PI3K-α inhibitors and their usage

Abstract

This application relates to PI3K-α inhibitors and methods of using them. This disclosure relates to novel compounds and pharmaceutical compositions thereof, as well as methods of inhibiting PI3K-α enzyme activity using the compounds and compositions of this disclosure. This disclosure further relates to, but is not limited to, methods of treating conditions related to PI3K-α signaling using the compounds and compositions of this disclosure.

Description

[0001] This application relates to a divisional application of the invention patent application filed on April 29, 2021, with application number 202180043509.2 and entitled "PI3K-α inhibitor and method of use thereof".

[0002] Cross-reference of related applications

[0003] This application claims the benefits of U.S. Provisional Application No. 63 / 017,571, filed April 29, 2020, and U.S. Provisional Application No. 63 / 066,489, filed August 17, 2020, the entire contents of each of which are incorporated herein by reference. Technical Field

[0004] This application relates to PI3K-α inhibitors and their methods of use. Background Technology

[0005] Phosphatidylinositol 3-kinase (PI3K) belongs to the lipid kinase family that catalyzes the transfer of phosphate esters to the D-3' position of inositol esters to produce phosphoinositol-3-phosphate (PIP), phosphoinositol-3,4-diphosphate (PIP2), and phosphoinositol-3,4,5-triphosphate (PIP3). These products then act as second messengers in the signal cascade by introducing proteins containing the pleckstrin-homology domain, FYVE, Phox, and other phospholipid-binding domains into various signal transduction complexes normally located at the plasma membrane (Vanhaesebroeck et al., Annals of Biochemistry 70:535 (2001); Katso et al., Annals of Cell and Developmental Biology 17:615 (2001)). In the two class 1 PI3K subclasses, class 1A PI3Ks are heterodimers composed of catalytic p110 subunits (α, β, or δ isoforms) constitutively associated with the regulatory subunits, which can be p85α, p55α, p50α, p85β, or p55γ. The class 1B subclass has a family member consisting of heterodimers composed of catalytic p110γ subunits associated with one of the two regulatory subunits, p101 or p84 (Fruman et al., Annals of Biochemistry 67:481 (1998); Suire et al., Curr. Biol. 15:566 (2005)). The modular domains of the p85 / 55 / 50 subunits include a Src homology (SH2) domain, which binds to phosphotyrosine residues in a specific sequence background on the activated receptor and cytoplasmic tyrosine kinase, leading to activation and localization of class 1A PI3Ks. Class 1B PI3K is directly activated by binding to a variety of peptide and non-peptide ligands of G protein-coupled receptors (Stephens et al., Cell 89:105 (1997); Katso et al., Annals of Cell and Developmental Biology 17:615-675 (2001)).

[0006] Therefore, the phospholipid products derived from class I PI3K link upstream receptors to downstream cellular activities, including proliferation, survival, chemotaxis, cell migration, motility, metabolism, inflammation 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 Aid (the product of a human homolog of the viral oncogene v-Akt) to the plasma membrane, where Aid acts as a node in many intracellular signaling pathways that are important for growth and survival (Vant et al., Cell 69:413-423 (1992); Bader et al., Nature Review Cancer 5:921 (2005); Vivanco and Sawyer, Nature Review Cancer 2:489 (2002)).

[0007] Aberrant regulation of PI3K, which typically enhances survival through Aid activation, is one of the most prevalent phenomena in human cancer and has been shown to occur at multiple levels. The tumor suppressor gene PTEN, which dephosphorylates phosphoinositol at the 3' position of the inositol ring and thus antagonizes PI3K activity, is functionally lost in various tumors. In other tumors, the genes of the p110α isoforms PIK3CA and Akt are amplified, and increased protein expression of their gene products has been demonstrated in several human cancers. Furthermore, mutations and translocations of p85α that regulate the p85-p110 complex have been described in human cancers. Finally, somatic missense mutations in PIK3CA, which have been described with significant frequency in various human cancers activating downstream signaling pathways (Kang et al., 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 suggest that dysregulation of phosphoinositol-3 kinase and its upstream and downstream components is one of the most common dysregulations associated with human cancers and proliferative diseases (Parsons et al., Nature 436:792 (2005); Hennessey et al., Nature Review Drug Disc. 4:988-1004 (2005)).

