PI3Kα Inhibitor and Method of Using the Same

Abstract

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of the PI3Kα enzyme using the compounds and compositions of the present disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with PI3Kα signaling using the compounds and compositions of the present disclosure. Inhibitors of PI3Kα are considered to be particularly valuable in the treatment of proliferative diseases and other disorders. A plurality of inhibitors of PI3K (for example, taselisib, alpelisib, buparlisib, etc.) have been developed, but these molecules inhibit multiple class 1A PI3K isoforms.

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims the benefit of U.S. Provisional Application No. 63 / 364,459, filed May 10, 2022, the entire disclosure of which is hereby incorporated by reference herein.

Background Art

[0002] Phosphatidylinositol 3-kinase (PI3K) is a family of lipid kinases that catalyze the transfer of phosphate to the D-3’ position of inositol lipids to generate phosphatidylinositol-3-phosphate (PIP), phosphatidylinositol-3,4-bisphosphate (PIP2), and phosphatidylinositol-3,4,5-trisphosphate (PIP3), which in turn function as second messengers in signal transduction cascades by often docking proteins containing pleckstrin homology, FYVE, Phox, and other phospholipid-binding domains to various signal transduction complexes at the cell membrane (Vanhaesebroeck et al., Annu. Rev. Biochem 70:535 (2001); Katso et al., Annu. Rev. Cell Dev. Biol. 17:615 (2001)). Of the two class 1 PI3K subclasses, class 1A PI3K is a heterodimer composed of a catalytic p110 subunit (alpha, beta, or delta isoform) constitutively associated with a regulatory subunit that can be p85 alpha, p55 alpha, p50 alpha, p85 beta, or p55 gamma. The class 1B subclass has one family member, a heterodimer composed of a catalytic p110 gamma subunit bound to one of two regulatory subunits, p101 or p84 (Fruman et al., Annu Rev. Biochem. 67:481 (1998); Suire et al., Curr. Biol. 15:566 (2005)). The modular domains of the p85 / 55 / 50 subunits contain Src homology (SH2) domains that bind to phosphotyrosine residues in specific sequence contexts on activated receptors and cytoplasmic tyrosine kinases, resulting in the activation and localization of class 1A PI3K. Class 1B PI3K is directly activated by G protein-coupled receptors that bind a diverse repertoire of peptide and non-peptide ligands (Stephens et al., Cell 89:105 (1997); Katso et al., Annu. Rev. Cell Dev. Biol. 17:615-675 (2001)).

[0003] As a result, the lipid products of class I PI3K link upstream receptors to downstream cellular activities including proliferation, survival, chemotaxis, cell transport, motility, metabolism, inflammatory and allergic responses, transcription, and translation (Cantley et al., Cell 64:281 (1991); Escobedo and Williams, Nature 335:85 (1988); Fantl et al., Cell 69:413 (1992)). In many cases, PIP2 and PIP3 recruit Akt, the product of the human homolog of the viral oncogene v-Akt, to the cell membrane, where it functions as a nodal point for many intracellular signaling pathways important for growth and survival (Fantl et al., Cell 69:413-423 (1992); Bader et al., Nature Rev. Cancer 5:921 (2005); Vivanco and Sawyer, Nature Rev. Cancer 2:489 (2002)).

[0004] Aberrant regulation of PI3K often enhances survival by activation of Aid, which is one of the most common events in human cancers and has been shown to occur at multiple levels. The tumor suppressor gene PTEN, which dephosphorylates phosphoinositides at the 3’ position of the inositol ring and thereby antagonizes PI3K activity, is functionally deleted in various tumors. In other tumors, the genes for the p110 alpha isoform, PIK3CA, and the Akt gene are amplified, and increased protein expression of their gene products has been demonstrated in some human cancers. In addition, mutations and translocations of p85 alpha that serve to upregulate the p85-p110 complex have been reported in human cancers. Finally, somatic missense mutations in PIK3CA that activate downstream signaling pathways have been reported at significant frequencies in various human cancers (Kang et el., Proc. Natl. Acad. Sci. USA 102:802(2005); Samuels et al., Science 304:554(2004); Samuels et al., Cancer Cell 7:561-573(2005)). These observations indicate that dysregulation of phosphoinositide-3 kinase and upstream and downstream components of this signaling pathway is one of the most common dysregulations associated with human cancers and proliferative diseases (Parsons et al., Nature 436:792(2005); Hennessey at el., Nature Rev. Drug Disc.4:988-1004(2005)). Considering the above, inhibitors of PI3Kα are considered to be particularly valuable in the treatment of proliferative diseases and other disorders. Multiple inhibitors of PI3K (e.g., taselisib, alpelisib, buparlisib, etc.) have been developed, and these molecules inhibit multiple class 1A PI3K isoforms. Inhibitors that are active against multiple class 1A PI3K isoforms are known as "pan-PI3K" inhibitors. A major obstacle in the clinical development of conventional PI3K inhibitors is the inability to achieve the required level of target inhibition in tumors while avoiding toxicity in cancer patients. Pan-PI3K inhibitors share certain target-related toxicities such as diarrhea, rash, fatigue, and hyperglycemia. The toxicity of PI3K inhibitors depends on their isoform selectivity profiles. Inhibition of PI3Kα is associated with hyperglycemia and rash, and inhibition of PI3Kδ or PI3Kγ is associated with diarrhea, myelosuppression, and hypertransaminasemia (Hanker et al., Cancer Discovery (2019) PMID: 30837161). Therefore, selective inhibitors of PI3Kα may enable sufficient target inhibition within tumors while avoiding dose-limiting toxicity in cancer patients and expanding the therapeutic window.

Prior Art Documents

Non-Patent Documents

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Summary of the Invention

[0006] In some embodiments, the present disclosure provides a compound of Formula I:

Chemical Formula

[0007] In some embodiments, the present disclosure provides a pharmaceutical composition comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or diluent.

[0008] In some embodiments, the present disclosure provides a method of treating a PI3Kα-mediated disorder, the method comprising administering to a patient in need thereof a compound of formula I, or a composition comprising the compound.

[0009] In some embodiments, the present disclosure provides a process for providing a compound of formula I, or a synthetic intermediate thereof.

[0010] In some embodiments, the present disclosure provides a process for providing a pharmaceutical composition comprising a compound of formula I. **DETAILED DESCRIPTION OF THE INVENTION**

[0011] 1. Overview of Certain Embodiments of the Present Disclosure The compounds of the present disclosure and their pharmaceutical compositions are useful as inhibitors of PI3Kα. In some embodiments, the present disclosure provides a compound of formula I: **CHEMICAL STRUCTURE** or a pharmaceutically acceptable salt thereof, wherein Cy 1 is phenyl; naphthyl; cubanyl; adamantyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Cy 1 is substituted with n R 1 and Cy 2is phenyl; naphthyl; cubanyl; adamantyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Cy 2 is substituted with m R 2 s, Q is L Q ; T is a divalent C T aliphatic chain substituted with q R 1-3 s, each R 1 is independently -L 1 -R 1A ; each R 2 is independently -L 2 -R 2A ; each R T is independently -L T -R TA or two of the R T s together with their intervening atoms form a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is substituted with p 1 R TTC s, two of the R 1 s together with their intervening atoms form a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is substituted with p 2 R11C is replaced by R 2 Two of them, together with their intervening atoms, form a 3- to 7-membered saturated, partially unsaturated or aromatic carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is substituted with p 3 R groups 22C is replaced by R T One of and 1 One of form, together with their intervening atoms, a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is substituted with p 4 R groups T1C is replaced by, or R T One of and L One of form, together with their intervening atoms, a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is substituted with p 5 R groups TLC is replaced by L 1 L 2 L Q and T Each of is independently a covalent bond or a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-4 wherein one or two methylene units of the chain are optionally and independently -CH(R L )-, -C(R L )2-, C 3-6 cycloalkylene, C 3-6is replaced by a heterocycloalkylene, -N(R)-, -N(R)C(O)-, -N(R)C(NR)-, -N(R)C(NOR)-, -N(R)C(NCN)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-; each R 1A is independently r 1 R's 1C substituted by R A or R B and each R 2A is independently r 2 R's 2C substituted by R A or R B and each R TA is independently r 3 R's TC substituted by R A or R B and each R L is independently r 4 R's LC substituted by R A or R B and each R A is independently oxo, deuterium, halogen, -CN, -NO2, -OR, -SF5, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -S(O)(NCN)R, -S(NCN)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2; each R B is independently C 1-6an aliphatic chain; phenyl; naphthyl; cubanyl; adamantyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, R 1C 、R 2C 、R TC 、R TTC 、R 11C 、R 22C 、R T1C 、R TLC 、and R LC each of which is independently oxo, deuterium, halogen, -CN, -NO2, -OR, -SF5, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, or C 1-6 an optionally substituted group selected from aliphatic, phenyl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of R is independently hydrogen, or C 1-6A group optionally substituted and selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or Two R groups on the same nitrogen, together with their intervening atoms, form, in addition to said nitrogen, a 4- to 7-membered saturated ring, partially unsaturated ring, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, n, m, q, p 1 , p 2 , p 3 , p 4 , p 5 , r 1 , r 2 , r 3 , and r 4 Each of which is independently 0, 1, 2, 3, 4, or 5.

[0012] 2. Compounds and Definitions The compounds of the present disclosure include those outlined herein and are further exemplified by the classes, subclasses, and species disclosed herein. As used herein, unless otherwise specified, the following definitions apply. For the purposes of the present disclosure, chemical elements are identified according to the CAS version of the Periodic Table of the Elements (Handbook of Chemistry and Physics, 75 th Ed). In addition, the general principles of organic chemistry are described in “Organic Chemistry”, Thomas Sorrell, University Science Books, Sausalito: 1999, and “March’s Advanced Organic Chemistry”, 5 th Ed., Ed.: Smith, M.B. and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are incorporated herein by reference.

[0013] As used herein, the term "aliphatic" or "aliphatic group" means a straight-chain (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain that has one point of attachment to the remainder of the molecule and is either completely saturated or contains one or more units of unsaturation, or a monocyclic or bicyclic hydrocarbon that is either completely saturated or contains one or more units of unsaturation but is not aromatic (also referred to herein as a "carbocycle" or "cycloaliphatic"). Unless otherwise specified, an aliphatic group contains from 1 to 6 aliphatic carbon atoms. In some embodiments, the aliphatic group contains from 1 to 5 aliphatic carbon atoms. In other embodiments, the aliphatic group contains from 1 to 4 aliphatic carbon atoms. In still other embodiments, the aliphatic group contains from 1 to 3 aliphatic carbon atoms, and in still other embodiments, the aliphatic group contains from 1 to 2 aliphatic carbon atoms. In some embodiments, "cycloaliphatic" (or "carbocycle") refers to a monocyclic C3-C6 hydrocarbon that has one point of attachment to the remainder of the molecule and is either completely saturated or contains one or more units of unsaturation but is not aromatic. Suitable aliphatic groups include, but are not limited to, linear or branched, substituted or unsubstituted alkyl groups, alkenyl groups, alkynyl groups, and their hybrids such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl.

[0014] As used herein, the term "alkyl" refers to a monovalent aliphatic hydrocarbon radical having a straight-chain, branched-chain, monocyclic moiety, or polycyclic moiety or combinations thereof, where the radical is optionally substituted at one or more carbons of the straight-chain, branched-chain, monocyclic moiety, or polycyclic moiety or combinations thereof, and one or more substituents are independently C1-C 10It is alkyl. Examples of the "alkyl" group include methyl, ethyl, propyl, isopropyl, butyl, iso-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl, and the like.

[0015] The term "lower alkyl" refers to a straight-chain or branched alkyl group of C 1-4 Exemplary lower alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl.

[0016] The term "lower haloalkyl" refers to a straight-chain or branched alkyl group of C 1-4 substituted with one or more halogen atoms.

[0017] The term "heteroatom" means one or more of oxygen, sulfur, nitrogen, phosphorus, or silicon (any oxidation form of nitrogen, sulfur, phosphorus, or silicon; any quaternized form of any basic nitrogen; or a substitutable nitrogen in a heterocyclic ring, such as that in N(3,4-dihydro-2H-pyrrolyl), NH (in pyrrolidinyl), or NR + (in N-substituted pyrrolidinyl)).

[0018] As used herein, the term "unsaturated" means that the moiety has one or more unsaturated units.

[0019] As used herein, the term "a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-8 (or C 1-6 , or C 1-4 )" refers to a divalent alkylene chain, alkenylene chain, and alkynylene chain that are straight-chain or branched as defined herein.

[0020] The term "alkylene" refers to a divalent alkyl group. An "alkylene chain" is a polymethylene group, i.e., -(CH2)n - and in the formula, n is a positive integer, preferably 1 to 6, 1 to 4, 1 to 3, 1 to 2, or 2 to 3. The substituted alkylene chain is a polymethylene group in which one or more methylene hydrogen atoms are replaced by substituents. Suitable substituents include those described below for substituted aliphatic groups.

[0021] The term "alkenylene" refers to a divalent alkenyl group. The substituted alkenylene chain is a polymethylene group containing at least one double bond in which one or more hydrogen atoms are replaced by substituents. Suitable substituents include those described below for substituted aliphatic groups.

[0022] The term "halogen" means F, Cl, Br, or I.

[0023] The term "aryl", used alone or as part of a larger moiety such as "aralkyl", "aralkoxy", or "aryloxyalkyl", refers to a monocyclic or bicyclic ring system having a total of 5 to 14 ring members, wherein at least one ring in the system is aromatic and each ring in the system contains 3 to 7 ring members. The term "aryl" can be used interchangeably with the term "aryl ring". In certain embodiments of the present disclosure, "aryl" refers to an aromatic ring system including, but not limited to, phenyl, biphenyl, naphthyl, anthracyl, etc., and may have one or more substituents.

[0024] The term "heteroaryl" or "heterocyclic aromatic", as used herein unless otherwise defined, refers to a 5- to 6-membered monocyclic aromatic ring containing one or more heteroatoms such as nitrogen, oxygen, and sulfur, e.g., 1 to 3 heteroatoms, or an 8- to 10-membered polycyclic ring system containing one or more heteroatoms, wherein at least one ring in the polycyclic ring system is aromatic and the point of attachment of the polycyclic ring system is through a ring atom on the aromatic ring. The heteroaryl ring may be linked to adjacent radicals through carbon or nitrogen. Examples of heteroaryl include, but are not limited to, furan, thiophene, pyrrole, thiazole, oxazole, isothiazole, isoxazole, imidazole, pyrazole, triazole, pyridine, pyrimidine, indole, etc. For example, unless otherwise defined, 1,2,3,4-tetrahydroquinoline is a heteroaryl ring when its point of attachment is through the benzo ring, as follows: [Chemical formula]

[0025] The term "heterocyclyl" or "heterocyclic group", as used herein unless otherwise defined, refers to a saturated or partially unsaturated 3- to 10-membered monocyclic or 7- to 14-membered polycyclic ring system, including bridged or fused rings, and the ring system contains 1 to 4 heteroatoms such as nitrogen, oxygen, and sulfur. The heterocyclyl ring may be linked to adjacent radicals through carbon or nitrogen.

[0026] The term "partially unsaturated" in the context of a ring, unless otherwise defined, refers to a monocyclic ring or a constituent ring within a polycyclic (e.g., bicyclic, tricyclic, etc.) ring system that contains at least one degree of unsaturation in addition to the degree of unsaturation provided by the ring itself and is not aromatic. Examples of partially unsaturated rings include, but are not limited to, 3,4-dihydro-2H-pyran, 3-pyrroline, 2-thiazoline, etc. When a partially unsaturated ring is part of a polycyclic ring system, the other constituent rings in the polycyclic ring system may be saturated, partially unsaturated, or aromatic, provided that the point of attachment of the polycyclic ring system is on the partially unsaturated constituent ring. For example, unless otherwise defined, 1,2,3,4-tetrahydroquinoline is a partially unsaturated ring when, for example, its point of attachment is through the piperidino ring as follows:

Chem.

[0027] The term "saturated" in the context of a ring, unless otherwise defined, refers to a monocyclic ring of 3 to 10 members or a polycyclic (e.g., bicyclic, tricyclic, etc.) ring system of 7 to 14 members, where the constituent ring that is the point of attachment of the monocyclic or polycyclic ring system has no additional degree of unsaturation in addition to the degree of unsaturation provided by the ring itself. Examples of monocyclic saturated rings include, but are not limited to, azetidine, oxetane, cyclohexane, etc. When a saturated ring is part of a polycyclic ring system, the other constituent rings in the polycyclic ring system may be saturated, partially unsaturated, or aromatic, provided that the point of attachment of the polycyclic ring system is on the unsaturated constituent ring. For example, unless otherwise defined, 2-azaspiro[3.4]oct-6-ene is a saturated ring when, for example, its point of attachment is through the azetidine ring as follows:

Chem.

[0028] As used herein, the terms "alkylene", "arylene", "cycloalkylene", "heteroarylene", "heterocycloalkylene", and other similar terms containing the suffix "-ylene" refer to the divalent bond type of the group modified by the suffix. For example, "alkylene" is a divalent alkyl group that connects the groups to which the said group is bonded.

