C1-C6hydroxyalkyl, or -L-cycloalkyl.

17. The compound of any one of claims 1-16, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: R31is -CN or C1-C6alkyl.

18. The compound of any one of claims 1-17, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: R31is C1-C6alkyl.

19. The compound of any one of claims 1-18, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein:.

20. The compound of any one of claims 1-19, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein:.

21. The compound of claim 20, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: Z is CR2.

22. The compound of claim 20, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: Z is N.

23. The compound of any one of claims 1-21, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: each R2is independently hydrogen or halogen.

24. The compound of any one of claims 1-21, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: each R2is hydrogen.

25. The compound of any one of claims 1-24, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: R7is hydrogen, halogen, or C1-C6alkyl.

26. The compound of any one of claims 1-25, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: R7is hydrogen.

27. The compound of any one of claims 1-26, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: R6is hydrogen, halogen, or C1-C6haloalkyl.

28. The compound of any one of claims 1-27, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: R6is C1-C6alkyl.

29. The compound of any one of claims 1-28, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: Ring B is phenyl.

30. The compound of any one of claims 1-29, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: each R8is independently halogen or -C(=O)NRcRd.

31. The compound of any one of claims 1-29, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: each R8is independently -C(=O)NRcRd.

32. The compound of any one of claims 1-29, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: each R8is independently halogen or -C(=O)NH(heteroaryl); wherein the heteroaryl is independently optionally substituted with one or more R.

33. The compound of any one of claims 1-29, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: each R8is independently halogen or heteroaryl; wherein each heteroaryl is independently optionally substituted with one or more R.

34. The compound of any one of claims 1-33, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: m is 1 or 2.

35. The compound of any one of claims 1-33, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: m is 1.

36. The compound of any one of claims 1-30, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein:

37. The compound of any one of claims 1-30, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein:

38. The compound of any one of claims 1-30, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein:

39. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: one or more hydrogen has been replaced by a deuterium.

40. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: three hydrogens have been replaced by a deuterium.

41. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: five hydrogens have been replaced by a deuterium.

42. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: one or more hydrogen in R30has been replaced by a deuterium.

43. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: one or more hydrogen in R31has been replaced by a deuterium.

44. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: one or more hydrogen in RY1has been replaced by a deuterium.

45. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: one or more hydrogen in R3has been replaced by a deuterium.

46. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof; wherein: one or more hydrogen in R8has been replaced by a deuterium.

47. A compound selected from a compound found in table 1 or in the specification, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

48. A pharmaceutical composition comprising a compound of any one of claims 1-47, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, and a pharmaceutically acceptable excipient.

49. A method of treating a disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of any one of claims 1-47, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, or the pharmaceutical composition of claim 48.

50. The method of claim 49, wherein the disorder in alopecia, aspergillus, asthma, atomic dermatitis, chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis with nasal polyposis, gastritis, inflammatory bowel disease, pemphigoid, prurigo nodularis, sinusitis, or urticaria.

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