[0008] Given the above, PI3Kα inhibitors will have particular value in the treatment of proliferative diseases and other conditions. While various PI3K inhibitors have been developed (e.g., taselisib, alpelisib, buparlisib, and others), these molecules inhibit multiple class 1A PI3K isoforms. Inhibitors active against multiple class 1A PI3K isoforms are called “pan-PI3K” inhibitors. A major obstacle in the clinical development of existing PI3K inhibitors is the inability to achieve the desired target inhibition levels in tumors while avoiding toxicity to cancer patients. Pan-PI3K inhibitors share certain target-related toxicities, including diarrhea, rash, fatigue, and hyperglycemia. The toxicity of PI3K inhibitors depends on their isoform selectivity profile. Inhibition of PI3Kα is associated with hyperglycemia and rash, while inhibition of PI3Kδ or PI3Kγ is associated with diarrhea, myelosuppression, and elevated transaminases (Hanker et al., Cancer Discovery (2019) PMID:30837161). Therefore, selective inhibitors of PI3Kα could increase the therapeutic window, enabling adequate target inhibition in tumors while avoiding dose-limiting toxicities in cancer patients. Summary of the Invention

[0009] In some embodiments, this disclosure provides compounds of formula I-1:

[0010]

[0011] Or a pharmaceutically acceptable salt thereof, wherein R 1 R 2 Each of Q, E, X, Y, and Z is as defined in the embodiments and categories and subclasses herein.

[0012] In some embodiments, the present invention provides compounds of formula I:

[0013]

[0014] Or a pharmaceutically acceptable salt thereof, wherein R 1 R 2 Each of Q, E, X, Y, and Z is as defined in the embodiments and categories and subclasses herein.

[0015] In some embodiments, the present invention provides a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, adjuvant, or diluent.

[0016] In some embodiments, the present invention provides a method for treating PI3Kα-mediated conditions, comprising administering a compound of formula I or a composition comprising said compound to a patient in need.

[0017] In some embodiments, the present invention provides a method for providing a compound of formula I or a synthetic intermediate thereof.

[0018] In some embodiments, the present invention provides a method for providing a pharmaceutical composition comprising a compound of formula I. Detailed Implementation

[0019] General description of certain embodiments of the present invention

[0020] The compounds and pharmaceutical compositions thereof of the present invention are suitable as PI3Kα inhibitors. In some embodiments, the present invention provides compounds of formula I:

[0021]

[0022] Or its pharmaceutically acceptable salt, wherein:

[0023] E is -C(O)-, -C(R) E )2-、-C(R E )2C(R E )2-、-C(S)-、-S(O) 2- -OC(O)-, -N(R) E )C(O)-、-C(O)N(R E - or -C(R) E )2C(O)-;

[0024] Q represents CH, C(R) Q ) or N;

[0025] X represents CH, C(R) X ) or N;

[0026] Y represents CH, C(R) Y ) or N;

[0027] Z represents CH, C(R) Z ) or N;

[0028] R 1 -L 1 -R 1A ;

[0029] R 2 -L 2 -R 2A ;

[0030] R E Each instance is independently H or -LE -R EA ;

[0031] R Q -L Q -R QA ;

[0032] R X -L X -R XA ;

[0033] R Y -L Y -R YA ;

[0034] R Z -L Z -R ZA ;or

[0035] R E Two instances, together with their equivalent inserted atoms, form 3 to 8-membered saturated or partially unsaturated monocyclic rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 8 to 12-membered saturated or partially unsaturated bicyclic rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein each ring is R EEC Replace n instances;

[0036] R Q and R 1 Together with the inserted atoms, they form a 4- to 8-membered saturated or partially unsaturated monocyclic ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 12-membered saturated or partially unsaturated bicyclic ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein each ring is R Q1C Replace p instances;

[0037] R Y and R Z Together with the inserted atoms, they form a 4- to 7-membered partially unsaturated or aromatic ring having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, and sulfur; wherein the ring is R YZC Replace q instances;

[0038] L 1 L 2 L E L Q L X L Y and L Z Each of them is independently a covalent bond, or C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(RL )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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-;

[0039] R 1A For R 1C r 1 Instances replace R A Or R B ;

[0040] R 2A For R 2C r 2 Instances replace R A Or R B ;

[0041] R EA For R EC r 3 Instances replace R A Or R B ;

[0042] R QA For R QC r 4 Instances replace R A Or R B ;

[0043] R XA For R XC r 5 Instances replace R A Or R B ;

[0044] R YA For R YC r 6 Instances replace R A Or R B ;

[0045] R ZA For R ZC r 7 Instances replace R A Or R B ;

[0046] R L For R LC r8 Instances replace R A Or R B ;

[0047] R A Each instance is independently an oxo group, 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;

[0048] R B Each instance is independently C 1-6 Aliphatic chain; phenyl; naphthyl; cubic; 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 carbon ring; 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 7- to 12-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