[0029] As used herein, the term "bridged bicyclic" refers to any saturated or partially unsaturated bicyclic ring system having at least one bridge, i.e., a carbocyclic or heterocyclic ring system. According to the IUPAC definition, a "bridge" is an unbranched chain or valence bond of one or more atoms connecting two bridgeheads, and a "bridgehead" is any skeletal atom of a ring system that is bonded to three or more skeletal atoms (excluding hydrogen). In some embodiments, the bridged bicyclic group has 7 to 12 ring members and 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Such bridged bicyclic groups are well known in the art and include the groups described below, where each group is bonded to the rest of the molecule at any substitutable carbon or nitrogen atom. Unless otherwise specified, the bridged bicyclic group is optionally substituted with one or more substituents as described for aliphatic groups. Alternatively or additionally, the substitutable nitrogen of the bridged bicyclic group is optionally substituted. Exemplary bridged bicyclics include the following:

Chemical formula

[0030] As described herein, the compounds of the present disclosure may contain "optionally substituted" moieties. In general, the term "substituted", whether or not preceded by the term "optionally", means that one or more hydrogens of the designated moiety are replaced by a suitable substituent. Unless otherwise specified, an "optionally substituted" group may have a suitable substituent at each substitutable position of the group, and two or more positions of any given structure may be substituted with two or more substituents selected from a particular group, and the substituents may be the same or different at each position. The combinations of substituents contemplated by the present disclosure are preferably substituents that result in the formation of stable or chemically feasible compounds. As used herein, the term "stable" refers to a compound that does not substantially change even when subjected to the conditions that allow for the production, detection, and in certain embodiments, the recovery, purification, and use of the compound for one or more of the purposes disclosed herein.

[0031] Suitable monovalent substituents on a substitutable carbon atom of an "optionally substituted" group are, independently, halogen; -(CH2) 0-4 R°; -(CH2) 0-4 OR°; -O(CH2) 0-4 R o , -O-(CH2) 0-4 C(O)OR°; -(CH2) 0-4 CH(OR°)2; -(CH2) 0-4 SR°; -(CH2) 0-4 Ph (which may be substituted with R°); -(CH2) 0-4 O(CH2) 0-1 Ph (which may be substituted with R°); -CH=CHPh (which may be substituted with R°); -(CH2) 0-4 O(CH2) 0-1 -pyridyl (which may be substituted with R°); -NO2; -CN; -N3; -(CH2) 0-4 N(R°)2; -(CH2) 0-4 N(R°)C(O)R°; -N(R°)C(S)R°; -(CH2) 0-4 N(R°)C(O)NR°2; -N(R°)C(S)NR°2; -(CH2) 0-4N(R°)C(O)OR°; -N(R°)N(R°)C(O)R°; -N(R°)N(R°)C(O)NR°2; -N(R°)N(R°)C(O)OR°; -(CH2) 0-4 C(O)R°; -C(S)R°; -(CH2) 0-4 C(O)OR°; -(CH2) 0-4 C(O)SR°; -(CH2) 0-4 C(O)OSiR°3; -(CH2) 0-4 OC(O)R°; -OC(O)(CH2) 0-4 SR°; -SC(S)SR°; -(CH2) 0-4 SC(O)R°; -(CH2) 0-4 C(O)NR°2; -C(S)NR°2; -C(S)SR°; -SC(S)SR°, -(CH2) 0-4 OC(O)NR°2; -C(O)N(OR°)R°; -C(O)C(O)R°; -C(O)CH2C(O)R°; -C(NOR°)R°; -(CH2) 0-4 SSR°; -(CH2) 0-4 S(O)2R°; -(CH2) 0-4 S(O)2OR°; -(CH2) 0-4 OS(O)2R°; -S(O)2NR°2; -(CH2) 0-4 S(O)R°; -N(R°)S(O)2NR°2; -N(R°)S(O)2R°; -N(OR°)R°; -C(NH)NR°2; -P(O)(OR°)R°; -P(O)R°2; -OP(O)R°2; -OP(O)(OR°)2; -SiR°3; -(C 1-4 linear or branched alkylene)O-N(R°)2; or -(C 1-4 linear or branched alkylene)C(O)O-N(R°)2, wherein each R° may be substituted as defined below and is independently hydrogen, C 1-6 aliphatic, -CH2Ph, -O(CH2) 0-1Ph, -CH2-(a 5- or 6-membered heteroaryl ring), or a 5- or 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, regardless of the above definition, two independently occurring R°s together with the intervening atom(s) form a 3- to 12-membered saturated, partially unsaturated, or aryl monocyclic or bicyclic ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and may be substituted as defined below.

[0032] Suitable monovalent substituents on R° (or the ring formed by two independently occurring R°s together with the intervening atom) are, independently, halogen, -(CH2) 0-2 R ● , -(haloR ● ), -(CH2) 0-2 OH, -(CH2) 0-2 OR ● , -(CH2) 0-2 CH(OR ● ), -O(haloR ● ), -CN, -N3, -(CH2) 0-2 C(O)R ● , -(CH2) 0-2 C(O)OH, -(CH2) 0-2 C(O)OR ● , -(CH2) 0-2 SR ● , -(CH2) 0-2 SH, -(CH2) 0-2 NH2, -(CH2) 0-2 NHR ● , -(CH2) 0-2 NR ● 2, -NO2, -SiR ● 3, -OSiR ● 3, -C(O)SR ● 、 -(C 1-4 linear or branched alkylene)C(O)OR ● , or -SSR ● , wherein each R ● is unsubstituted or, if preceded by "halo", is substituted only by one or more halogens, C1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph, or a 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents on the saturated carbon atoms of R° include =O and =S.

[0033] Suitable divalent substituents on the saturated carbon atoms of a "optionally substituted" group include the following: =O, =S, =NNR * 2, =NNHC(O)R * , =NNHC(O)OR * , =NNHS(O)2R * , =NR * , =NOR * , -O(C(R * 2)) 2-3 O-, or -S(C(R * 2)) 2-3 S- (where each R independently appearing * is hydrogen, C that may be substituted as defined below 1-6 aliphatic, or selected from an unsubstituted 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur). Suitable divalent substituents bonded to the vicinal substitutable carbons of a "optionally substituted" group include the following: -O(CR * 2) 2-3 O- (where each R independently appearing * is hydrogen, C that may be substituted as defined below 1-6 aliphatic, or selected from an unsubstituted 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur).

[0034] R * Suitable substituents on the aliphatic groups of include halogen, -R ● , -(haloR ● ), -OH, -OR ● , -O(haloR ● ), -CN, -C(O)OH, -C(O)OR● 、 -NH2, -NHR ● 、 -NR ● 2, or -NO2 is included, wherein each R ● is unsubstituted or, if preceded by "halo", is substituted only by one or more halogens and independently is C 1-4 aliphatic, -CH2Ph, -O(CH2) 0-1 Ph, or a 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0035] Suitable substituents on the nitrogen of the "optionally substituted" group include -R † 、 -NR † 2, -C(O)R † 、 -C(O)OR † 、 -C(O)C(O)R † 、 -C(O)CH2C(O)R † 、 -S(O)2R † 、 -S(O)2NR † 2, -C(S)NR † 2, -C(NH)NR † 2, or -N(R † )S(O)2R † is included, wherein each R † is independently hydrogen, C 1-6 aliphatic which may be substituted as defined below, unsubstituted -OPh, or an unsubstituted 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, regardless of the above definition, two independently occurring R † together with the intervening atom(s) form an unsubstituted 3- to 12-membered saturated, partially unsaturated, or aryl monocyclic or bicyclic ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0036] R † Suitable substituents on the aliphatic group of are independently halogen, -R ● 、 -(haloR ● )、 -OH, -OR ●, -O(halo R ● ), -CN, -C(O)OH, -C(O)OR ● , -NH2, -NHR ● , -NR ● 2, or -NO2, wherein each R ● is unsubstituted or, if preceded by "halo", is substituted only with one or more halogens and, independently, is C 1-4 aliphatic, -CH2Ph, -O(CH2) 0-1 Ph, or a 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0037] As used herein, the term "isomer" refers to compounds having the same chemical formula but different structural or optical arrangements. As used herein, the term "stereoisomer" refers to isomeric molecules having the same molecular formula but different spatial positions of atoms and / or functional groups and includes them. All stereoisomers of the compounds herein, including enantiomeric and diastereomeric forms (e.g., those that may exist due to asymmetric carbons on various substituents), are intended to be within the scope of this disclosure. Accordingly, unless otherwise specified, not only one stereochemical isomer of the compounds herein, but also mixtures of enantiomers, diastereomers, and geometric isomers (or conformational isomers) are within the scope of this disclosure.

[0038] As used herein, the term "tautomer" refers to one of two or more structural isomers that exist in equilibrium and are readily convertible from one isomeric form to another. It is understood that tautomers include valence tautomers and proton tautomers (also known as prototropic tautomers). Valence tautomers involve interconversion through partial rearrangement of bonding electrons. Proton tautomers involve interconversion through the movement of protons such as keto-enol and imine-enamine isomerization. Unless otherwise specified, all tautomers of the compounds of this disclosure are within the scope of this disclosure.

[0039] As used herein, the term "isotopic substitution" refers to replacing an atom with its isotope. As used herein, the term "isotope" refers to an atom having the same atomic number as the preponderant atom in nature but a different mass number (number of neutrons) from the preponderant atom in nature. It is understood that a compound having isotopic substitution refers to a compound in which at least one atom contained in the compound is replaced with its isotope. Atoms that can be substituted with isotopes include, but are not limited to, hydrogen, carbon, and oxygen. Examples of isotopes of the hydrogen atom include 2 H (also denoted as D) and 3 H. Examples of isotopes of the carbon atom include 13 C and 14 C. Examples of isotopes of the oxygen atom include 18 O. Unless otherwise specified, all isotopic substitutions of the compounds of the present disclosure are within the scope of the present disclosure. Such compounds are useful, for example, as analytical tools, probes for biological assays, or therapeutic agents according to the present disclosure.

[0040] As used herein, the term "pharmaceutically acceptable salt" represents a salt suitable for use in contact with the tissues of humans and lower animals within the scope of sound medical judgment, without undue toxicity, irritation, allergic response, etc., and commensurate with a reasonable benefit / risk ratio. Exemplary pharmaceutically acceptable salts are found, for example, in Berge, et al. (J. Pharm. Sci. 1977, 66(1), 1; and Gould, P. L., Int. J. Pharmaceutics 1986, 33, 201-217; each of which is incorporated herein by reference in its entirety).

[0041] Pharmaceutically acceptable salts of the compounds of the present disclosure include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable non-toxic acid addition salts are inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid, or organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid, or salts of amino groups formed by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, etc.

[0042] Salts derived from suitable bases include alkali metal salts, alkaline earth metal salts, ammonium salts, and N + (C 1-4 alkyl)4 salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, etc. Further pharmaceutically acceptable salts include non-toxic ammonium, quaternary ammonium, and amine cations formed by using counterions such as halides, hydroxides, carboxylic acids, sulfuric acid, phosphoric acid, nitric acid, lower alkyl sulfonic acids, and aryl sulfonic acids where appropriate.

[0043] Pharmaceutically acceptable salts are also intended to include hemisalts in which the compound:acid ratio is 2:1 respectively. Exemplary hemisalts are salts derived from acids containing two carboxylic acid groups such as malic acid, fumaric acid, maleic acid, succinic acid, tartaric acid, glutaric acid, oxalic acid, adipic acid and citric acid. Other exemplary hemisalts are salts derived from dibasic mineral acids such as sulfuric acid. Exemplary preferred hemisalts include, but are not limited to, hemimaleate, hemifumarate, and hemisuccinate.

[0044] As used herein, the term "about" is used to mean approximately, roughly, around, or within that range. When the term "about" is used with a numerical range, the range is modified by expanding the boundaries above and below the recited numerical values. Generally, the term "about" is used herein to modify the numerical values above and below the specified value with a variability of plus or minus 20%.

[0045] As used herein, "effective amount", "sufficient amount", or "therapeutically effective amount" is an amount of a compound sufficient to produce a beneficial or desired result, including clinical results. Thus, an effective amount may be sufficient, for example, to reduce or improve the severity and / or duration of pain associated with PI3Kα signaling or one or more of its symptoms, to prevent the progression of a condition or symptom associated with pain associated with PI3Kα signaling, or to enhance or otherwise improve the prophylactic or therapeutic effect(s) of another treatment. An effective amount also includes an amount of a compound that avoids or substantially attenuates undesirable side effects.

[0046] As used herein and as is well understood in the art, "treatment" is an approach for obtaining beneficial or desired results, including clinical results. Beneficial or desired clinical results can include, but are not limited to, alleviation or improvement of one or more symptoms or conditions, whether detectable or undetectable, reduction in the degree of a disease or affliction, a stabilized (i.e., not worsening) disease or affliction state, prevention of spread of a disease or affliction, delay or slowing of progression of a disease or affliction, improvement or temporary relief and remission (whether partial or complete) of a disease or affliction state. "Treatment" can also mean extending the survival period as compared to the expected survival period without receiving treatment. In some embodiments, treatment can be performed after one or more symptoms have manifested. In other embodiments, treatment may be administered in the absence of symptoms. For example, treatment may be performed on an individual susceptible to a disease prior to the manifestation of symptoms (e.g., in light of a history of symptoms and / or genetic or other susceptibility factors). Treatment can also be continued after symptoms have disappeared, for example, to prevent or delay recurrence.

[0047] The phrase "in need thereof" refers to the need for symptomatic or asymptomatic alleviation from a condition associated with PI3Kα signaling activity or a condition that can otherwise be resolved by the compounds and / or compositions of the present disclosure.

[0048] 3. Description of Exemplary Embodiments As described above, in some embodiments, the present disclosure provides a compound of Formula I: [Chemical Structure] or a pharmaceutically acceptable salt thereof, wherein Cy 1is phenyl; naphthyl; cubanyl; adamantyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 1 is substituted with n R 1 s, Cy 2 is phenyl; naphthyl; cubanyl; adamantyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 2 is substituted with m R 2 s, Q is L Q and T is a divalent C T aliphatic chain substituted with q R 1-3 s, each R 1 is independently -L 1 -R 1A and each R 2 is independently -L 2 -R 2A or each R T is independently -L T -R TA or R TTwo of them, together with their intervening atoms, form a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is substituted with p 1 number of R TTC and R 1 Two of them, together with their intervening atoms, form a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is substituted with p 2 number of R 11C and R 2 Two of them, together with their intervening atoms, form a 3- to 7-membered saturated, partially unsaturated or aromatic carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is substituted with p 3 number of R 22C and R T One of and R 1 One of them, together with their intervening atoms, form a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is substituted with p 4 number of R T1C or R T One of and R L One of them, together with their intervening atoms, form a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is substituted with p 5 number of R TLC and L 1 L 2 L Q and L T Each of is independently a covalent bond or C1-4 is a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain, where one or two methylene units of the chain are optionally and independently replaced by -CH(R L ), -C(R L )2-, C 3-6 cycloalkylene, C 3-6 heterocycloalkylene, -N(R)-, -N(R)C(O)-, -N(R)C(NR)-, -N(R)C(NOR)-, -N(R)C(NCN)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-, each R 1A is independently R 1 substituted by r 1C R A or R B , each R 2A is independently R 2 substituted by r 2C R A or R B , each R TA is independently R 3 substituted by r TC R A or R B , each R L is independently R 4 substituted by r LC R A or R B , R AEach of which is independently oxo, deuterium, halogen, -CN, -NO2, -OR, -SF5, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -S(O)(NCN)R, -S(NCN)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2, R B each of which is independently C 1-6 an aliphatic chain; phenyl; naphthyl; cubanyl; adamantyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, R 1C R 2C R TC R TTC R 11C R 22C R T1C R TLC and R LCEach of which is independently oxo, deuterium, halogen, -CN, -NO2, -OR, -SF5, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, or C 1-6 A group optionally substituted and selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur Each of R is independently hydrogen, or C 1-6 A group optionally substituted and selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or Two R groups on the same nitrogen, together with their intervening atoms, form, in addition to said nitrogen, a 4- to 7-membered saturated ring, partially unsaturated ring, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur n, m, q, p 1 , p 2 , p 3 , p 4 , p 5 , r 1 , r 2 , r 3 , and r 4 Each of which is independently 0, 1, 2, 3, 4, or 5

[0049] As defined generally above, Cy 1is phenyl; naphthyl; cubanyl; adamantyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Cy 1 is n R 1 substituted.

[0050] In some embodiments, Cy 1 is phenyl, wherein Cy 1 is n R 1 substituted. In some embodiments, Cy 1 is naphthyl, wherein Cy 1 is n R 1 substituted. In some embodiments, Cy 1 is cubanyl, wherein Cy 1 is n R 1 substituted. In some embodiments, Cy 1 is adamantyl, wherein Cy 1 is n R 1 substituted. In some embodiments, Cy 1 is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, wherein Cy 1 is n R 1 substituted. In some embodiments, Cy 1 is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Cy 1 is n R 1 substituted. In some embodiments, Cy 1 is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Cy 1 is n R 1is replaced. In some embodiments, Cy 1 is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 1 is substituted with n R 1 .

[0051] In some embodiments, Cy 1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0052] In some embodiments, Cy 1 is

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

[0053] In some embodiments, Cy 1 is [Chemical formula] wherein R 1 is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, Cy 1 is [Chemical formula] wherein R 1 is a halogen. In some embodiments, Cy 1 is [Chemical formula] In some embodiments, Cy 1 is [Chemical formula] In some embodiments, Cy

[0054] In some embodiments, Cy 1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0055] is 1

Chemical formula

Chemical formula

Chem.

Chem.

Chem.

[0056] is 1 is

Chem.

Chem.

Chem.

Chem.