[0049] R 1C R 2C R EC R QC R XC R YC R ZC R LC R EEC R Q1C and R YZCEach instance is independently an oxo group, 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 an optionally substituted group selected from the following: C 1-6 Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0050] Each instance of R is independently hydrogen or a substituted group selected from the following: C 1-6 Aliphatic group, phenyl group, 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 5- to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or

[0051] Two R groups on the same nitrogen atom, together with their equivalent intercalated atoms, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 independent heteroatoms selected from nitrogen, oxygen, and sulfur, in addition to the nitrogen atom; and

[0052] n, p, q, r 1 r 2 r 3 r 4 r 5 r 6 r 7 and r 8 Each of them is independently 0, 1, 2, 3 or 4.

[0053] Compounds and definitions

[0054] The compounds of this invention include those generally described herein and further illustrated by the categories, subclasses and species disclosed herein. Unless otherwise specified, the following definitions shall apply as used herein. For the purposes of this invention, chemical elements are identified according to the Periodic Table of the Elements, CAS edition, Handbook of Chemistry and Physics, 75th edition. Furthermore, the general principles of organic chemistry are described in “Organic Chemistry”, Thomas Sorrell, University Science Books, Sausalito: 1999 and “March’s Advanced Organic Chemistry”, 5th edition, edited by Michael B. Smith (MB) and Jerry March (J.), John Wiley & Sons, New York: 2001, the entire contents of which are hereby incorporated by reference.

[0055] As used herein, the terms "aliphatic" or "aliphatic group" mean a fully saturated or branched linear (i.e., unbranched) or branched hydrocarbon chain containing one or more unsaturated units, or a fully saturated or non-aromatic monocyclic or bicyclic hydrocarbon (also referred to herein as "carbocyclic," "cycloaliphatic," or "cycloalkyl") having a single connection point to the rest of the molecule. Unless otherwise stated, an aliphatic group contains 1 to 6 aliphatic carbon atoms. In some embodiments, an aliphatic group contains 1 to 5 aliphatic carbon atoms. In other embodiments, an aliphatic group contains 1 to 4 aliphatic carbon atoms. In other embodiments, an aliphatic group contains 1 to 3 aliphatic carbon atoms, and in yet another embodiment, an aliphatic group contains 1 to 2 aliphatic carbon atoms. In some embodiments, "cycloaliphatic" (or "carbocyclic") refers to a fully saturated or non-aromatic monocyclic C3-C6 hydrocarbon containing one or more unsaturated units, having a single connection point to the rest of the molecule. Suitable aliphatic groups include, but are not limited to, straight or branched chains, substituted or unsubstituted alkyl, alkenyl, alkynyl and mixtures thereof, such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl.

[0056] Unless otherwise specified, as used herein, the term "alkyl" refers to a monovalent aliphatic hydrocarbon group having a straight chain, a branched chain, a monocyclic moiety, a polycyclic moiety, or a combination thereof, wherein said group is optionally substituted at one or more carbon atoms of the straight chain, branched chain, monocyclic moiety, polycyclic moiety, or a combination thereof by one or more substituents at each carbon atom, wherein said one or more substituents are independently C1-C. 10 Alkyl. Examples of "alkyl" include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl and similar groups.

[0057] The term "low-carbon alkyl" refers to C 1-4 Straight-chain or branched-chain alkyl groups. Exemplary low-carbon alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl.

[0058] The term "low-carbon haloalkyl" refers to a C-aryl group that has been substituted with one or more halogen atoms. 1-4 Straight-chain or branched-chain alkyl groups.

[0059] The term "heteroatom" means one or more of oxygen, sulfur, nitrogen, phosphorus, or silicon (including: any oxidized form of nitrogen, sulfur, phosphorus, or silicon; any quaternized form of basic nitrogen; or a substituted nitrogen of a heterocycle, such as N (e.g., in 3,4-dihydro-2H-pyrrole), NH (e.g., in pyrrolealkyl), or NR). + (e.g., in N-substituted pyrroleyl groups).

[0060] As used in this paper, the term "unsaturated" means that a part has one or more unsaturated units.

[0061] As used in this article, the term "C" 1-8 (or C) 1-6 Or C 1-4 "Saturated or unsaturated, straight or branched divalent hydrocarbon chains" refers to straight or branched divalent alkylene, alkenylene, and ynylene chains as defined herein.

[0062] The term "alkylene" refers to a divalent alkyl group. An "alkylene chain" is a polymethylene group, i.e., -(CH2). n - where 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 in which one or more methylene hydrogen atoms are replaced by substituents. Suitable substituents include those described below with respect to substituted aliphatic groups.

[0063] The term "alkenyl" refers to a divalent alkenyl group. The substituted alkenyl chain is a polymethylene containing at least one double bond and one or more hydrogen atoms replaced by a substituent. Suitable substituents include those described below with respect to substituted aliphatic groups.

[0064] The term "halogen" means F, Cl, Br, or I.

[0065] The term "aryl" as used alone or as part of a larger portion of "aralkyl," "arylalkoxy," 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 wherein each ring in the system contains 3 to 7 ring members. The term "aryl" may be used interchangeably with the term "aryl ring." In some embodiments of the invention, "aryl" refers to an aryl ring system that may have one or more substituents, including (but not limited to) phenyl, biphenyl, naphthyl, anthracene, and similar groups.

[0066] Unless otherwise defined, as used herein, the terms "heteroaryl" or "heteroaromatic" refer to a 5- or 6-membered monocyclic aromatic ring containing one or more heteroatoms (e.g., one to three heteroatoms, such as nitrogen, oxygen, and sulfur), or an 8- or 10-membered polycyclic ring system containing one or more heteroatoms, wherein at least one ring in the polycyclic ring system is aromatic, and the connection point of the polycyclic ring system is via a ring atom on an aromatic ring. The heteroaryl ring may be connected to an adjacent group via carbon or nitrogen. Examples of heteroaryl rings include (but are not limited to) furans, thiophenes, pyrroles, thiazoles, oxazoles, isothiazoles, isoxazoles, imidazoles, pyrazoles, triazoles, pyridines, pyrimidines, indoles, etc. For example, unless otherwise defined, 1,2,3,4-tetrahydroquinoline is a heteroaryl ring provided that its connection point is via a benzo[a] ring, for example:

[0067]

[0068] Unless otherwise defined, the term "heterocyclic group" or "heterocyclic ring" refers to a saturated or partially unsaturated 3- to 10-membered monocyclic or 7- to 14-membered polycyclic ring system, including bridging or fused rings, and whose ring system comprises one to four heteroatoms, such as nitrogen, oxygen, and sulfur. The heterocyclic ring may be connected to an adjacent group via carbon or nitrogen.

[0069] Unless otherwise defined, the term "partially unsaturated" in the context of rings refers to a constituent ring within a monocyclic or polycyclic (e.g., bicyclic, tricyclic, etc.) ring system, wherein the constituent ring contains at least one degree of unsaturation in addition to the degree of unsaturation provided by the ring itself, but is not aromatic. Examples of partially unsaturated rings include (but are not limited to) 3,4-dihydro-2H-pyran, 3-pyrrololine, 2-thiazoline, etc. When the 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, but the junction of the polycyclic ring system is located on the partially unsaturated constituent ring. For example, unless otherwise defined, 1,2,3,4-tetrahydroquinoline is a partially unsaturated ring, provided that its junction is via a piperidinyl ring, for example:

[0070]

[0071] Unless otherwise defined, the term "saturated" in the context of rings refers to a 3- to 10-membered monocyclic or 7- to 14-membered polycyclic (e.g., bicyclic, tricyclic, etc.) ring system, wherein the monocyclic ring or the constituent ring serving as the junction of the polycyclic ring system does not contain any additional unsaturation beyond that provided by the ring itself. Examples of monocyclic saturated rings include, but are not limited to, azahexacyclic butane, oxacyclic butane, cyclohexane, etc. In cases where the 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, but the junction of the polycyclic ring system is located on the saturated constituent ring. For example, unless otherwise defined, 2-azaspiro[3.4]octyl-6-ene is a saturated ring, provided that its junction is via an N-azahexacyclic butyl ring, for example:

[0072]

[0073] As used herein, the terms “alkylene,” “arylene,” “cycloalkylene,” “heteroarylene,” “heterocycloalkylene,” and other similar terms with the prefix “alkyl-” refer to the divalent bond form of the group modified by said prefix. For example, “alkylene” is a divalent alkyl group that links the group to its bond.