[0057] In some embodiments, Cy 1 is [Chemical formula] is as follows, where R 1 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 1 is [Chemical formula] is as follows, where R 1 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 1 is [Chemical formula] is as follows, where R 1 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 1 is [Chemical formula] is as follows, where R 1 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 1 is [Chemical formula] is as follows, where R 1 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 1 is [Chemical formula] and in the formula, R 1 is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, Cy 1 is

Chemical formula

[0058] In some embodiments, Cy 1 is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 1 is substituted with n R 1 and in the formula, R 1 is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, Cy 1 is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 1 is substituted with n R 1 and in the formula, R 1 is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, Cy 1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0059] In some embodiments, Cy 1 is selected from the groups shown in the compounds of Table 1. In some embodiments, Cy 1 is

Chemical formula

[0060] As defined generally above, Cy 2 is phenyl; naphthyl; cubanyl; adamantyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 2 is substituted with m R 2 .

[0061] In some embodiments, Cy 2 is phenyl, where Cy 2 is substituted with m R 2 . In some embodiments, Cy 2 is naphthyl, where Cy 2 is substituted with m R 2 . In some embodiments, Cy 2 is cubanyl, where Cy 2 is substituted with m R 2 . In some embodiments, Cy 2 is adamantyl, where Cy 2is replaced by m Rs 2 In some embodiments, Cy 2 is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 2 is replaced by m Rs 2 In some embodiments, Cy 2 is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 2 is replaced by m Rs 2 In some embodiments, Cy 2 is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, where Cy 2 is replaced by m Rs 2 In some embodiments, Cy 2 is a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, where Cy 2 is replaced by m Rs 2 In some embodiments, Cy 2 is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 2 is replaced by m Rs 2 In some embodiments, Cy 2 is a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 2 is replaced by m Rs 2 In some embodiments, Cy

[0062] In some embodiments, Cy 2 is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 2 is replaced by m Rs 2 In some embodiments, Cy 2is a 9- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 2 is substituted with m R 2 . In some embodiments, Cy 2 is an 8- to 9-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 2 is substituted with m R 2 . In some embodiments, Cy 2 is an 8-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 2 is substituted with m R 2 . In some embodiments, Cy 2 is a 9-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 2 is substituted with m R 2 . In some embodiments, Cy 2 is a 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 2 is substituted with m R 2 .

[0063] In some embodiments, Cy 2 is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, where Cy 2 is substituted with m R 2 . In some embodiments, Cy 2 is a 4- to 6-membered saturated or partially unsaturated monocyclic carbocyclic ring, where Cy 2 is substituted with m R 2 . In some embodiments, Cy 2 is a 4- to 5-membered saturated or partially unsaturated monocyclic carbocyclic ring, where Cy 2 is substituted with m R 2 . In some embodiments, Cy 2is a 5- to 6-membered saturated or partially unsaturated monocyclic carbocyclic ring, where Cy 2 is substituted with m R 2 . In some embodiments, Cy 2 is a 4-membered saturated or partially unsaturated monocyclic carbocyclic ring, where Cy 2 is substituted with m R 2 . In some embodiments, Cy 2 is a 5-membered saturated or partially unsaturated monocyclic carbocyclic ring, where Cy 2 is substituted with m R 2 . In some embodiments, Cy 2 is a 6-membered saturated or partially unsaturated monocyclic carbocyclic ring, where Cy 2 is substituted with m R 2 .

[0064] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0065] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0066] In some embodiments, Cy 2 is a 7- to 12-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Cy 2 is substituted with m R 2 . In some embodiments, Cy 2 is an 8- to 10-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Cy 2 is substituted with m R 2 . In some embodiments, Cy 2 is an 8- to 9-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Cy 2 is substituted with m R 2 . In some embodiments, Cy 2 is an 8-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Cy 2 is substituted with m R 2 . In some embodiments, Cy 2is a 9-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 2 is substituted with m R 2 .

[0067] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0068] In some embodiments, Cy 2 is

Chemical formula

[0069] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0070] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0071] In some embodiments, Cy 2 is [Chemical formula] and, in some embodiments, Cy 2 is [Chemical formula] and, in some embodiments, Cy 2 is [Chemical formula] and, in some embodiments, Cy 2 is [Chemical formula] and, in some embodiments, Cy 2 is [Chemical formula] and, in some embodiments, Cy

[0072] is 2 is [Chemical formula] and, in the formula, R 2is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0073] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0074] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0075] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0076] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chem.

Chem.

Chem.

[0077] In some embodiments, Cy 2 is

Chem.

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[0078] In some embodiments, Cy 2 is

Chem.

Chem.

Chem.

Chem.

Chem.

[0079] In some embodiments, Cy 2 is

Chem.

[0080] In some embodiments, Cy 2 is [Chemical formula] is, wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemical formula] is, wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemical formula] is, wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemical formula] is, wherein R 2is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, Cy 2 is

Chemical formula

[0081] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0082] is 2 is

Chemical formula

[0083] In some embodiments, Cy 2 is [Chemical formula] which is. In some embodiments, Cy 2 is [Chemical formula] which is. In some embodiments, Cy 2 is [Chemical formula] which is. In some embodiments, Cy 2 is [Chemical formula] is. In some embodiments, Cy 2 is [Chemical formula] is.

[0084] In some embodiments, Cy 2 is [Chemical formula] wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemical formula] wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemical formula] wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemical formula] wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemical formula] wherein R 2 is as defined in the embodiments, classes, and subclasses herein.

[0085] In some embodiments, Cy 2 is

Chem.

Chem.

Chem.

Chem.

Chem.

[0086] In some embodiments, Cy 2 is

Chem.

Chem.

Chem.

[0087] In some embodiments, Cy 2 is [Chemical formula] In some embodiments, Cy 2 is [Chemical formula] In some embodiments, Cy 2 is [Chemical formula] In some embodiments, Cy 2 is [Chemical formula] In some embodiments, Cy 2 is [Chemical formula] In some embodiments, Cy

[0088] In some embodiments, Cy 2 is

Chem.

Chem.

Chem.

Chem.

Chem.

[0089] In some embodiments, Cy 2 is

Chem.

Chem.

Chem.

Chem.

Chem.

[0090] In some embodiments, Cy 2 is

Chem.

Chem.

Chem.

Chem.

Chem.

[0091] In some embodiments, Cy 2 is

Chem.

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0092] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

[0093] In some embodiments, Cy 2 is [Chemistry] It is, wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemistry] It is, wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemistry] It is, wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemistry] It is, wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemistry] and, in the formula, R 2 is as defined in the embodiments, classes, and subclasses of this specification.

[0094] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0095] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

[0096] In some embodiments, Cy 2 is [Chemical formula] In some embodiments, Cy 2 is [Chemical formula] In some embodiments, Cy 2 is [Chemical formula] In some embodiments, Cy 2 is [Chemical formula] In some embodiments, Cy 2 is [Chemical formula] is as follows.

[0097] In some embodiments, Cy 2 is [Chemical formula] wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemical formula] wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemical formula] wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemical formula] wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemical formula] wherein R 2 is as defined in the classes and subclasses herein.

[0098] In some embodiments, Cy 2 is [Chemical formula] It is. In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0099] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

[0100] In some embodiments, Cy 2 is [Chemical formula] which is. In some embodiments, Cy 2 is [Chemical formula] which is. In some embodiments, Cy 2 is [Chemical formula] which is. In some embodiments, Cy 2 is [Chemical formula] which is. In some embodiments, Cy 2 is [Chemical formula] which is.

[0101] In some embodiments, Cy 2 is [Chemical formula] which is, wherein, R 2is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, Cy 2 is [Chemical formula] wherein R 2 is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, Cy 2 is [Chemical formula] wherein R 2 is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, Cy 2 is [Chemical formula] wherein R 2 is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, Cy 2 is [Chemical formula] wherein R 2 is as defined in the embodiments, classes, and subclasses of this specification.

[0102] In some embodiments, Cy 2 is [Chemical formula] In some embodiments, Cy 2 is [Chemical formula] In some embodiments, Cy 2 is [Chemical formula] is. In some embodiments, Cy 2 is

Chemical formula

Chemical formula

[0103] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0104] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0105] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

[0106] In some embodiments, Cy 2 is [Chemical formula] wherein in some embodiments, Cy 2 is [Chemical formula] wherein in some embodiments, Cy 2 is [Chemical formula] wherein in some embodiments, Cy 2 is [Chemical formula] wherein in some embodiments, Cy 2 is [Chemical formula] wherein in some embodiments, Cy

[0107] In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0108] In some embodiments, Cy 2 is

Chemical formula

[0109] In some embodiments, Cy 2 is [Chemistry] is, wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemistry] is, wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemistry] is, wherein R 2 is as defined in the embodiments, classes, and subclasses herein. In some embodiments, Cy 2 is [Chemistry] is, wherein R 2is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, Cy 2 is

Chemical formula

[0110] In some embodiments, Cy 2 is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 2 is substituted with m R 2 s. In some embodiments, Cy 2 is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 2 is substituted with m R 2 s. In some embodiments, Cy 2 is pyridyl, pyrimidinyl, pyridazinyl, triazinyl, or tetrazinyl. In some embodiments, Cy 2 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0111] In some embodiments, Cy 2 is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where Cy 2 is substituted with m R 2 In some embodiments, Cy 2 is aziridinyl, oxiranyl, azetidinyl, oxetanyl, pyrrolidinyl, piperidinyl, piperazinyl, tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, morpholinyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, thiomorpholinyl, azepanyl, homomorpholinyl, and homothiomorpholinyl. In some embodiments, Cy 2 is azetidinyl, pyrrolidinyl, or piperidinyl. In some embodiments, Cy 2 is

Chemical formula

[0112] In some embodiments, Cy 2 is selected from the groups shown in the compounds of Table 1.

[0113] As defined generally above, Q is L Q wherein L Q is as defined in the embodiments, classes, and subclasses of this specification.

[0114] In some embodiments, Q is a covalent bond, or a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-4 where one or two methylene units of the chain are optionally and independently replaced by -CH(R L )-, -C(R L )2-, C 3-6 cycloalkylene, C 3-6 heterocycloalkylene, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-. In some embodiments, Q is a covalent bond. In some embodiments, Q is a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-4 where one or two methylene units of the chain are optionally and independently replaced by -CH(R L )-, -C(R L )2-, C 3-6 cycloalkylene, C 3-6 heterocycloalkylene, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-. In some embodiments, Q is a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-4 .

[0115] In some embodiments, Q is a divalent saturated or unsaturated hydrocarbon chain of C 1-2 where one or two methylene units of the chain are optionally and independently replaced by -CH(R L )-, -C(R L )2-, C 3-6 cycloalkylene, C 3-6is replaced by a heterocycloalkylene, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-. In some embodiments, Q is C 1-2 is a divalent saturated or unsaturated hydrocarbon chain of C, where one or two methylene units of the chain are optionally and independently -CH(R L )-, -C(R L )2-, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, or -O-. In some embodiments, Q is C 1-2 is a divalent saturated or unsaturated hydrocarbon chain of C.

[0116] In some embodiments, Q is -C(O)N(R)-, -C(O)N(R)CH2-, -N(R)-, -CH2C(O)N(R)-, -N(R)C(O)N(R)-, or a covalent bond. In some embodiments, Q is -C(O)N(H)-, -C(O)N(H)CH2-, -N(H)-, -CH2C(O)N(H)-, -N(H)C(O)N(H)-, or a covalent bond. In some embodiments, Q is -C(O)N(H)-, -C(O)N(H)CH2-, or a covalent bond. In some embodiments, Q is -C(O)N(H)- or -C(O)N(H)CH2-. In some embodiments, Q is -C(O)N(H)-. In some embodiments, Q is -C(O)N(H)CH2-. In some embodiments, Q is -N(H)-. In some embodiments, Q is -CH2C(O)N(H)-. In some embodiments, Q is -N(H)C(O)N(H)-. In some embodiments, Q is a covalent bond.

[0117] In some embodiments, Q is selected from the groups shown in the compounds of Table 1.

[0118] As defined generally above, T is a divalent C T aliphatic chain substituted with q R 1-3 s. In some embodiments, T is a divalent C T aliphatic chain substituted with q R 2-3 s. In some embodiments, T is a divalent C T aliphatic chain substituted with q R 1-2 s. In some embodiments, T is a divalent C1 aliphatic chain substituted with q R T s. In some embodiments, T is a divalent C2 aliphatic chain substituted with q R T s. In some embodiments, T is a divalent C3 aliphatic chain substituted with q R T s.

[0119] In some embodiments, T is

Chemical formula

Chemical formula

Chemical formula

[0120] In some embodiments, T is

Chemical formula

Chemical formula

Chemical formula

[0121] In some embodiments, T is

Chemical formula

Chemical formula

Chemical formula

[0122] In some embodiments, T is

Chemical formula

Chemical formula

Chemical formula

[0123] In some embodiments, T is

Chemical formula

Chemical formula

[0124] In some embodiments, T is [Chemical formula] wherein [Chemical formula] represents a bond to Q, [Chemical formula] represents a bond to Cy 1 and R T is as defined in the embodiments, classes, and subclasses of this specification.

[0125] In some embodiments, T is [Chemical formula] wherein [Chemical formula] represents a bond to Q, [Chemical formula] represents a bond to Cy 1 and R T is as defined in the embodiments, classes, and subclasses of this specification.

[0126] In some embodiments, T is [Chemical formula] wherein [Chem.] represents a bond to Q, [Chem.] is a bond to Cy, and R 1 is as defined in the embodiments, classes, and subclasses of this specification. T

[0127] In some embodiments, T is [Chem.] wherein [Chem.] represents a bond to Q, [Chem.] is a bond to Cy, and R 1 is as defined in the embodiments, classes, and subclasses of this specification. T

[0128] In some embodiments, T is [Chem.] wherein [Chem.] represents a bond to Q, [Chem.] is a bond to Cy, and R 1 is as defined in the embodiments, classes, and subclasses of this specification. T

[0129] In some embodiments, T is [Chemistry] wherein [Chemistry] represents a bond to Q, [Chemistry] is a bond to Cy 1 , and R T is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, T is [Chemistry] wherein [Chemistry] represents a bond to Q, [Chemistry] is a bond to Cy 1 , and R T is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, T is [Chemistry] wherein [Chemistry] represents a bond to Q, [Chemistry] is a bond to Cy 1 , and R T is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, T is [Chemistry] wherein

Chem.

Chem.

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[0130] In some embodiments, T is

Chemical formula

Chemical formula

Chemical formula

[0131] In some embodiments, T is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

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[0132] In some embodiments, T is

Chemical formula

Chemical formula

Chemical formula

[0133] In some embodiments, T is

Chemical formula

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Chemical formula

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[0134] In some embodiments, T is

Chemical formula

Chemical formula

Chemical formula

[0135] In some embodiments, T is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0136] In some embodiments, T is [Chem.] wherein [Chem.] represents the bond to Q, [Chem.] is the bond to Cy 1 and R TTC and p 1 are as defined in the embodiments, classes, and subclasses of this specification.

[0137] In some embodiments, T is [Chem.] wherein [Chem.] represents the bond to Q, [Chem.] is the bond to Cy 1 and R TTC and p 1 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, T is [Chem.] wherein, [Chemical formula] represents a bond to Q, [Chemical formula] is a bond to Cy 1 and R TTC and p 1 are as defined in the embodiments, classes, and subclasses herein. In some embodiments, T is [Chemical formula] wherein, [Chemical formula] represents a bond to Q, [Chemical formula] is a bond to Cy 1 and R TTC and p 1 are as defined in the embodiments, classes, and subclasses herein. In some embodiments, T is [Chemical formula] wherein, [Chemical formula] represents a bond to Q, [Chemical formula] is a bond to Cy 1 and R TTC and p 1 are as defined in the embodiments, classes, and subclasses herein. In some embodiments, T is [Chemical formula] and in the formula, each R TC is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, T is

Chemical formula

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Chemical formula

Chemical formula

Chemical formula

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Chemical formula

[0138] In some embodiments, T is selected from the groups shown in the compounds of Table 1.

[0139] As defined generally above, each R 1 is, independently, -L 1 -R 1A or two of R 1 together with their intervening atoms form a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is substituted with p 2 number of R 11C or one of R T and one of R 1 together with their intervening atoms form a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is substituted with p 4 number of R T1C is substituted.

[0140] In some embodiments, each R 1 is, independently, -L 1 -R 1A In some embodiments, each R 1 is, independently, -R 1A is.

[0141] In some embodiments, each R 1 is, independently, R AIt is. In some embodiments, each R 1 (i.e., -L 1 -R 1A (collectively) is independently oxo, deuterium, halogen, -CN, -NO2, -OR, -SF5, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -S(O)(NCN)R, -S(NCN)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2, wherein R is as defined in the embodiments, classes, and subclasses herein.)

[0142] In some embodiments, R 1 is oxo. In some embodiments, R 1 is deuterium. In some embodiments, each R 1 is independently halogen. In some embodiments, R 1 is -CN. In some embodiments, R 1 is -NO2. In some embodiments, each R 1 is independently -OR, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, R 1 is -SF5. In some embodiments, each R 1 is independently SR, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is independently -NR2, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1is, independently, -S(O)2R, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -S(O)2NR2, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, R 1 is -S(O)2F. In some embodiments, each R 1 is, independently, -S(O)R, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -S(O)NR2, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -S(O)(NR)R, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -S(O)(NCN)R, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -S(NCN)R, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -C(O)R, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -C(O)OR, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -C(O)NR2, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1is, independently, -C(O)N(R)OR, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -OC(O)R, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -OC(O)NR2, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -N(R)C(O)OR, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -N(R)C(O)R, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -N(R)C(O)NR2, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -N(R)C(NR)NR2, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -N(R)S(O)2NR2, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -N(R)S(O)2R, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -P(O)R2, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1is, independently, -P(O)(R)OR, wherein R is as defined in the embodiments, classes, and subclasses herein. In some embodiments, each R 1 is, independently, -B(OR)2, wherein R is as defined in the embodiments, classes, and subclasses herein.