[0074] As used herein, the term "bridged bicyclic" refers to any bicyclic system having at least one bridging bond, i.e., a carbocyclic or heterocyclic system, saturated or partially unsaturated. As defined by IUPAC, a "bridging bond" is an unbranched chain of multiple atoms or a single atom, or a valence bond connecting two bridgeheads, wherein a "bridgehead" is any skeletal atom of a ring system bonded to three or more skeletal atoms (other than 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 those set forth below, wherein each group is attached to the remainder of the molecule at any substituted carbon or nitrogen atom. Unless otherwise specified, the bridged bicyclic group is optionally substituted with one or more substituents as described with respect to aliphatic groups. Additionally or alternatively, any substituted nitrogen atom in the bridged bicyclic group may optionally be substituted. Exemplary bridged bicyclics include:

[0075]

[0076] As described herein, the compounds of the present invention may contain an "optionally substituted" portion. Generally, the term "substituted," whether or not preceded by the term "optionally," means that one or more hydrogens of the indicated portion are replaced by suitable substituents. Unless otherwise indicated, the "optionally substituted" group may have suitable substituents at each substituted position of the group, and the substituents at each position may be the same or different when more than one position in any given structure can be substituted by more than one substituent selected from the specified group. The combinations of substituents contemplated in this invention are preferably combinations that form stable or chemically viable compounds. As used herein, the term "stable" means a compound that does not substantially change when subjected to conditions permissible for its production, detection, and, in some embodiments, recovery, purification, and use for one or more of the purposes disclosed herein.

[0077] The suitable monovalent substituent on the substituted carbon atom of the "optionally substituted" group is independently a 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- 4SR°;-(CH2) 0-4 Ph, which can be replaced by R°; -(CH2) 0-4 O(CH2) 0-1 Ph, which can be substituted by R°; -CH=CHPh, which can be substituted by R°; -(CH2) 0-4 O(CH2) 0-1 -Pyridyl group, which can 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) 0-4 N(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) 0-4OC(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)ON(R°)2; or -(C 1-4 (straight-chain or branched-chain alkylene)C(O)ON(R°)2, wherein each R° can be substituted as defined below and is independently hydrogen, C 1-6 Aliphatic groups, -CH2Ph, -O(CH2) 0-1 Ph, -CH2- (5 to 6-membered heteroaryl ring) or a 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 one or more inserted atoms to 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, which may be substituted as defined below.

[0078] Suitable monovalent substituents on R° (or a ring formed by two independently occurring R° atoms linked together with their equivalent insertion atoms) are independently halogens, -(CH2). 0-2 R ● -(halogenated R) ● -(CH2) 0-2 OH, -(CH2) 0-2 OR ● -(CH2) 0-2 CH(OR ● )2;-O(halogenated R ●-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 (straight-chain or branched-chain alkylene)C(O)OR ● or -SSR ● , where each R ● It is either unsubstituted or, if preceded by a "halogen group," substituted by only one or more halogens, and independently selected from 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. Suitable divalent substituents for the saturated carbon atom of R° include =O and =S.

[0079] Suitable divalent substituents on the saturated carbon atom of the "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 R * Each instance is independently selected from hydrogen, and can be replaced by C as defined below. 1-6 An aliphatic group, or an unsubstituted 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur. Suitable divalent substituents attached to the adjacent substituted carbon of the "optionally substituted" group include: -O(CR * 2) 2-3 O-, where R* Each instance is independently selected from hydrogen, and can be replaced by C as defined below. 1-6 Aliphatic group, 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.

[0080] R * Suitable substituents on the aliphatic group include halogens, -R ● -(halogenated R) ● -OH, -OR ● -O(halogenated R) ● -CN, -C(O)OH, -C(O)OR ● -NH2, -NHR ● -NR ● 2 or -NO2, where each R ● It is either unsubstituted or, when it has a "halogen group" before it is substituted by only one or more halogens, and is independently C. 1-4 Aliphatic groups, -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.

[0081] Suitable substituents on the substituted nitrogen of the "optionally substituted" group include or Among them each Independently hydrogen; C that can be substituted as defined below. 1-6 Aliphatic group; unsubstituted -OPh; or unsubstituted 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur; or, regardless of the above definitions, two independently occurring... Together with one or more inserted atoms, it forms an unsubstituted 3 to 12-membered saturated, partially unsaturated, or aryl monocyclic or bicyclic ring having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, or sulfur.

[0082] Suitable substituents on the aliphatic group are independently halogens, -R ● -(halogenated R) ● -OH, -OR ● -O(halogenated R) ● -CN, -C(O)OH, -C(O)OR ● -NH2, -NHR ● -NR ● 2 or -NO2, where each R ● It is either unsubstituted or, when it has a "halogen group" before it is substituted by only one or more halogens, and is independently C.1-4 Aliphatic groups, -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.

[0083] As used herein, the term "isomer" refers to a compound having the same chemical formula but different structural or optical configurations. As used herein, the term "stereoisomer" refers to and includes isomers having the same molecular formula but different spatial orientations of atoms and / or functional groups. All stereoisomers of the compounds of the present invention (e.g., those stereoisomers that may exist due to asymmetric carbons on the various substituents), including enantiomers and diastereomers, are covered within the scope of this disclosure. Therefore, unless otherwise stated, single stereochemical isomers of the compounds of the present invention, as well as mixtures of enantiomers, diastereomers, and geometric (or conformational) isomers, are within the scope of the present invention.

[0084] As used herein, the term "tautomer" refers to one of two or more structural isomers that exist in equilibrium and readily transform from one isomer to another. It should be understood that tautomers encompass valence tautomers and proton tautomers (also known as proton-transfer tautomers). Valence tautomers include interconversions via some recombination of bond electrons. Proton tautomers include interconversions via proton migration, such as keto-enol and imine-enamine isomerization. Unless otherwise stated, all tautomers of the compounds of this invention are within the scope of this invention.

[0085] As used herein, the term "isotope substitution" refers to the substitution of an atom by its isotope. As used herein, the term "isotope" refers to an atom that has the same number of atoms as the predominant atom found in nature, but whose mass number (number of neutrons) differs from that of the predominant atom found in nature. It should be understood that a compound with isotope substitution is a compound in which at least one atom is substituted by its isotope. Atoms that can be substituted by their isotopes include (but are not limited to) hydrogen, carbon, and oxygen. Examples of hydrogen isotopes include... 2 H (also represented as D) and 3 H. Examples of carbon isotopes include 13 C and 14 C. Examples of oxygen isotopes include 18 O. Unless otherwise stated, all isotopic substitutions of the compounds of this invention are within the scope of this invention. Such compounds are suitable as, for example, analytical tools, probes in bioanalysis, or therapeutic agents according to the invention. In some embodiments, for example, the warhead portion R of the provided compound... W It contains one or more deuterium atoms.

[0086] As used herein, the term “pharmaceutically acceptable salt” means that salts which, within the bounds of reasonable medical judgment, are suitable for contact with tissues of humans and lower animals without adverse toxicity, irritation, allergic reactions and similar effects, and in proportion to 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, PL., Int. J. Pharmaceutics 1986, 33, 201-217; (each incorporated herein by reference in its entirety).

[0087] Pharmaceutically acceptable salts of the compounds of this invention include salts derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable non-toxic acid addition salts are salts formed by amino groups with inorganic acids (e.g., hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid) or organic acids (e.g., acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid), or salts formed by other methods used in the art (e.g., ion exchange). Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, hydrogen sulfate, borate, butyrate, camphorate, camphor sulfonate, citrate, cyclopentanepropionate, disglucuronate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucono-heptahydrate, glyceryl phosphate, gluconate, hemisulfate, heptahydrate, hexanoate, hydroiodate, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, dihydroxynaphthalate, pectate, persulfate, 3-phenylpropionate, phosphate, p-pentanoate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, and similar salts.

[0088] Salts derived from suitable bases include alkali metal salts, alkaline earth metal salts, ammonium salts, and N salts. + (C 1-4 Alkyl)4 salts. Representative alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and similar salts. Other pharmaceutically acceptable salts include (where appropriate) non-toxic ammonium, quaternary ammonium, and amine cations formed using relative ions (e.g., halide, hydroxide, carboxyl, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate).

[0089] Pharmaceutically acceptable salts are also intended to include hemisalts, wherein the compound-to-acid ratio is 2:1. Exemplary hemisalts are those 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 those derived from diprotic mineral acids (e.g., sulfuric acid). Preferred exemplary hemisalts include (but are not limited to) hemimaleates, hemifumarates, and hemisuccinates.

[0090] As used herein, the term “about” is used to mean approximately, roughly, around, or near. When the term “about” is used in conjunction with a numerical range, its range is adjusted by extending the boundary of the stated value upwards or downwards. Generally, the term “about” is used herein to modify values ​​that are above or below the stated value: a deviation of 20% upwards or downwards (higher or lower).

[0091] As used herein, “effective amount,” “adequate amount,” or “therapeutic effective amount” is an amount of compound sufficient to achieve a beneficial or desired outcome (including clinical outcomes). Therefore, an effective amount may be sufficient, for example, to reduce or improve the severity and / or duration of a disorder related to PI3Kα signaling or one or more of its symptoms; to prevent the progression of symptoms or signs associated with a disorder related to PI3Kα signaling; or to enhance or otherwise improve the preventive or therapeutic effects of another therapy. An effective amount also includes an amount of compound that avoids or substantially reduces undesired side effects.