[0143] In some embodiments, each R 1 is, independently, r 1 R's 1C substituted by B R. In some embodiments, R 1 (i.e., the general term of -L 1 -R 1A ) is a C 1-6 aliphatic chain; phenyl; naphthyl; cubanyl; adamantyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 1 R's 1C .

[0144] In some embodiments, each R 1 (i.e., the general term of -L 1 -R 1A ) is independently a halogen, -CN, -OR, or a C 1 aliphatic chain substituted by r 1-6 halogens. In some embodiments, each R 1 is independently a halogen, -CN, -OR, or a C 1-6It is an aliphatic chain. In some embodiments, each R 1 is, independently, halogen, -CN, -O-(a C 1-6 aliphatic chain substituted with 0 to 5 halogens), or a C 1-6 aliphatic chain substituted with 0 to 5 halogens. In some embodiments, each R 1 is, independently, halogen or a C 1-6 aliphatic chain substituted with 0 to 5 halogens. In some embodiments, each R 1 is, independently, halogen or a C 1-6 aliphatic chain substituted with 0 to 4 halogens. In some embodiments, each R 1 is, independently, halogen or a C 1-6 aliphatic chain substituted with 0 to 3 halogens. In some embodiments, each R 1 is, independently, halogen or a C 1-3 aliphatic chain substituted with 0 to 3 halogens. In some embodiments, each R 1 is, independently, halogen or a C 1-3 aliphatic chain substituted with 0 to 2 halogens.

[0145] In some embodiments, each R 1 is, independently, a halogen selected from Br, Cl, and F. In some embodiments, each R 1 is, independently, a halogen selected from Cl and F. In some embodiments, R 1 is Cl. In some embodiments, R 1 is F.

[0146] In some embodiments, at least one R 1 is halogen. In some embodiments, at least two R 1 are halogen. In some embodiments, at least three R 1 are halogen. In some embodiments, one of R 1 is Cl. In some embodiments, R 1Two of them are Cl. In some embodiments, R 1 One of them is F. In some embodiments, R 1 Two of them are F. In some embodiments, R 1 One of them is Cl, and R 1 One of them is F. In some embodiments, R 1 Two of them are Cl, and R 1 One of them is F. In some embodiments, R 1 One of them is Cl, and R 1 Two of them are F.

[0147] In some embodiments, each R 1 is independently an aliphatic chain substituted with 0 to 5 halogens on a C 1-6 In some embodiments, each R 1 is independently an aliphatic chain substituted with 0 to 4 halogens on a C 1-6 In some embodiments, each R 1 is independently an aliphatic chain substituted with 0 to 3 halogens on a C 1-6 In some embodiments, each R 1 is independently an aliphatic chain substituted with 0 to 3 halogens on a C 1-3 In some embodiments, each R 1 is independently an aliphatic chain substituted with 0 to 2 halogens on a C 1-3 In some embodiments, each R

[0148] In some embodiments, at least one R 1 is an aliphatic optionally substituted with 1 to 3 halogens on a C 1-3 In some embodiments, at least one R 1 is an -O-C 1-3 aliphatic optionally substituted with 1 to 3 halogens.

[0149] In some embodiments, each R 1 (i.e., -L 1 -R 1A(collectively) are independently halogen, -OH, -OCH3, or C optionally substituted with 1 to 3 halogens 1-3 is aliphatic. In some embodiments, each R 1 is independently fluorine, chlorine, -OCH3, or -CH3. In some embodiments, R 1 is -OH. In some embodiments, R 1 is -CH3. In some embodiments, R 1 is -OCH3. In some embodiments, R 1 is -CF3. In some embodiments, R 1 is -CHF2.

[0150] In some embodiments, two of the Rs 1 together with their intervening atoms form a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is substituted with p 2 number of Rs 11C and p 2 and R 11C are as defined in the embodiments, classes, and subclasses herein.

[0151] In some embodiments, one of the Rs T and one of the Rs 1 together with their intervening atoms form a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is substituted with p 4 number of Rs T1C and p 4 and R T1C are as defined in the embodiments, classes, and subclasses herein.

[0152] In some embodiments, R 1 is selected from the groups shown in the compounds of Table 1.

[0153] As defined generally above, each R 2 is, independently, -L 2 -R 2A or two of the Rs 2 , together with their intervening atoms, form a 3- to 7-membered saturated, partially unsaturated or aromatic carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is substituted with p 3 number of Rs 22C .

[0154] In some embodiments, each R 2 is, independently, -L 2 -R 2A . In some embodiments, each R 2 is, independently, R 2A .

[0155] In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is -N(R)-R 2A , where R and R 2A are as defined in the embodiments, classes, and subclasses herein. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is -NH-R 2A , where R 2A is as defined in the embodiments, classes, and subclasses herein. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is -CH(R L )-R 2A , where R and R 2A are as defined in the embodiments, classes, and subclasses herein. In some embodiments, R 2 (i.e., the general term for -L 2 -R2A (collectively) is -CH2-R 2A where R 2A is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., -L 2 -R 2A (collectively) is -N(R)C(O)-R 2A where R and R 2A are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., -L 2 -R 2A (collectively) is -NHC(O)-R 2A where R 2A is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., -L 2 -R 2A (collectively) is -N(R)C(O)CH(R L )-R 2A where R and R 2A are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., -L 2 -R 2A (collectively) is -NHC(O)CH2-R 2A where R 2A is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., -L 2 -R 2A (collectively) is -N(R)C(O)N(R)-R 2A where R and R 2A are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., -L 2 -R 2A (collectively) is -NHC(O)NH-R 2A where R 2Ais as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term of -L 2 -R 2A ) is -N(R)C(O)CH(R L )O-R 2A , where R and R 2A are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term of -L 2 -R 2A ) is -NHC(O)CH2O-R 2A , where R 2A is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term of -L 2 -R 2A ) is -CH(R L )N(R)-R 2A , where R and R 2A are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term of -L 2 -R 2A ) is -CH(R L )O-R 2A , where R and R 2A are as defined in the embodiments, classes, and subclasses of this specification.

[0156] In some embodiments, R 2 is -N(R)-R 2A , -N(R)C(O)-R 2A , -CH(R L )N(R)-R 2A , -N(R)C(O)CH(R L )-R 2A , -CH(R L )O-R 2A , -CH(R L )-R 2A , or -R 2AIt is. In some embodiments, R 2 is -N(R)-R 2A , -N(R)C(O)-R 2A , -CH(R L )N(R)-R 2A , or -R 2A is. In some embodiments, R 2 is -N(R)-R 2A , -N(R)C(O)-R 2A , or -R 2A is. In some embodiments, R 2 is -N(R)C(O)-R 2A or -R 2A is.

[0157] In some embodiments, R 2 is -N(H)-R 2A , -N(H)C(O)-R 2A , -CH2N(H)-R 2A , -N(H)C(O)CH2-R 2A , -CH2O-R 2A , -CH2-R 2A , or -R 2A is. In some embodiments, R 2 is -N(H)-R 2A , -N(H)C(O)-R 2A , -CH2N(H)-R 2A , or -R 2A is. In some embodiments, R 2 is -N(H)-R 2A , -N(H)C(O)-R 2A , or -R 2A is. In some embodiments, R 2 is -N(H)C(O)-R 2A or -R 2A is.

[0158] In some embodiments, R 2 (i.e., the general term of -L 2 -R 2A ) is

Chemical Formula

[0159] In some embodiments, R 2 (that is, the general term of -L 2 -R 2A ) is

Chemical formula

[0160] In some embodiments, R 2 (that is, the general term of -L 2 -R 2A ) is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0161] In some embodiments, R 2 (that is, a general term for -L 2 -R 2A ) is [Chemical formula] and in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (that is, a general term for -L 2 -R 2A ) is [Chemical formula] and in the formula, R 2Cand r 2 is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., -L 2 -R 2A in general) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., -L 2 -R 2A in general) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification.

[0162] In some embodiments, R 2 (i.e., -L 2 -R 2A in general) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., -L 2 -R 2A in general) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., -L 2 -R2A collectively) is, [Chem.] and in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., -L 2 -R 2A collectively) is, [Chem.] and in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., -L 2 -R 2A collectively) is, [Chem.] and in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification.

[0163] In some embodiments, R 2 (i.e., -L 2 -R 2A collectively) is, [Chem.] and in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification.

[0164] In some embodiments, R 2 (i.e., -L 2 -R 2A collectively) is, [Chem.] is as follows.

[0165] In some embodiments, R 2 (i.e., the general term of -L 2 -R 2A ) is [Chemical formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification.

[0166] In some embodiments, R 2 (i.e., the general term of -L 2 -R 2A ) is [Chemical formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term of -L 2 -R 2A ) is [Chemical formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term of -L 2 -R 2A ) is [Chemical formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term of -L 2 -R2A (a generic term for) is [Chem.] and in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the generic term for -L 2 -R 2A ) is [Chem.] and in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the generic term for -L 2 -R 2A ) is [Chem.] and in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the generic term for -L 2 -R 2A ) is [Chem.] and in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the generic term for -L 2 -R 2A ) is [Chem.] and in the formula, R 2C and r 2is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] , where R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] , where R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] , where R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] , where R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] and in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (that is, the general term of -L 2 -R 2A ) is [Chemical Formula] and in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (that is, the general term of -L 2 -R 2A ) is [Chemical Formula] and in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (that is, the general term of -L 2 -R 2A ) is [Chemical Formula] and in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification.

[0167] In some embodiments, R 2 (that is, the general term of -L 2 -R 2A ) is [Chemical Formula] and in the formula, R 2C and r 2is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification.

[0168] In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification.

[0169] In some embodiments, R 2 (i.e., -L 2 -R 2A (collectively)) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification.

[0170] In some embodiments, R 2 (i.e., -L 2 -R 2A (collectively)) is [Chemical Formula] wherein R 2C is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., -L 2 -R 2A (collectively)) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., -L 2 -R 2A (collectively)) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., -L 2 -R 2A (collectively)) is [Chemical formula] and, in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical formula] and, in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical formula] and, in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical formula] and, in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification.

[0171] In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical formula] and, in the formula, R 2A , R 2C , and r 2is as defined in the embodiments, classes, and subclasses of this specification.

[0172] In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term of -L 2 -R 2A ) is [Chemical formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term of -L 2 -R 2A ) is [Chemical formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term of -L 2 -R 2A ) is [Chemical formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term of -L 2 -R 2A ) is [Chemical formula] wherein R 2C and r 2is as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] wherein R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification. In some embodiments, R 2 (i.e., the general term for -L 2 -R 2A ) is [Chemical Formula] and in the formula, R 2C and r 2 are as defined in the embodiments, classes, and subclasses of this specification.

[0173] In some embodiments, each R 2 (i.e., the general term of -L 2 -R 2A ) is independently halogen, -OH, -OCH3, or C optionally substituted with 1 to 3 halogens 1-3 which is aliphatic. In some embodiments, each R 2 is independently fluorine, chlorine, -OCH3, or -CH3. In some embodiments, R 2 is -OH. In some embodiments, R 2 is -CH3. In some embodiments, R 2 is -OCH3. In some embodiments, R 2 is -CF3. In some embodiments, R 2 is -CHF2.

[0174] In some embodiments, two of the Rs 2 , together with their intervening atoms, form a 3- to 7-membered saturated, partially unsaturated or aromatic carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is p 3 substituted with 22C Rs. In some embodiments, two of the Rs 2 , together with their intervening atoms, form a 3- to 7-membered saturated, partially unsaturated or aromatic carbocyclic ring, where the ring is p 3 substituted with 22C Rs. In some embodiments, two of the Rs 2 , together with their intervening atoms, form a 6-membered aromatic carbocyclic ring, where the ring is p 3 substituted with 22C Rs.

[0175] In some embodiments, R 2 is selected from the groups shown in the compounds of Table 1.

[0176] As defined generally above, each R T is independently -L T -R TA or two of the Rs, together with their intervening atoms, form a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is substituted with p T number of Rs 1 or one of the Rs and one of the Rs, together with their intervening atoms, form a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is substituted with p TTC number of Rs T or one of the Rs and one of the Rs, together with their intervening atoms, form a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is substituted with p 1 number of Rs 4 number of Rs T1C or one of the Rs and one of the Rs, together with their intervening atoms, form a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is substituted with p T number of Rs L number of Rs 5 number of Rs TLC number of Rs.

[0177] In some embodiments, each R T is independently -L T -R TA In some embodiments, each R T is independently -R TA In some embodiments, each R T is independently R A In some embodiments, each R T is independently r 3Individual R TC R substituted by B is.

[0178] In some embodiments, R T (i.e., -L T -R TA in general) is C 1-6 aliphatic chain; phenyl; naphthyl; cubanyl; adamantyl; 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is r 3 individual R TC substituted.

[0179] In some embodiments, R T is C 1-6 aliphatic chain; adamantyl; 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is r 3 individual R TC substituted.

[0180] In some embodiments, R T is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is r 3 individual R TCis replaced. In some embodiments, R T is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted with r 3 number of R TC .

[0181] In some embodiments, R T is a 3- to 7-membered saturated monocyclic carbocycle; a 5- to 12-membered saturated bicyclic carbocycle; a 3- to 7-membered saturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted with r 3 number of R TC . In some embodiments, R T is a 3- to 7-membered saturated monocyclic carbocycle; or a 5- to 12-membered saturated bicyclic carbocycle, each of which is substituted with r 3 number of R TC . In some embodiments, R T is a 3- to 7-membered saturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted with r 3 number of R TC .

[0182] In some embodiments, R T (i.e., the general term of -L T -R TA ) is a C 1-6 aliphatic chain substituted with r 3 number of R TC . In some embodiments, R T (i.e., the general term of -L T -R TA ) is r 3is phenyl substituted with R TC . In some embodiments, R T (i.e., the general term for -L T -R TA ) is naphthyl substituted with r 3 R TC . In some embodiments, R T (i.e., the general term for -L T -R TA ) is cubanyl substituted with r 3 R TC . In some embodiments, R T (i.e., the general term for -L T -R TA ) is adamantyl substituted with r 3 R TC . In some embodiments, R T (i.e., the general term for -L T -R TA ) is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is substituted with r 3 R TC . In some embodiments, R T (i.e., the general term for -L T -R TA ) is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is substituted with r 3 R TC . In some embodiments, R T (i.e., the general term for -L T -R TA ) is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, where the ring is substituted with r 3 R TC . In some embodiments, R T (i.e., the general term for -L T -R TA ) is a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, where the ring is substituted with r 3 R TCis replaced. In some embodiments, R T (i.e., -L T -R TA in general) is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is substituted with r 3 number of R TC s. In some embodiments, R T (i.e., -L T -R TA in general) is a 7- to 12-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is substituted with r 3 number of R TC s.

[0183] In some embodiments, R T is

Chemical formula

[0184] In some embodiments, R T is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0185] In some embodiments, two of R T , together with their intervening atoms, form a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is substituted with p 1 R TTC .

[0186] In some embodiments, one of R T and R 1One of them, together with those intervening atoms, forms a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is substituted with p 4 R T1C substituents.

[0187] In some embodiments, one of R T and one of R L together with those intervening atoms, form a 3- to 7-membered saturated or partially unsaturated carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is substituted with p 5 R TLC substituents.

[0188] In some embodiments, R T is selected from the groups shown in the compounds of Table 1.

[0189] As defined generally above, L 1 is a covalent bond or a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-4 , wherein one or two methylene units of the chain are optionally and independently replaced by -CH(R L )-, -C(R L )2-, C 3-6 cycloalkylene, C 3-6 heterocycloalkylene, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-. In some embodiments, L 1 is a covalent bond. In some embodiments, L 1 is a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-4 , wherein one or two methylene units of the chain are optionally and independently -CH(RL )-, -C(R L )2-, C 3-6 cycloalkylene, C 3-6 heterocycloalkylene, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-. In some embodiments, L 1 is a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-4 .

[0190] In some embodiments, L 1 is a divalent saturated or unsaturated hydrocarbon chain of C 1-2 , wherein one or two methylene units of the chain are optionally and independently replaced by -CH(R L )-, -C(R L )2-, C 3-6 cycloalkylene, C 3-6 heterocycloalkylene, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-. In some embodiments, L 1 is a divalent saturated or unsaturated hydrocarbon chain of C 1-2 , wherein one or two methylene units of the chain are optionally and independently replaced by -CH(R L )-, -C(R L )2-, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, or -O-. In some embodiments, L 1 is a divalent saturated or unsaturated hydrocarbon chain of C 1-2 .

[0191] In some embodiments, L 1 is selected from the groups shown in the compounds of Table 1.

[0192] As defined generally above, L 2 is a covalent bond, or a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-4 , where one or two methylene units of the chain are optionally and independently replaced by -CH(R L ), -C(R L )2-, C 3-6 cycloalkylene, C 3-6 heterocycloalkylene, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-. In some embodiments, L 2 is a covalent bond. In some embodiments, L 2 is a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-4 , where one or two methylene units of the chain are optionally and independently replaced by -CH(R L ), -C(R L )2-, C 3-6 cycloalkylene, C 3-6 heterocycloalkylene, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-. In some embodiments, L 2 is a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-4 .