[0092] As used herein and as understood in the art, “treatment” is a method of achieving a beneficial or desired outcome (including clinical outcomes). Beneficial or desired clinical outcomes may include (but are not limited to) relief or improvement of one or more symptoms or ailments, reduction of the severity of disease or ailment, stabilization of the state of disease or ailment (i.e., no worsening), prevention of the spread of disease or ailment, delay or slowing of the progression of disease or ailment, improvement or mitigation of the state of disease or ailment, and relief (whether partial or complete), whether detectable or undetectable. “Treatment” may also mean an extension of survival compared to expected survival without treatment. In some embodiments, treatment may be administered after one or more symptoms have been present. In other embodiments, treatment may be administered when symptoms are absent. For example, treatment may be administered to susceptible individuals before the onset of symptoms (e.g., based on a history of symptoms and / or based on genetic or other susceptibility factors). Treatment may also continue after symptoms have subsided, for example, to prevent or delay their recurrence.

[0093] The phrase “required” means that symptomatic or asymptomatic relief is required from symptoms associated with PI3Kα signaling activity, or that relief can be achieved in other ways by the compounds and / or compositions of the present invention.

[0094] Description of exemplary embodiments

[0095] As described above, in some embodiments, the present invention provides compounds of formula I-1:

[0096]

[0097] Or its pharmaceutically acceptable salt, wherein:

[0098] E is -C(O)-, -C(R) E )2-、-C(R E )2C(R E )2-, -C(S)-, -S(O)2-, -OC(O)-, -N(R E )C(O)-、-C(O)N(R E - or -C(R) E )2C(O)-;

[0099] Q represents CH, C(R) Q ) or N;

[0100] X represents CH, C(R) X ) or N;

[0101] Y represents CH, C(R) Y ) or N;

[0102] Z represents CH, C(R) Z ) or N;

[0103] R 1 -L 1 -R 1A ;

[0104] R 2 -L 2 -R 2A ;

[0105] R E Each instance is independently H or -L E -R EA ;

[0106] R Q -L Q -R QA ;

[0107] R X -L X -R XA ;

[0108] R Y -L Y -R YA ;

[0109] R Z -LZ -R ZA ;or

[0110] R E Two instances, together with their equivalent inserted atoms, form 3 to 8-membered saturated or partially unsaturated monocyclic rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 8 to 12-membered saturated or partially unsaturated bicyclic rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein each ring is R EEC Replace n instances;

[0111] R Q and R 1 Together with the inserted atoms, they form a 4- to 8-membered saturated or partially unsaturated monocyclic ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 12-membered saturated or partially unsaturated bicyclic ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein each ring is R Q1C Replace p instances;

[0112] R Y and R Z Together with its intercalated atoms, it forms a 4- to 7-membered partially unsaturated or aromatic ring having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, and sulfur; wherein the ring is R YZC Replace q instances;

[0113] L 1 L 2 L E L Q L X L Y and L Z Each of them is independently a covalent bond, or C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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-;

[0114] R 1A For R 1C r 1 Instances replace R A Or RB ;

[0115] R 2A For R 2C r 2 Instances replace R A Or R B ;

[0116] R EA For R EC r 3 Instances replace R A Or R B ;

[0117] R QA For R QC r 4 Instances replace R A Or R B ;

[0118] R XA For R XC r 5 Instances replace R A Or R B ;

[0119] R YA For R YC r 6 Instances replace R A Or R B ;

[0120] R ZA For R ZC r 7 Instances replace R A Or R B ;

[0121] R L For R LC r 8 Instances replace R A Or R B ;

[0122] R AEach instance is independently an oxo group, 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)NR 2. -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;

[0123] R B Each instance is independently C 1-6 Aliphatic chain; phenyl; naphthyl; cubic; 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 carbon ring; 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 7- to 12-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

[0124] R 1C R 2C R EC R QC R XC R YC R ZC R LC R EEC R Q1C and R YZC Each instance is independently an oxo group, 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 an optionally substituted group selected from the following: C1-6 Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0125] Each instance of R is independently hydrogen or a substituted group selected from the following: C 1-6 Aliphatic group, phenyl group, 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 5- to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or

[0126] Two R groups on the same nitrogen atom, together with their equivalent intercalated atoms, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 independent heteroatoms selected from nitrogen, oxygen, and sulfur, in addition to the nitrogen atom; and

[0127] n, p, q, r 1 r 2 r 3 r 4 r 5 r 6 r 7 and r 8 Each of them is independently 0, 1, 2, 3, 4 or 5.