[0193] In some embodiments, L 2 is a divalent saturated or unsaturated hydrocarbon chain of C 1-2 , where one or two methylene units of the chain are optionally and independently replaced by -CH(R L ), -C(R L )2-, C 3-6 cycloalkylene, C 3-6It is replaced by a heterocycloalkylene, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-. In some embodiments, L 2 is a divalent saturated or unsaturated hydrocarbon chain of C 1-2 , wherein one or two methylene units of the chain are optionally and independently replaced by -CH(R L ), -C(R L )2-, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, or -O-. In some embodiments, L 2 is a divalent saturated or unsaturated hydrocarbon chain of C 1-2 .

[0194] In some embodiments, L 2 is -N(R)-, -N(R)C(O)-, -CH(R L )N(R)-, -N(R)C(O)CH(R L )-, -CH(R L )O-, -CH(R L )-, or a covalent bond. In some embodiments, R 2 is -N(R)-, -N(R)C(O)-, -CH(R L )N(R)-, or a covalent bond. In some embodiments, R 2 is -N(R)-, -N(R)C(O)-, or a covalent bond. In some embodiments, R 2 is -N(R)C(O)- or a covalent bond.

[0195] In some embodiments, R 2 is -N(H)-, -N(H)C(O)-, -CH2N(H)-, -N(H)C(O)CH2-, -CH2O-, -CH2-, or a covalent bond. In some embodiments, R 2is -N(H)-, -N(H)C(O)-, -CH2N(H)-, or a covalent bond. In some embodiments, R 2 is -N(H)-, -N(H)C(O)-, or a covalent bond. In some embodiments, R 2 is -N(H)C(O)- or a covalent bond.

[0196] In some embodiments, L 2 is -N(R)C(O)- or -N(R)C(O)N(R)-. In some embodiments, L 2 is -N(H)C(O)- or -N(H)C(O)N(H)-. In some embodiments, L 2 is -N(R)C(O)-. In some embodiments, L 2 is -N(H)C(O)-. In some embodiments, L 2 is -N(R)C(O)N(R)-. In some embodiments, L 2 is -N(H)C(O)N(H)-. In some embodiments, L 2 is -N(R)-. In some embodiments, L 2 is -N(H)-. In some embodiments, L 2 is a covalent bond. In some embodiments, L 2 is -CH(R L )N(R)-. In some embodiments, L 2 is -N(R)C(O)CH(R L )-. In some embodiments, L 2 is -CH(R L )O-. In some embodiments, L 2 is -CH(R L )-.

[0197] In some embodiments, L 2 is selected from the groups shown in the compounds of Table 1.

[0198] As defined generally above, L Qis a covalent bond, or a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-4 where one or two methylene units of the chain are optionally and independently replaced by -CH(R L )-, -C(R L )2-, C 3-6 cycloalkylene, C 3-6 heterocycloalkylene, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-. In some embodiments, L Q is a covalent bond. In some embodiments, L Q is a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-4 where one or two methylene units of the chain are optionally and independently replaced by -CH(R L )-, -C(R L )2-, C 3-6 cycloalkylene, C 3-6 heterocycloalkylene, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-. In some embodiments, L Q is a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-4 .

[0199] In some embodiments, L Q is a divalent saturated or unsaturated hydrocarbon chain of C 1-2 where one or two methylene units of the chain are optionally and independently replaced by -CH(R L )-, -C(R L )2-, C 3-6 cycloalkylene, C 3-6It is replaced by a heterocycloalkylene, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-. In some embodiments, L Q is a divalent saturated or unsaturated hydrocarbon chain of C 1-2 , where one or two methylene units of the chain are optionally and independently replaced by -CH(R L )-, -C(R L )2-, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, or -O-. In some embodiments, L Q is a divalent saturated or unsaturated hydrocarbon chain of C 1-2 .

[0200] In some embodiments, L Q is -C(O)N(R)-, -C(O)N(R)CH2-, -N(R)-, -CH2C(O)N(R)-, -N(R)C(O)N(R)-, or a covalent bond. In some embodiments, L Q is -C(O)N(H)-, -C(O)N(H)CH2-, -N(H)-, -CH2C(O)N(H)-, -N(H)C(O)N(H)-, or a covalent bond. In some embodiments, L Q is -C(O)N(H)-, -C(O)N(H)CH2-, or a covalent bond. In some embodiments, L Q is -C(O)N(H)- or -C(O)N(H)CH2-. In some embodiments, L Q is -C(O)N(H)-. In some embodiments, L Q is -C(O)N(H)CH2-. In some embodiments, L Q is -N(H)-. In some embodiments, L Q is -CH2C(O)N(H)-. In some embodiments, L Qis -N(H)C(O)N(H)-. In some embodiments, L Q is a covalent bond.

[0201] In some embodiments, L Q Q is selected from the groups shown in the compounds of Table 1.

[0202] As defined generally above, L T is a covalent bond, or a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-4 , where one or two methylene units of the chain are optionally and independently replaced by -CH(R L )-, -C(R L )2-, C 3-6 cycloalkylene, C 3-6 heterocycloalkylene, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-. In some embodiments, L T is a covalent bond. In some embodiments, L T is a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-4 , where one or two methylene units of the chain are optionally and independently replaced by -CH(R L )-, -C(R L )2-, C 3-6 cycloalkylene, C 3-6 heterocycloalkylene, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-. In some embodiments, L X is a divalent saturated or unsaturated straight-chain or branched hydrocarbon chain of C 1-4 .

[0203] In some embodiments, LT is a divalent saturated or unsaturated hydrocarbon chain of C 1-2 , where one or two methylene units of the chain are optionally and independently replaced by -CH(R L ), -C(R L )2-, C 3-6 cycloalkylene, C 3-6 heterocycloalkylene, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-. In some embodiments, L T is a divalent saturated or unsaturated hydrocarbon chain of C 1-2 , where one or two methylene units of the chain are optionally and independently replaced by -CH(R L ), -C(R L )2-, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, or -O-. In some embodiments, L T is a divalent saturated or unsaturated hydrocarbon chain of C 1-2 .

[0204] In some embodiments, L T is selected from the groups shown in the compounds of Table 1.

[0205] As defined generally above, each R 1A is independently R 1 substituted by r 1C R or R A or R B . In some embodiments, each R 1A is independently R A . In some embodiments, each R 1A is independently R 1 substituted by r 1C R B .

[0206] In some embodiments, R 1A is phenyl; naphthyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where R 1A is substituted by r 1 number of R 1C .

[0207] In some embodiments, R 1A is phenyl substituted by r 1 number of R 1C . In some embodiments, R 1A is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where R 1A is substituted by r 1 number of R 1C . In some embodiments, R 1A is phenyl or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where R 1A is substituted by r 1 number of R 1C .

[0208] In some embodiments, R 1Ais phenyl; naphthyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, where R 1A is r 1 number of R 1C is substituted by.

[0209] In some embodiments, R 1A is oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, and phenyl substituted by r 1-6 number of groups independently selected from optionally substituted C 1 aliphatic. In some embodiments, R 1A is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where R 1A is oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, and optionally substituted C 1-6 number of groups independently selected from aliphatic 1is replaced by r groups. In some embodiments, R 1A is phenyl or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where R 1A is oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, and optionally substituted C 1-6 aliphatic, and is replaced by r groups independently selected therefrom. 1

[0210] In some embodiments, R 1A is phenyl substituted by 1 to 3 R 1C . In some embodiments, R 1A is phenyl substituted by 2 R 1C . In some embodiments, R 1A is phenyl substituted by 1 R 1C .

[0211] In some embodiments, R 1A is phenyl substituted by 1 to 3 groups independently selected from halogen, -CN, -O-(optionally substituted C 1-6 aliphatic), and optionally substituted C 1-6 aliphatic. In some embodiments, R 1A is phenyl substituted by halogen and 1 to 3 groups independently selected from halogen and optionally substituted C 1-3 aliphatic. In some embodiments, R 1A ​is phenyl substituted by 1 to 3 groups independently selected from fluorine, chlorine, -CH3, -CHF2, and -CF3.

[0212] In some embodiments, R 1A is phenyl substituted by 2 groups independently selected from halogen, -CN, -O-(optionally substituted C 1-6 aliphatic), and optionally substituted C 1-6 aliphatic. In some embodiments, R 1A is phenyl substituted by 2 groups independently selected from halogen and C 1-3 aliphatic optionally substituted by 1 to 3 halogens. In some embodiments, R 1A is phenyl substituted by 2 groups independently selected from fluorine, chlorine, -CH3, -CHF2, and -CF3.

[0213] In some embodiments, R 1A is phenyl substituted by 1 group selected from halogen, -CN, -O-(optionally substituted C 1-6 aliphatic), and optionally substituted C 1-6 aliphatic. In some embodiments, R 1A is phenyl substituted by 1 halogen or a C 1-3 aliphatic group optionally substituted by 1 to 3 halogens. In some embodiments, R 1A is phenyl substituted by 1 fluorine, chlorine, -CH3, -CHF2, or -CF3.

[0214] In some embodiments, each R 1Ais, independently, oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, or deuterium.

[0215] In some embodiments, each R 1A is, independently, oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0216] In some embodiments, R 1A is oxo. In some embodiments, each R 1A is, independently, halogen. In some embodiments, R 1A is -CN. In some embodiments, R 1A is -NO2. In some embodiments, each R 1A is, independently, -OR. In some embodiments, each R 1A is, independently, -SR. In some embodiments, each R 1A is, independently, -NR2. In some embodiments, each R 1A is, independently, -S(O)2R. In some embodiments, each R 1Ais, independently, -S(O)2NR2. In some embodiments, R 1A is -S(O)2F. In some embodiments, each R 1A is, independently, -S(O)R. In some embodiments, each R 1A is, independently, -S(O)NR2. In some embodiments, each R 1A is, independently, -S(O)(NR)R. In some embodiments, each R 1A is, independently, -C(O)R. In some embodiments, each R 1A is, independently, -C(O)OR. In some embodiments, each R 1A is, independently, -C(O)NR2. In some embodiments, each R 1A is, independently, -C(O)N(R)OR. In some embodiments, each R 1A is, independently, -OC(O)R. In some embodiments, each R 1A is, independently, -OC(O)NR2. In some embodiments, each R 1A is, independently, -N(R)C(O)OR. In some embodiments, each R 1A is, independently, -N(R)C(O)R. In some embodiments, each R 1A is, independently, -N(R)C(O)NR2. In some embodiments, each R 1A is, independently, -N(R)C(NR)NR2. In some embodiments, each R 1A is, independently, -N(R)S(O)2NR2. In some embodiments, each R 1A is, independently, -N(R)S(O)2R. In some embodiments, each R 1A is, independently, -P(O)R2. In some embodiments, each R 1A is, independently, -P(O)(R)OR. In some embodiments, each R 1A is, independently, -B(OR)2. In some embodiments, R 1A is deuterium.

[0217] In some embodiments, R 1A is halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0218] In some embodiments, R 1A is halogen, -CN, or -NO2. In some embodiments, R 1A is -OR, -SR, or -NR2. In some embodiments, R 1A is -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 1A is -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, R 1A is -OC(O)R or -OC(O)NR2. In some embodiments, R 1A is -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, or -N(R)S(O)2R. In some embodiments, R 1A is -P(O)R2 or -P(O)(R)OR.

[0219] In some embodiments, R 1A is -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R 1Ais -SR, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 1A is -NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, or -N(R)S(O)2R.

[0220] In some embodiments, R 1A is -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R 1A is -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 1A is -SR, -S(O)2R, or -S(O)R. In some embodiments, R 1A is -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 1A is -S(O)2NR2 or -S(O)NR2. In some embodiments, R 1A is -SR, -S(O)2R, -S(O)2NR2, or -S(O)R.

[0221] In some embodiments, R 1A is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R 1A is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R 1A is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R 1A is -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R 1A is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0222] In some embodiments, R 1A is -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R 1A is -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R 1A is -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0223] In some embodiments, R 1A is C 1-6 an aliphatic chain; phenyl; naphthyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is 1 substituted by r 1C number of R

[0224] In some embodiments, R 1A is 1 an aliphatic chain substituted by r 1C number of R 1-6 . In some embodiments, R 1A is 1 phenyl substituted by r 1C number of R 1A . In some embodiments, R 1 is 1C naphthyl substituted by r 1Ais a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is r 1 number of R 1C substituted by. In some embodiments, R 1A is an 8- to 10-membered bicyclic heteroaryl having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is r 1 number of R 1C substituted by. In some embodiments, R 1A is r 1 number of R 1C a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring substituted by. In some embodiments, R 1A is r 1 number of R 1C a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring substituted by. In some embodiments, R 1A is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is r 1 number of R 1C substituted by. In some embodiments, R 1A is a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is r 1 number of R 1C substituted by.

[0225] In some embodiments, R 1A is phenyl; naphthyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is r 1 number of R 1C substituted by. In some embodiments, R 1Ais a saturated or partially unsaturated monocyclic carbocyclic ring having 3 to 7 members; a saturated or partially unsaturated bicyclic carbocyclic ring having 5 to 12 members; a saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a saturated or partially unsaturated bicyclic heterocyclic ring having 7 to 12 members and having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is r 1 R 1C substituted by.

[0226] In some embodiments, R 1A is phenyl; naphthyl; a saturated or partially unsaturated monocyclic carbocyclic ring having 3 to 7 members; or a saturated or partially unsaturated bicyclic carbocyclic ring having 5 to 12 members, each of which is r 1 R 1C substituted by. In some embodiments, R 1A is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a saturated or partially unsaturated bicyclic heterocyclic ring having 7 to 12 members and having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is r 1 R 1C substituted by.

[0227] In some embodiments, R 1A is phenyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a saturated or partially unsaturated monocyclic carbocyclic ring having 3 to 7 members; or a saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is r 1 R 1C substituted by. In some embodiments, R1A is naphthyl; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is 1 substituted by r 1C number of Rs.

[0228] In some embodiments, R 1A is phenyl or naphthyl, each of which is 1 substituted by r 1C number of Rs. In some embodiments, R 1A is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is 1 substituted by r 1C number of Rs. In some embodiments, R 1A is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is 1 substituted by r 1C number of Rs. In some embodiments, R 1A is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is 1 substituted by r 1C number of Rs.

[0229] In some embodiments, R 1Ais a phenyl or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is r 1 R 1C substituted by. In some embodiments, R 1A is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is r 1 R 1C substituted by. In some embodiments, R 1A is naphthyl or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is r 1 R 1C substituted by. In some embodiments, R 1A is a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is r 1 R 1C substituted by.

[0230] In some embodiments, R 1A is phenyl or a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, each of which is r 1 R 1C substituted by. In some embodiments, R 1A is naphthyl or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is r 1 R 1C substituted by. In some embodiments, R 1Ais a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 3-7 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is 1 R 1C In some embodiments, R 1A is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is 1 R 1C is replaced by

[0231] In some embodiments, R 1A is C 1-6 an aliphatic chain; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocycle; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocycle; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is selected from r 1 R 1C In some embodiments, R 1A is C 1-6 an aliphatic chain; phenyl; naphthyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is 1 R 1C In some embodiments, R 1A is C 1-6An aliphatic chain; phenyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 1 number of Rs 1C is substituted by.

[0232] In some embodiments, R 1A is a C 1-6 aliphatic chain, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is substituted by r 1 number of Rs 1C is substituted by. In some embodiments, R 1A is a C 1-6 aliphatic chain, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 1 number of Rs 1C is substituted by. In some embodiments, R 1A is a C 1-6 aliphatic chain, phenyl, or a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, each of which is substituted by r 1 number of Rs 1C is substituted by.

[0233] In some embodiments, each R 1A is independently halogen, -CN, -OR, or a C 1 aliphatic chain substituted by r 1-6 number of halogens. In some embodiments, each R 1A is independently halogen, -CN, -OR, or a C 1-6 aliphatic chain substituted by 0 to 5 halogens. In some embodiments, each R 1A is independently halogen, -CN, -O-(a C substituted by 0 to 5 halogens1-6 an aliphatic chain), or C substituted with 0 to 5 halogens 1-6 is an aliphatic chain. In some embodiments, each R 1A is independently a halogen, or a C substituted with 0 to 5 halogens 1-6 is an aliphatic chain. In some embodiments, each R 1A is independently a halogen, or a C substituted with 0 to 4 halogens 1-6 is an aliphatic chain. In some embodiments, each R 1A is independently a halogen, or a C substituted with 0 to 3 halogens 1-6 is an aliphatic chain. In some embodiments, each R 1A is independently a halogen, or a C substituted with 0 to 3 halogens 1-3 is an aliphatic chain. In some embodiments, each R 1A is independently a halogen, or a C substituted with 0 to 2 halogens 1-3 is an aliphatic chain.

[0234] In some embodiments, each R 1A is independently a halogen selected from Br, Cl, and F. In some embodiments, each R 1A is independently a halogen selected from Cl and F. In some embodiments, R 1A is Cl. In some embodiments, R 1A is F.

[0235] In some embodiments, at least one R 1A is a halogen. In some embodiments, at least two R 1A are halogens. In some embodiments, at least three R 1A are halogens. In some embodiments, one of the R 1A is Cl. In some embodiments, two of the R 1A are Cl. In some embodiments, one of the R 1A is F. In some embodiments, R1A Two of them are F. In some embodiments, R 1A One of them is Cl, and R 1A One of them is F. In some embodiments, R 1A Two of them are Cl, and R 1A One of them is F. In some embodiments, R 1A One of them is Cl, and R 1A Two of them are F.

[0236] In some embodiments, R 1A is an aliphatic chain substituted with 0 to 5 halogens on C 1-6 In some embodiments, R 1A is an aliphatic chain substituted with 0 to 4 halogens on C 1-6 In some embodiments, R 1A is an aliphatic chain substituted with 0 to 3 halogens on C 1-6 In some embodiments, R 1A is an aliphatic chain substituted with 0 to 3 halogens on C 1-3 In some embodiments, R 1A is an aliphatic chain substituted with 0 to 2 halogens on C 1-3 In some embodiments, R

[0237] In some embodiments, at least one R 1A is an aliphatic C optionally substituted with 1 to 3 halogens 1-3 In some embodiments, at least one R 1A is an aliphatic -O-C optionally substituted with 1 to 3 halogens 1-3 In some embodiments, each R

[0238] In some embodiments, each R 1A is independently halogen, -OH, -OCH3, or an aliphatic C optionally substituted with 1 to 3 halogens 1-3 In some embodiments, each R 1A is independently fluorine, chlorine, -OCH3, or -CH3. In some embodiments, R1A is -OH. In some embodiments, R 1A is -CH3. In some embodiments, R 1A is -OCH3. In some embodiments, R 1A is -CF3. In some embodiments, R 1A is -CHF2.

[0239] In some embodiments, R 1A is selected from the groups shown in the compounds of Table 1.

[0240] As defined generally above, each R 2A is independently R 2 substituted by r 2C R A or R B In some embodiments, each R 2A is R A In some embodiments, each R 2A is R 2 substituted by r 2C R B is.

[0241] In some embodiments, R 2A is phenyl; naphthyl; cubanyl; adamantyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where R 2A is substituted by r 2 R 2C is.

[0242] In some embodiments, R 2A is phenyl; naphthyl; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 2A is r 2 number of R 2C substituted by. In some embodiments, R 2A is phenyl; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 2A is r 2 number of R 2C substituted by. In some embodiments, R 2A is phenyl or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 2A is r 2 number of R 2C substituted by.

[0243] In some embodiments, R 2A is phenyl; naphthyl; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 2Ais oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, and optionally substituted C 1-6 selected independently from r 2 groups. In some embodiments, R 2A is phenyl; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where R 2A is oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, and optionally substituted C 1-6 selected independently from r 2 groups. In some embodiments, R 2A is phenyl, or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where R 2Ais selected independently from oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, and optionally substituted C 1-6 selected independently from aliphatic r 2 is substituted by the group of.

[0244] In some embodiments, R 2A is r 2 number of R 2C is phenyl substituted by. In some embodiments, R 2A is selected independently from oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, and optionally substituted C 1-6 selected independently from aliphatic r 2 is phenyl substituted by the group of.

[0245] In some embodiments, R 2A is halogen, -CN, -O-(optionally substituted C 1-6 aliphatic), and optionally substituted C 1-6 is phenyl substituted by 1 to 3 groups selected independently from aliphatic. In some embodiments, R 2Ais phenyl substituted by halogen and 1 to 3 groups independently selected from optionally substituted C 1-3 aliphatic. In some embodiments, R 2A is phenyl substituted by 1 to 3 groups independently selected from fluorine, chlorine, -CH3, -CHF2, and -CF3.

[0246] In some embodiments, R 2A is halogen, -CN, -O-(optionally substituted C 1-6 aliphatic), and phenyl substituted by 2 groups independently selected from optionally substituted C 1-6 aliphatic. In some embodiments, R 2A is phenyl substituted by halogen and 2 groups independently selected from optionally substituted C 1-3 aliphatic. In some embodiments, R 2A is phenyl substituted by 2 groups independently selected from fluorine, chlorine, -CH3, -CHF2, and -CF3.

[0247] In some embodiments, R 2A is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where R 2A is r 2 number of R 2C substituted. In some embodiments, R 2A is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where R 2Ais selected independently from oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, and optionally substituted C 1-6 r selected independently from aliphatics 2 is substituted by the group of r

[0248] In some embodiments, R 2A is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where R 2A is r 2 r 2C is substituted by the group of R 2A In some embodiments, R 2A is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where R 1-6 is selected independently from oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2, and optionally substituted C 1-6 r selected independently from aliphatics 2 is substituted by the group of r

[0249] In some embodiments, R 2Ais an 8- to 10-membered bicyclic heteroaryl ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 2A is substituted by 0 to 2 groups independently selected from halogen, -CN, -O-(optionally substituted C 1-6 aliphatic), and optionally substituted C 1-6 aliphatic. In some embodiments, R 2A is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 2A is substituted by 0 to 2 groups independently selected from halogen and C 1-3 aliphatic optionally substituted with 1 to 3 halogens. In some embodiments, R 2A is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 2A is substituted by 0 to 2 groups independently selected from fluorine, chlorine, -CH3, -CHF2, and -CF3.

[0250] In some embodiments, R 2A is oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, or deuterium.

[0251] In some embodiments, R 2Ais oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0252] In some embodiments, R 2A is oxo. In some embodiments, R 2A is halogen. In some embodiments, R 2A is -CN. In some embodiments, R 2A is -NO2. In some embodiments, R 2A is -OR. In some embodiments, R 2A is -SR. In some embodiments, R 2A is -NR2. In some embodiments, R 2A is -S(O)2R. In some embodiments, R 2A is -S(O)2NR2. In some embodiments, R 2A is -S(O)2F. In some embodiments, R 2A is -S(O)R. In some embodiments, R 2A is -S(O)NR2. In some embodiments, R 2A is -S(O)(NR)R. In some embodiments, R 2A is -C(O)R. In some embodiments, R 2A is -C(O)OR. In some embodiments, R 2A is -C(O)NR2. In some embodiments, R 2A is -C(O)N(R)OR. In some embodiments, R 2Ais -OC(O)R. In some embodiments, R 2A is -OC(O)NR2. In some embodiments, R 2A is -N(R)C(O)OR. In some embodiments, R 2A is -N(R)C(O)R. In some embodiments, R 2A is -N(R)C(O)NR2. In some embodiments, R 2A is -N(R)C(NR)NR2. In some embodiments, R 2A is -N(R)S(O)2NR2. In some embodiments, R 2A is -N(R)S(O)2R. In some embodiments, R 2A is -P(O)R2. In some embodiments, R 2A is -P(O)(R)OR. In some embodiments, R 2A is -B(OR)2. In some embodiments, R 2A is deuterium.

[0253] In some embodiments, R 2A is halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0254] In some embodiments, R 2A is halogen, -CN, or -NO2. In some embodiments, R 2A is -OR, -SR, or -NR2. In some embodiments, R 2Ais -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 2A is -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, R 2A is -OC(O)R or -OC(O)NR2. In some embodiments, R 2A is -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, or -N(R)S(O)2R. In some embodiments, R 2A is -P(O)R2 or -P(O)(R)OR.

[0255] In some embodiments, R 2A is -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R 2A is -SR, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 2A is -NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, or -N(R)S(O)2R.

[0256] In some embodiments, R 2A is -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R 2A is -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 2A is -SR, -S(O)2R, or -S(O)R. In some embodiments, R 2A is -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 2Ais -S(O)2NR2 or -S(O)NR2. In some embodiments, R 2A is -SR, -S(O)2R, -S(O)2NR2, or -S(O)R.

[0257] In some embodiments, R 2A is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R 2A is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R 2A is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R 2A is -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R 2A is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0258] In some embodiments, R 2A is -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R 2A is -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R 2A is -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0259] In some embodiments, R 2A is C 1-6An aliphatic chain; phenyl; naphthyl; cubanyl; adamantyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is r 2 of r 2C substituted by

[0260] In some embodiments, R 2A is an aliphatic chain substituted by r 2 of r 2C C 1-6 In some embodiments, R 2A is phenyl substituted by r 2 of r 2C In some embodiments, R 2A is naphthyl substituted by r 2 of r 2C In some embodiments, R 2A is cubanyl substituted by r 2 of r 2C In some embodiments, R 2A is adamantyl substituted by r 2 of r 2C In some embodiments, R 2A is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is substituted by r 2 of r 2C In some embodiments, R 2Ais an 8- to 10-membered bicyclic heteroaryl having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is r 2 R 2C substituted by. In some embodiments, R 2A is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring substituted by r 2 R 2C . In some embodiments, R 2A is a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring substituted by r 2 R 2C . In some embodiments, R 2A is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is r 2 R 2C substituted by. In some embodiments, R 2A is a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is r 2 R 2C substituted by.

[0261] In some embodiments, R 2A is phenyl; naphthyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is r 2 R 2C substituted by. In some embodiments, R 2Ais cubanyl; adamantyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 2 of R 2C by.

[0262] In some embodiments, R 2A is phenyl; naphthyl; cubanyl; adamantyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is substituted by r 2 of R 2C by. In some embodiments, R 2A is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 2 of R 2C by.

[0263] In some embodiments, R 2A is phenyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 2 of R 2Cis replaced. In some embodiments, R 2A is naphthyl; cubanyl; adamantyl; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 2 number of R 2C .

[0264] In some embodiments, R 2A is phenyl or naphthyl, each of which is substituted by r 2 number of R 2C . In some embodiments, R 2A is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 2 number of R 2C . In some embodiments, R 2A is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is substituted by r 2 number of R 2C . In some embodiments, R 2A is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 2 number of R 2C .

[0265] In some embodiments, R 2Ais a phenyl or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 2 number of R 2C In some embodiments, R 2A is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 2 number of R 2C In some embodiments, R 2A is naphthyl or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 2 number of R 2C In some embodiments, R 2A is cubanyl; adamantyl; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 2 number of R 2C In some embodiments, R

[0266] In some embodiments, R 2A is phenyl or a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, each of which is substituted by r 2 number of R 2C In some embodiments, R 2A is naphthyl; cubanyl; adamantyl; or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is substituted by r 2 number of R 2C In some embodiments, R 2Ais a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 2 number of R 2C s. In some embodiments, R 2A is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 2 number of R 2C s.

[0267] In some embodiments, R 2A is a C 1-6 aliphatic chain; cubanyl; adamantyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 2 number of R 2C s. In some embodiments, R 2A is a C 1-6 aliphatic chain; phenyl; naphthyl; cubanyl; adamantyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is substituted by r 2 number of R 2C s. In some embodiments, R 2A is a C 1-6An aliphatic chain; phenyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 2 r 2C substituted by

[0268] In some embodiments, R 2A is 1-6 an aliphatic chain, cubanyl, adamantyl, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is substituted by r 2 r 2C substituted by. In some embodiments, R 2A is 1-6 an aliphatic chain, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 2 r 2C substituted by. In some embodiments, R 2A is 1-6 an aliphatic chain, phenyl, or a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, each of which is substituted by r 2 r 2C substituted by

[0269] In some embodiments, R 2A is selected from the groups shown in the compounds of Table 1

[0270] As defined generally above, each R TA is independently 3 r TC substituted by R A or R B In some embodiments, each R T is independently RA It is. In some embodiments, each R T is, independently, r 3 R's substituted with TC R B is.

[0271] In some embodiments, R TA is oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, or deuterium.

[0272] In some embodiments, R TA is oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0273] In some embodiments, R TA is oxo. In some embodiments, R TA is halogen. In some embodiments, R TA is -CN. In some embodiments, R TA is -NO2. In some embodiments, R TA is -OR. In some embodiments, R TAis -SR. In some embodiments, R TA is -NR2. In some embodiments, R TA is -S(O)2R. In some embodiments, R TA is -S(O)2NR2. In some embodiments, R TA is -S(O)2F. In some embodiments, R TA is -S(O)R. In some embodiments, R TA is -S(O)NR2. In some embodiments, R TA is -S(O)(NR)R. In some embodiments, R TA is -C(O)R. In some embodiments, R TA is -C(O)OR. In some embodiments, R TA is -C(O)NR2. In some embodiments, R TA is -C(O)N(R)OR. In some embodiments, R TA is -OC(O)R. In some embodiments, R TA is -OC(O)NR2. In some embodiments, R TA is -N(R)C(O)OR. In some embodiments, R TA is -N(R)C(O)R. In some embodiments, R TA is -N(R)C(O)NR2. In some embodiments, R TA is -N(R)C(NR)NR2. In some embodiments, R TA is -N(R)S(O)2NR2. In some embodiments, R TA is -N(R)S(O)2R. In some embodiments, R TA is -P(O)R2. In some embodiments, R TA is -P(O)(R)OR. In some embodiments, R TA is -B(OR)2. In some embodiments, R TA is deuterium.

[0274] In some embodiments, R TA is halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0275] In some embodiments, R TA is halogen, -CN, or -NO2. In some embodiments, R TA is -OR, -SR, or -NR2. In some embodiments, R TA is -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R TA is -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, R TA is -OC(O)R or -OC(O)NR2. In some embodiments, R TA is -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, or -N(R)S(O)2R. In some embodiments, R TA is -P(O)R2 or -P(O)(R)OR.

[0276] In some embodiments, R TA is -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R TAis -SR, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R TA is -NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, or -N(R)S(O)2R.

[0277] In some embodiments, R TA is -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R TA is -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R TA is -SR, -S(O)2R, or -S(O)R. In some embodiments, R TA is -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R TA is -S(O)2NR2 or -S(O)NR2. In some embodiments, R TA is -SR, -S(O)2R, -S(O)2NR2, or -S(O)R.

[0278] In some embodiments, R TA is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R TA is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R TA is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R TA is -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R TA is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0279] In some embodiments, R TA is -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R TA is -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R TA is -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0280] In some embodiments, R TA is C 1-6 an aliphatic chain; phenyl; naphthyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is 3 substituted by r TC number of Rs.

[0281] In some embodiments, R TA is 3 an aliphatic chain substituted by r TC number of Rs. In some embodiments, R 1-6 is phenyl substituted by r TA number of Rs. In some embodiments, R 3 is naphthyl substituted by r TC number of Rs. In some embodiments, R TA is 3 number of Rs TC substituted naphthyl. In some embodiments, R TAis a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is r 3 of R TC substituted by. In some embodiments, R TA is an 8- to 10-membered bicyclic heteroaryl having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is r 3 of R TC substituted by. In some embodiments, R TA is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring substituted by r 3 of R TC . In some embodiments, R TA is a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring substituted by r 3 of R TC . In some embodiments, R TA is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is r 3 of R TC substituted by. In some embodiments, R TA is a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the ring is r 3 of R TC substituted by.

[0282] In some embodiments, R TAis phenyl; naphthyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 3 r TC substituted by

[0283] In some embodiments, R TA is phenyl; naphthyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 3 r TC substituted by. In some embodiments, R TA is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 3 r TC substituted by

[0284] In some embodiments, R TA is phenyl; naphthyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is substituted by r 3 r TCis replaced. In some embodiments, R TA is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 3 number of R TC s.

[0285] In some embodiments, R TA is phenyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 3 number of R TC s. In some embodiments, R TA is naphthyl; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 3 number of R TC s.

[0286] In some embodiments, R TA is phenyl or naphthyl, each of which is substituted by r 3 number of R TC s. In some embodiments, R TAis a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 3 number of R TC is substituted by. In some embodiments, R TA is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is substituted by r 3 number of R TC is substituted by. In some embodiments, R TA is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 3 number of R TC is substituted by.

[0287] In some embodiments, R TA is phenyl or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 3 number of R TC is substituted by. In some embodiments, R TA is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 3 number of R TC is substituted by. In some embodiments, R TA is naphthyl or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 3 number of R TC is substituted by. In some embodiments, RTA is a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is r 3 substituted by TC r

[0288] In some embodiments, R TA is phenyl or a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, each of which is r 3 substituted by TC r TA In some embodiments, R 3 is naphthyl or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is r TC substituted by TA r TC In some embodiments, R TA is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is r3 substituted by 3 r TC In some embodiments, R

[0289] In some embodiments, R TA is C 1-6An aliphatic chain; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 3 of R TC by. In some embodiments, R TA is a C 1-6 aliphatic chain; phenyl; naphthyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is substituted by r 3 of R TC by. In some embodiments, R TA is a C 1-6 aliphatic chain; phenyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 3 of R TC by.

[0290] In some embodiments, R TA is a C 1-6 aliphatic chain, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is substituted by r 3 of R TC by. In some embodiments, R TA is a C 1-6 aliphatic chain, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 3 of R TCis replaced by. In some embodiments, R TA is a C 1-6 aliphatic chain, phenyl, or a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, each of which is substituted by r 3 number of R TC .

[0291] In some embodiments, R TA is selected from the groups shown in the compounds of Table 1.

[0292] As defined generally above, each R L is independently R substituted by r 4 number of R LC or R A or R B . In some embodiments, each R L is independently R A . In some embodiments, each R L is independently R substituted by r 4 number of R LC B .

[0293] In some embodiments, R L is oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, or deuterium.

[0294] In some embodiments, R L ​is oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0295] In some embodiments, R L is oxo. In some embodiments, R L is halogen. In some embodiments, R L is -CN. In some embodiments, R L is -NO2. In some embodiments, R L is -OR. In some embodiments, R L is -SR. In some embodiments, R L is -NR2. In some embodiments, R L is -S(O)2R. In some embodiments, R L is -S(O)2NR2. In some embodiments, R L is -S(O)2F. In some embodiments, R L is -S(O)R. In some embodiments, R L is -S(O)NR2. In some embodiments, R L is -S(O)(NR)R. In some embodiments, R L is -C(O)R. In some embodiments, R L is -C(O)OR. In some embodiments, R L is -C(O)NR2. In some embodiments, R L is -C(O)N(R)OR. In some embodiments, R Lis -OC(O)R. In some embodiments, R L is -OC(O)NR2. In some embodiments, R L is -N(R)C(O)OR. In some embodiments, R L is -N(R)C(O)R. In some embodiments, R L is -N(R)C(O)NR2. In some embodiments, R L is -N(R)C(NR)NR2. In some embodiments, R L is -N(R)S(O)2NR2. In some embodiments, R L is -N(R)S(O)2R. In some embodiments, R L is -P(O)R2. In some embodiments, R L is -P(O)(R)OR. In some embodiments, R L is -B(OR)2. In some embodiments, R L is deuterium.

[0296] In some embodiments, R L is halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0297] In some embodiments, R L is halogen, -CN, or -NO2. In some embodiments, R L is -OR, -SR, or -NR2. In some embodiments, R Lis -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R L is -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, R L is -OC(O)R or -OC(O)NR2. In some embodiments, R L is -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, or -N(R)S(O)2R. In some embodiments, R L is -P(O)R2 or -P(O)(R)OR.

[0298] In some embodiments, R L is -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R L is -SR, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R L is -NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, or -N(R)S(O)2R.

[0299] In some embodiments, R L is -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R L is -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R L is -SR, -S(O)2R, or -S(O)R. In some embodiments, R L is -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R Lis -S(O)2NR2 or -S(O)NR2. In some embodiments, R L is -SR, -S(O)2R, -S(O)2NR2, or -S(O)R.

[0300] In some embodiments, R L is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R L is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R L is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R L is -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R L is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0301] In some embodiments, R L is -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R L is -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R L is -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0302] In some embodiments, R L is C 1-6An aliphatic chain; phenyl; naphthyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 4 of R LC by

[0303] In some embodiments, R L is 4 of R LC substituted C 1-6 aliphatic chain. In some embodiments, R L is 4 of R LC substituted phenyl. In some embodiments, R L is 4 of R LC substituted naphthyl. In some embodiments, R L is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is substituted by r 4 of R LC by L In some embodiments, R 4 is an 8- to 10-membered bicyclic heteroaryl having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is substituted by r LC of R L In some embodiments, R 4 is LCIt is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring substituted by L is a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring substituted by r 4 number of R LC is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is r L is substituted by number of R 4 number of R LC In some embodiments, R L is a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, where the ring is r 4 number of R TL is substituted by number of R

[0304] In some embodiments, R L is phenyl; naphthyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is r 4 number of R LC is substituted by number of R

[0305] In some embodiments, R Lis phenyl; naphthyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 4 number of Rs LC is substituted by. In some embodiments, R L is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 4 number of Rs LC is substituted by.

[0306] In some embodiments, R L is phenyl; naphthyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is substituted by r 4 number of Rs LC is substituted by. In some embodiments, R L is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 4 number of Rs LC is substituted by.

[0307] In some embodiments, R Lis phenyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 4 number of Rs LC In some embodiments, R L is naphthyl; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 4 number of Rs LC In some embodiments, R

[0308] is phenyl or naphthyl, each of which is substituted by r L number of Rs 4 In some embodiments, R LC is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r L number of Rs 4 In some embodiments, R LC is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is substituted by r L number of Rs 4 In some embodiments, R LC is substituted by. In some embodiments, R Lis a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 4 number of R LC and is substituted by.

[0309] In some embodiments, R L is phenyl or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 4 number of R LC and is substituted by. In some embodiments, R L is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 4 number of R LC and is substituted by. In some embodiments, R L is naphthyl or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 4 number of R LC and is substituted by. In some embodiments, R L is a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 4 number of R LC and is substituted by.

[0310] In some embodiments, R L is phenyl or a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, each of which is substituted by r 4 number of R LC and is substituted by. In some embodiments, RL is naphthyl or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is substituted by r 4 number of Rs LC In some embodiments, R L is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 4 number of Rs LC In some embodiments, R L is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 4 number of Rs LC In some embodiments, R

[0311] In some embodiments, R L is a C 1-6 aliphatic chain; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is substituted by r 4 number of Rs LC In some embodiments, R L is a C 1-6 aliphatic chain; phenyl; naphthyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is substituted by r 4 number of Rs LC In some embodiments, R L is a C1-6 An aliphatic chain; phenyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is 4 substituted by r LC as defined below.

[0312] In some embodiments, R L is a C 1-6 aliphatic chain, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring, each of which is 4 substituted by r LC as defined below. In some embodiments, R L is a C 1-6 aliphatic chain, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is 4 substituted by r LC as defined below. In some embodiments, R L is a C 1-6 aliphatic chain, phenyl, or a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, each of which is 4 substituted by r LC as defined below.

[0313] In some embodiments, R L is selected from the groups shown in the compounds of Table 1.

[0314] As defined generally above, R AEach of them is independently oxo, deuterium, halogen, -CN, -NO2, -OR, -SF5, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0315] In some embodiments, each R A is independently oxo, halogen, -CN, -NO2, -OR, -SF5, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0316] In some embodiments, each R A is oxo. In some embodiments, each R A is halogen. In some embodiments, each R A is -CN. In some embodiments, each R A is -NO2. In some embodiments, each R A is -OR. In some embodiments, each R A is -SF5. In some embodiments, each R A is -SR. In some embodiments, each R A is -NR2. In some embodiments, each R A is -S(O)2R. In some embodiments, each R Ais -S(O)2NR2. In some embodiments, R A is -S(O)2F. In some embodiments, R A is -S(O)R. In some embodiments, R A is -S(O)NR2. In some embodiments, R A is -S(O)(NR)R. In some embodiments, R A is -C(O)R. In some embodiments, R A is -C(O)OR. In some embodiments, R A is -C(O)NR2. In some embodiments, R A is -C(O)N(R)OR. In some embodiments, R A is -OC(O)R. In some embodiments, R A is -OC(O)NR2. In some embodiments, R A is -N(R)C(O)OR. In some embodiments, R A is -N(R)C(O)R. In some embodiments, R A is -N(R)C(O)NR2. In some embodiments, R A is -N(R)C(NR)NR2. In some embodiments, R A is -N(R)S(O)2NR2. In some embodiments, R A is -N(R)S(O)2R. In some embodiments, R A is -P(O)R2. In some embodiments, R A is -P(O)(R)OR. In some embodiments, R A is -B(OR)2. In some embodiments, R A is deuterium.

[0317] In some embodiments, R Ais halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0318] In some embodiments, R A is halogen, -CN, or -NO2. In some embodiments, R A is -OR, -SR, or -NR2. In some embodiments, R A is -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R A is -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, R A is -OC(O)R or -OC(O)NR2. In some embodiments, R A is -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, or -N(R)S(O)2R. In some embodiments, R A is -P(O)R2 or -P(O)(R)OR.

[0319] In some embodiments, R A is -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R A is -SR, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R Ais -NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, or -N(R)S(O)2R.

[0320] In some embodiments, R A is -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R A is -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R A is -SR, -S(O)2R, or -S(O)R. In some embodiments, R A is -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R A is -S(O)2NR2 or -S(O)NR2. In some embodiments, R A is -SR, -S(O)2R, -S(O)2NR2, or -S(O)R.

[0321] In some embodiments, R A is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R A is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R A is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R A is -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R A is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0322] In some embodiments, R A is -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R Ais -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R A is -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0323] In some embodiments, R A is selected from the groups shown in the compounds of Table 1.

[0324] As defined generally above, each R B is independently a C 1-6 aliphatic chain; phenyl; naphthyl; cubanyl; adamantyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0325] In some embodiments, R B is a C 1-6 aliphatic chain. In some embodiments, R B is phenyl. In some embodiments, R B is naphthyl. In some embodiments, R B is cubanyl. In some embodiments, R B is adamantyl. In some embodiments, R B is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R Bis an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring. In some embodiments, R B is a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring. In some embodiments, R B is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B is a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0326] In some embodiments, R B is phenyl; naphthyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0327] In some embodiments, R B is phenyl; naphthyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R Bis a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0328] In some embodiments, R B is phenyl; naphthyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring. In some embodiments, R B is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0329] In some embodiments, R B is phenyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B is naphthyl; an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0330] In some embodiments, R B is phenyl or naphthyl. In some embodiments, R B is a 5- or 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring. In some embodiments, R B is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0331] In some embodiments, R B is phenyl, or a 5- or 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B is naphthyl, or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B is a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0332] In some embodiments, R Bis phenyl or a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring. In some embodiments, R B is naphthyl or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring. In some embodiments, R B is a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0333] In some embodiments, R B is a C 1-6 aliphatic chain; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocyclic ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B is a C 1-6 aliphatic chain; phenyl; naphthyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring. In some embodiments, R B is a C 1-6 aliphatic chain; phenyl; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0334] In some embodiments, R B is a C 1-6 aliphatic chain, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring. In some embodiments, R B is a C 1-6 aliphatic chain, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B is a C 1-6 aliphatic chain, phenyl, or a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring.

[0335] In some embodiments, R B is selected from the groups shown in the compounds of Table 1.

[0336] As defined generally above, each of R 1C is independently oxo, deuterium, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, or a C 1-6 group optionally substituted from aliphatic, phenyl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0337] In some embodiments, R 1CEach of them is independently oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, or C 1-6 A group optionally substituted selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0338] In some embodiments, R 1C Each of them is independently oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2. In some embodiments, R 1C Each of them is independently C 1-6 A group optionally substituted selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0339] In some embodiments, R1C is oxo. In some embodiments, R 1C is deuterium. In some embodiments, R 1C each is independently halogen. In some embodiments, R 1C is -CN. In some embodiments, R 1C is -NO2. In some embodiments, R 1C is -OR. In some embodiments, R 1C is -SR. In some embodiments, R 1C is -NR2. In some embodiments, R 1C is -S(O)2R. In some embodiments, R 1C is -S(O)2NR2. In some embodiments, R 1C is -S(O)2F. In some embodiments, R 1C is -S(O)R. In some embodiments, R 1C is -S(O)NR2. In some embodiments, R 1C is -S(O)(NR)R. In some embodiments, R 1C is -C(O)R. In some embodiments, R 1C is -C(O)OR. In some embodiments, R 1C is -C(O)NR2. In some embodiments, R 1C is -C(O)N(R)OR. In some embodiments, R 1C is -OC(O)R. In some embodiments, R 1C is -OC(O)NR2. In some embodiments, R 1C is -N(R)C(O)OR. In some embodiments, R 1C is -N(R)C(O)R. In some embodiments, R 1C is -N(R)C(O)NR2. In some embodiments, R 1C is -N(R)C(NR)NR2. In some embodiments, R 1Cis -N(R)S(O)2NR2. In some embodiments, R 1C is -N(R)S(O)2R. In some embodiments, R 1C is -P(O)R2. In some embodiments, R 1C is -P(O)(R)OR. In some embodiments, R 1C is -B(OR)2.

[0340] In some embodiments, each R 1C is independently halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0341] In some embodiments, each R 1C is independently halogen, -CN, or -NO2. In some embodiments, each R 1C is independently -OR, -SR, or -NR2. In some embodiments, each R 1C is independently -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, each R 1C is independently -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, each R 1C is independently -OC(O)R or -OC(O)NR2. In some embodiments, each R 1CEach of them is independently -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, or -N(R)S(O)2R. In some embodiments, R 1C Each of them is independently -P(O)R2 or -P(O)(R)OR.

[0342] In some embodiments, R 1C Each of them is independently -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R 1C Each of them is independently -SR, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 1C Each of them is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, or -N(R)S(O)2R.

[0343] In some embodiments, R 1C Each of them is independently -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R 1C Each of them is independently -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 1C Each of them is independently -SR, -S(O)2R, or -S(O)R. In some embodiments, R 1C Each of them is independently -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 1C Each of them is independently -S(O)2NR2 or -S(O)NR2. In some embodiments, R 1C Each of them is independently -SR, -S(O)2R, -S(O)2NR2, or -S(O)R.

[0344] In some embodiments, R1C each of which is independently -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R 1C each of which is independently -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R 1C each of which is independently -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R 1C each of which is independently -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R 1C each of which is independently -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0345] In some embodiments, R 1C each of which is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R 1C each of which is independently -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R 1C each of which is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0346] In some embodiments, R 1C each of which is independently optionally substituted C 1-6 is aliphatic. In some embodiments, R 1C each of which is independently optionally substituted phenyl. In some embodiments, R 1C each of which is independently a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur and optionally substituted. In some embodiments, R 1CEach of them is, independently, an optionally substituted 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0347] In some embodiments, each of R 1C is, independently, an optionally substituted C 1-6 aliphatic, or an optionally substituted 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each of R 1C is, independently, an optionally substituted phenyl, or an optionally substituted 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0348] In some embodiments, each of R 1C is, independently, an optionally substituted C 1-6 aliphatic or an optionally substituted phenyl. In some embodiments, each of R 1C is, independently, an optionally substituted 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an optionally substituted 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0349] In some embodiments, each of R 1C is, independently, a group optionally substituted with a group selected from phenyl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0350] In some embodiments, each of R 1C is, independently, C1-6 It is aliphatic. In some embodiments, R 1C is phenyl. In some embodiments, each of R 1C is independently a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each of R 1C is independently a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0351] In some embodiments, each of R 1C is independently C 1-6 aliphatic, or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each of R 1C is independently phenyl, or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0352] In some embodiments, each of R 1C is independently C 1-6 aliphatic or phenyl. In some embodiments, each of R 1C is independently a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0353] In some embodiments, each of R 1C is independently phenyl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0354] In some embodiments, each R 1C is, independently, halogen, -CN, -O-(optionally substituted C 1-6 aliphatic), or optionally substituted C 1-6 aliphatic. In some embodiments, each R 1C is, independently, halogen, -CN, -O-(C 1-6 aliphatic), or C 1-6 aliphatic, where each C 1-6 aliphatic is optionally substituted with one or more halogen atoms. In some embodiments, each R 1C is, independently, halogen, or C 1-3 aliphatic optionally substituted with 1 to 3 halogens. In some embodiments, each R 1C is, independently, fluorine, chlorine, -CH3, -CHF2, or -CF3.

[0355] In some embodiments, each R 1C is, independently, oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, or optionally substituted C 1-6 aliphatic.

[0356] In some embodiments, each R 1C is, independently, selected from the groups shown in the compounds of Table 1.

[0357] As defined generally above, R 2CEach of which is independently oxo, deuterium, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, or C 1-6 A group optionally substituted from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0358] In some embodiments, R 2C Each of which is independently oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, or C 1-6 A group optionally substituted from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0359] In some embodiments, R 2CEach of which is independently oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2. In some embodiments, R 2C Each of which is independently selected from C 1-6 A 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an optionally substituted group selected from.

[0360] In some embodiments, R 2C Is oxo. In some embodiments, R 2C Is deuterium. In some embodiments, R 2C Each of which is independently halogen. In some embodiments, R 2C Is -CN. In some embodiments, R 2C Is -NO2. In some embodiments, R 2C Is -OR. In some embodiments, R 2C Is -SR. In some embodiments, R 2C Is -NR2. In some embodiments, R 2C Is -S(O)2R. In some embodiments, R 2C Is -S(O)2NR2. In some embodiments, R 2C Is -S(O)2F. In some embodiments, R 2C Is -S(O)R. In some embodiments, R 2Cis -S(O)NR2. In some embodiments, R 2C is -S(O)(NR)R. In some embodiments, R 2C is -C(O)R. In some embodiments, R 2C is -C(O)OR. In some embodiments, R 2C is -C(O)NR2. In some embodiments, R 2C is -C(O)N(R)OR. In some embodiments, R 2C is -OC(O)R. In some embodiments, R 2C is -OC(O)NR2. In some embodiments, R 2C is -N(R)C(O)OR. In some embodiments, R 2C is -N(R)C(O)R. In some embodiments, R 2C is -N(R)C(O)NR2. In some embodiments, R 2C is -N(R)C(NR)NR2. In some embodiments, R 2C is -N(R)S(O)2NR2. In some embodiments, R 2C is -N(R)S(O)2R. In some embodiments, R 2C is -P(O)R2. In some embodiments, R 2C is -P(O)(R)OR. In some embodiments, R 2C is -B(OR)2.

[0361] In some embodiments, R 2CEach of them is independently a halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0362] In some embodiments, each of R 2C is independently a halogen, -CN, or -NO2. In some embodiments, each of R 2C is independently -OR, -SR, or -NR2. In some embodiments, each of R 2C is independently -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, each of R 2C is independently -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, each of R 2C is independently -OC(O)R or -OC(O)NR2. In some embodiments, each of R 2C is independently -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, or -N(R)S(O)2R. In some embodiments, each of R 2C is independently -P(O)R2 or -P(O)(R)OR.

[0363] In some embodiments, each of R 2C is independently -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, each of R 2CEach of which is independently -SR, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 2C Each of which is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, or -N(R)S(O)2R.

[0364] In some embodiments, R 2C Each of which is independently -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R 2C Each of which is independently -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 2C Each of which is independently -SR, -S(O)2R, or -S(O)R. In some embodiments, R 2C Each of which is independently -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 2C Each of which is independently -S(O)2NR2 or -S(O)NR2. In some embodiments, R 2C Each of which is independently -SR, -S(O)2R, -S(O)2NR2, or -S(O)R.

[0365] In some embodiments, R 2C Each of which is independently -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R 2C Each of which is independently -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R 2C Each of which is independently -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R 2C Each of which is independently -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R 2CEach of them is independently -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0366] In some embodiments, each of R 2C is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, each of R 2C is independently -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, each of R 2C is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0367] In some embodiments, each of R 2C is independently optionally substituted C 1-6 is aliphatic. In some embodiments, each of R 2C is independently optionally substituted phenyl. In some embodiments, each of R 2C is independently an optionally substituted 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each of R 2C is independently an optionally substituted 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0368] In some embodiments, each of R 2C is independently optionally substituted C 1-6 is aliphatic, or an optionally substituted 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each of R 2CEach of them is independently a phenyl optionally substituted, or a 5- to 6-membered monocyclic heteroaryl ring optionally substituted and having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0369] In some embodiments, each of R 2C is independently an optionally substituted C 1-6 aliphatic or an optionally substituted phenyl. In some embodiments, each of R 2C is independently a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5- to 6-membered monocyclic heteroaryl ring optionally substituted and having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0370] In some embodiments, each of R 2C is independently a group optionally substituted and selected from a phenyl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0371] In some embodiments, each of R 2C is independently a C 1-6 aliphatic. In some embodiments, R 2C is a phenyl. In some embodiments, each of R 2C is independently a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each of R 2C is independently a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0372] In some embodiments, each R 2C is, independently, a C 1-6 aliphatic, or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each R 2C is, independently, phenyl, or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0373] In some embodiments, each R 2C is, independently, a C 1-6 aliphatic or phenyl. In some embodiments, each R 2C is, independently, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0374] In some embodiments, each R 2C is, independently, phenyl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0375] In some embodiments, each R 2C is, independently, halogen, -CN, -O-(optionally substituted C 1-6 aliphatic), or optionally substituted C 1-6 aliphatic. In some embodiments, each R 2C is, independently, halogen, -CN, -O-(C 1-6 aliphatic), or C 1-6 aliphatic, where each C 1-6 aliphatic is optionally substituted with one or more halogen atoms. In some embodiments, R2C Each of them is independently a halogen or a C optionally substituted with 1 to 3 halogens 1-3 that is aliphatic. In some embodiments, each of R 2C is independently fluorine, chlorine, -CH3, -CHF2, or -CF3.

[0376] In some embodiments, each of R 2C is independently oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, or a C optionally substituted with 1-6 an aliphatic.

[0377] In some embodiments, each of R 2C is independently (i) one or two groups independently selected from -O-(C 1-6 aliphatic), -OH, -N(C 1-6 aliphatic)2, and -CN, and (ii) a C optionally substituted with one, two, or three atoms independently selected from halogen and deuterium 1-6 that is aliphatic. In some embodiments, each of R 2C is independently (i) one or two groups independently selected from -O-(C 1-6 aliphatic), -OH, -N(C 1-6 aliphatic)2, and -CN, and (ii) a C optionally substituted with one, two, or three halogen atoms 1-6 that is aliphatic. In some embodiments, each of R 2C is independently -O-(C 1-6 aliphatic), -OH, -N(C 1-6C optionally substituted by one or two groups independently selected from aliphatic)2 and -CN 1-6 is aliphatic. In some embodiments, each of R 2C is independently C optionally substituted by 1, 2, or 3 atoms independently selected from halogen and deuterium 1-6 is aliphatic. In some embodiments, each of R 2C is independently C optionally substituted by 1, 2, or 3 atoms independently selected from halogen 1-6 is aliphatic.

[0378] In some embodiments, each of R 2C is independently oxo, deuterium, halogen, -CN, -OH, -O-(C 1-3 aliphatic), or C 1-3 is aliphatic, where each C 1-3 aliphatic is optionally substituted by one or more halogen atoms. In some embodiments, each of R 2C is independently oxo, deuterium, halogen, or -CN. In some embodiments, each of R 2C is independently oxo, -OH, -O-(C 1-3 aliphatic), or C 1-3 is aliphatic, where each C 1-3 aliphatic is optionally substituted by one or more halogen atoms. In some embodiments, each of R 2C is independently -O-(C 1-3 aliphatic) or C 1-3 is aliphatic, where each C 1-3 aliphatic is optionally substituted by one or more halogen atoms. In some embodiments, each of R 2C is independently -O-(C 1-3 aliphatic) or C 1-3 is aliphatic.

[0379] In some embodiments, each of R 2C is independently selected from the groups shown in the compounds of Table 1.

[0380] As defined generally above, each R TC is, independently, oxo, deuterium, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, or C 1-6 is an optionally substituted group selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0381] In some embodiments, each R TC is, independently, oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR)2, or C 1-6 is an optionally substituted group selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0382] In some embodiments, each R TC is, independently, oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2. In some embodiments, each R TC is, independently, a group optionally substituted from C 1-6 aliphatic, phenyl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0383] In some embodiments, R TC is oxo. In some embodiments, R TC is deuterium. In some embodiments, each R TC is, independently, halogen. In some embodiments, R TC is -CN. In some embodiments, R TC is -NO2. In some embodiments, R TC is -OR. In some embodiments, R TC is -SR. In some embodiments, R TC is -NR2. In some embodiments, R TC is -S(O)2R. In some embodiments, R TC is -S(O)2NR2. In some embodiments, R TC is -S(O)2F. In some embodiments, R TCis -S(O)R. In some embodiments, R TC is -S(O)NR2. In some embodiments, R TC is -S(O)(NR)R. In some embodiments, R TC is -C(O)R. In some embodiments, R TC is -C(O)OR. In some embodiments, R TC is -C(O)NR2. In some embodiments, R TC is -C(O)N(R)OR. In some embodiments, R TC is -OC(O)R. In some embodiments, R TC is -OC(O)NR2. In some embodiments, R TC is -N(R)C(O)OR. In some embodiments, R TC is -N(R)C(O)R. In some embodiments, R TC is -N(R)C(O)NR2. In some embodiments, R TC is -N(R)C(NR)NR2. In some embodiments, R TC is -N(R)S(O)2NR2. In some embodiments, R TC is -N(R)S(O)2R. In some embodiments, R TC is -P(O)R2. In some embodiments, R TC is -P(O)(R)OR. In some embodiments, R TC is -B(OR)2.

[0384] In some embodiments, R TCEach of them is independently a halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0385] In some embodiments, each of R TC is independently a halogen, -CN, or -NO2. In some embodiments, each of R TC is independently -OR, -SR, or -NR2. In some embodiments, each of R TC is independently -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, each of R TC is independently -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, each of R TC is independently -OC(O)R or -OC(O)NR2. In some embodiments, each of R TC is independently -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, or -N(R)S(O)2R. In some embodiments, each of R TC is independently -P(O)R2 or -P(O)(R)OR.

[0386] In some embodiments, each of R TC is independently -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, each of R TCEach is independently -SR, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R TC Each is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, or -N(R)S(O)2R.

[0387] In some embodiments, R TC Each is independently -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R TC Each is independently -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R TC Each is independently -SR, -S(O)2R, or -S(O)R. In some embodiments, R TC Each is independently -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R TC Each is independently -S(O)2NR2 or -S(O)NR2. In some embodiments, R TC Each is independently -SR, -S(O)2R, -S(O)2NR2, or -S(O)R.

[0388] In some embodiments, R TC Each is independently -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R TC Each is independently -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R TC Each is independently -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R TC Each is independently -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R TCEach is independently -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0389] In some embodiments, each of R TC is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, each of R TC is independently -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, each of R TC is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0390] In some embodiments, each of R TC is independently optionally substituted C 1-6 aliphatic. In some embodiments, each of R TC is independently optionally substituted phenyl. In some embodiments, each of R TC is independently a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur and being optionally substituted. In some embodiments, each of R TC is independently a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur and being optionally substituted.

[0391] In some embodiments, each of R TC is independently optionally substituted C 1-6 aliphatic, or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur and being optionally substituted. In some embodiments, each of R TCEach of them is, independently, optionally substituted phenyl or an optionally substituted 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0392] In some embodiments, each of R TC is, independently, optionally substituted C 1-6 aliphatic or optionally substituted phenyl. In some embodiments, each of R TC is, independently, an optionally substituted 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an optionally substituted 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0393] In some embodiments, each of R TC is, independently, a group optionally selected from phenyl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, which is optionally substituted.

[0394] In some embodiments, each of R TC is, independently, C 1-6 aliphatic. In some embodiments, R TC is phenyl. In some embodiments, each of R TC is, independently, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic ring having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each of R TC is, independently, a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0395] In some embodiments, each R TC is, independently, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from C 1-6 aliphatic, or nitrogen, oxygen, and sulfur. In some embodiments, each R TC is, independently, phenyl or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0396] In some embodiments, each R TC is, independently, C 1-6 aliphatic or phenyl. In some embodiments, each R TC is, independently, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0397] In some embodiments, each R TC is, independently, phenyl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0398] In some embodiments, each R TC is, independently, halogen, -CN, -O-(optionally substituted C 1-6 aliphatic), or optionally substituted C 1-6 aliphatic. In some embodiments, each R TC is, independently, halogen, -CN, -O-(C 1-6 aliphatic), or C 1-6 aliphatic, where each C 1-6 aliphatic is optionally substituted with one or more halogen atoms. In some embodiments, RTC Each of them is independently a halogen or a C optionally substituted with 1 to 3 halogens 1-3 which is aliphatic. In some embodiments, each of R TC is independently fluorine, chlorine, -CH3, -CHF2, or -CF3.

[0399] In some embodiments, each of R TC is independently one or two groups...

Claims

1. Structure below: 【Chemistry 1】 A compound represented by or a pharmaceutically acceptable salt thereof.

2. Structure below: 【Chemistry 2】 A compound represented by or a pharmaceutically acceptable salt thereof.

3. A pharmaceutical composition comprising the compound described in claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

4. A pharmaceutical composition comprising the compound described in claim 2 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

5. A pharmaceutical composition for use in inhibiting PI3Kα signaling activity in a target, comprising the compound described in claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

6. A pharmaceutical composition for use in inhibiting PI3Kα signaling activity in a target, comprising the compound described in claim 2 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

7. A pharmaceutical composition for use in the treatment of PI3Kα-mediated disorders in a subject, comprising the compound described in claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

8. A pharmaceutical composition for use in the treatment of PI3Kα-mediated disorders in a subject, comprising the compound described in claim 2 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

9. A pharmaceutical composition for use in the treatment of cell proliferation disorders in a subject, comprising the compound described in claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

10. A pharmaceutical composition for use in the treatment of cell proliferation disorders in a subject, comprising the compound described in claim 2 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

11. The pharmaceutical composition according to claim 9, wherein the cell proliferation disorder is cancer.

12. The pharmaceutical composition according to claim 11, wherein the cancer is breast cancer.

13. The pharmaceutical composition according to claim 11, wherein the cancer is ovarian cancer.

14. The pharmaceutical composition according to claim 13, wherein the ovarian cancer is clear cell ovarian carcinoma.

15. The pharmaceutical composition according to claim 10, wherein the cell proliferation disorder is cancer.

16. The pharmaceutical composition according to claim 15, wherein the cancer is breast cancer.

17. The pharmaceutical composition according to claim 15, wherein the cancer is ovarian cancer.

18. The pharmaceutical composition according to claim 17, wherein the ovarian cancer is clear cell ovarian carcinoma.

19. The aforementioned cancers include sarcomas, lung cancer, bronchial cancer, prostate cancer, breast cancer (including patients with sporadic breast cancer and Cowden's disease), pancreas, gastrointestinal cancer, colon cancer, rectal cancer, carcinoma, colon cancer, adenoma, colorectal adenoma, thyroid cancer, liver cancer, intrahepatic bile duct cancer, hepatocyte cancer, adrenal gland cancer, abdominal cancer, stomach cancer, glioma, glioblastoma, endometrium cancer, melanoma, kidney cancer, renal pelvis cancer, bladder cancer, uterine body cancer, cervix cancer, vaginal cancer, ovarian cancer (including clear cell ovarian cancer), multiple myeloma, esophageal cancer, leukemia, acute myeloid leukemia, and chronic myeloid cancer. A pharmaceutical composition according to claim 11, selected from leukemia, lymphocytic leukemia, myeloid leukemia, brain, brain cancer, oral cavity and pharynx, larynx, small intestine, non-Hodgkin lymphoma, choriocolonic adenoma, tumor, epithelial tumor, lymphoma, breast cancer, basal cell carcinoma, squamous cell carcinoma, actinic keratosis, neck, head, polycythemia vera, essential thrombocythemia, myelofibrosis with myeloid metaplasia, and Waldenström macroglobulinemia.

20. The aforementioned cancers include sarcomas, lung cancer, bronchial cancer, prostate cancer, breast cancer (including patients with sporadic breast cancer and Cowden's disease), pancreas, gastrointestinal cancer, colon cancer, rectal cancer, carcinoma, colon cancer, adenoma, colorectal adenoma, thyroid cancer, liver cancer, intrahepatic bile duct cancer, hepatocyte cancer, adrenal gland cancer, abdominal cancer, stomach cancer, glioma, glioblastoma, endometrium cancer, melanoma, kidney cancer, renal pelvis cancer, bladder cancer, uterine body cancer, cervix cancer, vaginal cancer, ovarian cancer (including clear cell ovarian cancer), multiple myeloma, esophageal cancer, leukemia, acute myeloid leukemia, and chronic myeloid cancer. A pharmaceutical composition according to claim 15, selected from leukemia, lymphocytic leukemia, myeloid leukemia, brain, brain cancer, oral cavity and pharynx, larynx, small intestine, non-Hodgkin lymphoma, choriocolonic adenoma, tumor, epithelial tumor, lymphoma, breast cancer, basal cell carcinoma, squamous cell carcinoma, actinic keratosis, neck, head, polycythemia vera, essential thrombocythemia, myelofibrosis with myeloid metaplasia, and Waldenström macroglobulinemia.

21. A pharmaceutical composition for use in the treatment of a disease or disorder in a subject, wherein the pharmaceutical composition comprises a compound according to claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle, wherein the disease or disorder is polycythemia vera, essential thrombocythemia, myelofibrosis with myeloid metaplasia, asthma, COPD, ARDS, PROS, PI3K-related hypergrowth syndrome, venous malformation, Loeffler syndrome, eosinophilic pneumonia, Parasitic infections (especially metazoans), including tropical eosinophilia; bronchopulmonary aspergillosis; polyarteritis nodosa, including Churg-Strauss syndrome; eosinophilic granuloma; eosinophil-related disorders affecting the airways caused by drug reactions; psoriasis; contact dermatitis; atopic dermatitis; alopecia multiplex; erythema multiforme; dermatitis herpetiformis; scleroderma; vitiligo; hypersensitivity vasculitis; urticaria; bullous pemphigoid; lupus erythematosus; pemphigus; acquired epidermolysis bullosa; autoimmune hematological disorders. Hemolytic anemia, aplastic anemia, erythrocytic anemia and idiopathic thrombocytopenia, systemic lupus erythematosus, polychondritis, Wegener's granulomatosis, dermatomyositis, chronic active hepatitis, myasthenia gravis, Stevens-Johnson syndrome, idiopathic sprue, autoimmune inflammatory bowel disease, ulcerative colitis and Crohn's disease, endocrine ophthalmopathy, Graves' disease, sarcoidosis, alveolitis, chronic hypersensitivity pneumonitis, multiple sclerosis, primary biliary cirrhosis, and bronchitis including anterior and posterior parts of the liver. A pharmaceutical composition selected from the group consisting of diseases characterized by increased intraocular pressure or aqueous humor secretion, such as dangitis, interstitial pulmonary fibrosis, psoriatic arthritis, glomerulonephritis, cardiovascular disease, atherosclerosis, hypertension, deep vein thrombosis, stroke, myocardial infarction, unstable angina, thromboembolism, pulmonary embolism, thrombolytic disease, acute arterial ischemia, peripheral thrombotic occlusion, coronary artery disease, reperfusion injury, retinopathy such as diabetic retinopathy or hyperbaric oxygen-induced retinopathy, and glaucoma.

22. A pharmaceutical composition for use in the treatment of a disease or disorder in a subject, wherein the pharmaceutical composition comprises a compound according to claim 2 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle, wherein the disease or disorder is polycythemia vera, essential thrombocythemia, myelofibrosis with myeloid metaplasia, asthma, COPD, ARDS, PROS, PI3K-related hypergrowth syndrome, venous malformation, Loeffler syndrome, eosinophilic pneumonia, Parasitic infections (especially metazoans), including tropical eosinophilia; bronchopulmonary aspergillosis; polyarteritis nodosa, including Churg-Strauss syndrome; eosinophilic granuloma; eosinophil-related disorders affecting the airways caused by drug reactions; psoriasis; contact dermatitis; atopic dermatitis; alopecia multiplex; erythema multiforme; dermatitis herpetiformis; scleroderma; vitiligo; hypersensitivity vasculitis; urticaria; bullous pemphigoid; lupus erythematosus; pemphigus; acquired epidermolysis bullosa; autoimmune hematological disorders. Hemolytic anemia, aplastic anemia, erythrocytic anemia and idiopathic thrombocytopenia, systemic lupus erythematosus, polychondritis, Wegener's granulomatosis, dermatomyositis, chronic active hepatitis, myasthenia gravis, Stevens-Johnson syndrome, idiopathic sprue, autoimmune inflammatory bowel disease, ulcerative colitis and Crohn's disease, endocrine ophthalmopathy, Graves' disease, sarcoidosis, alveolitis, chronic hypersensitivity pneumonitis, multiple sclerosis, primary biliary cirrhosis, and bronchitis including anterior and posterior parts of the liver. A pharmaceutical composition selected from the group consisting of diseases characterized by increased intraocular pressure or aqueous humor secretion, such as dangitis, interstitial pulmonary fibrosis, psoriatic arthritis, glomerulonephritis, cardiovascular disease, atherosclerosis, hypertension, deep vein thrombosis, stroke, myocardial infarction, unstable angina, thromboembolism, pulmonary embolism, thrombolytic disease, acute arterial ischemia, peripheral thrombotic occlusion, coronary artery disease, reperfusion injury, retinopathy such as diabetic retinopathy or hyperbaric oxygen-induced retinopathy, and glaucoma.

23. The pharmaceutical composition according to any one of claims 5 to 22, wherein the subject has PI3Kα containing at least one mutation from H1047R, E542K, and E545K.

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