[0128] In some embodiments, the present invention provides a compound of formula I-1, wherein E, Q, X, Y, Z, R 1 R 2 R E R Q R X R Y R Z R 1A R 2A R EA R QA R XA R YA R ZA R L R A R B R 1C R 2C R EC R QC R XC R YC R ZC R LC R EEC R Q1C R YZC R, n, p, q, r 1r 2 r 3 r 4 r 5 r 6 r 7 and r 8 Each of these, as defined below and described in the embodiments herein, may be used individually or in combination.

[0129] In some embodiments, R YA It can be -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -S(O)(NCN)R, or -S(NCN)R. In some embodiments, R YA It can be -S(O)(NR)R, -S(O)(NCN)R, or -S(NCN)R. In some embodiments, R YA It is -S(O)(NCN)R or -S(NCN)R. In some embodiments, R YA For -S(O)(NCN)R. In some embodiments, R YA For -S(NCN)R. In some embodiments, R YA The groups are selected from those described in the compounds in Table 1.

[0130] In some embodiments, R A It can be -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -S(O)(NCN)R, or -S(NCN)R. In some embodiments, R A It can be -S(O)(NR)R, -S(O)(NCN)R, or -S(NCN)R. In some embodiments, R A It is -S(O)(NCN)R or -S(NCN)R. In some embodiments, R A For -S(O)(NCN)R. In some embodiments, R A For -S(NCN)R. In some embodiments, R A The groups are selected from those described in the compounds in Table 1.

[0131] In some embodiments, n is 1, 2, 3, 4, or 5. In some embodiments, n is 2, 3, 4, or 5. In some embodiments, n is 3, 4, or 5. In some embodiments, n is 4 or 5. In some embodiments, n is 5. In some embodiments, n is selected from the values ​​represented by the compounds in Table 1.

[0132] In some embodiments, p is 1, 2, 3, 4, or 5. In some embodiments, p is 2, 3, 4, or 5. In some embodiments, p is 3, 4, or 5. In some embodiments, p is 4 or 5. In some embodiments, p is 5. In some embodiments, p is selected from the values ​​represented by the compounds in Table 1.

[0133] In some embodiments, q is 1, 2, 3, 4, or 5. In some embodiments, q is 2, 3, 4, or 5. In some embodiments, q is 3, 4, or 5. In some embodiments, q is 4 or 5. In some embodiments, q is 5. In some embodiments, q is selected from the values ​​represented by the compounds in Table 1.

[0134] In some embodiments, r 1 It can be 1, 2, 3, 4, or 5. In some embodiments, r 1 It can be 2, 3, 4, or 5. In some embodiments, r 1 It is 3, 4, or 5. In some embodiments, r 1 It is 4 or 5. In some embodiments, r 1 The value is 5. In some embodiments, r 1 The values ​​are represented by the compounds selected from Table 1.

[0135] In some embodiments, r 2 It can be 1, 2, 3, 4, or 5. In some embodiments, r 2 It can be 2, 3, 4, or 5. In some embodiments, r 2 It is 3, 4, or 5. In some embodiments, r 2 It is 4 or 5. In some embodiments, r 2 The value is 5. In some embodiments, r 2 The values ​​are represented by the compounds selected from Table 1.

[0136] In some embodiments, r 3 It can be 1, 2, 3, 4, or 5. In some embodiments, r 3 It can be 2, 3, 4, or 5. In some embodiments, r 3 It is 3, 4, or 5. In some embodiments, r 3 It is 4 or 5. In some embodiments, r 3 The value is 5. In some embodiments, r 3 The values ​​are represented by the compounds selected from Table 1.

[0137] In some embodiments, r 4 It can be 1, 2, 3, 4, or 5. In some embodiments, r 4 It can be 2, 3, 4, or 5. In some embodiments, r 4 It is 3, 4, or 5. In some embodiments, r 4It is 4 or 5. In some embodiments, r 4 The value is 5. In some embodiments, r 4 The values ​​are represented by the compounds selected from Table 1.

[0138] In some embodiments, r 5 It can be 1, 2, 3, 4, or 5. In some embodiments, r 5 It can be 2, 3, 4, or 5. In some embodiments, r 5 It is 3, 4, or 5. In some embodiments, r 5 It is 4 or 5. In some embodiments, r 5 The value is 5. In some embodiments, r 5 The values ​​are represented by the compounds selected from Table 1.

[0139] In some embodiments, r 6 It can be 1, 2, 3, 4, or 5. In some embodiments, r 6 It can be 2, 3, 4, or 5. In some embodiments, r 6 It is 3, 4, or 5. In some embodiments, r 6 It is 4 or 5. In some embodiments, r 6 The value is 5. In some embodiments, r 6 The values ​​are represented by the compounds selected from Table 1.

[0140] In some embodiments, r 7 It can be 1, 2, 3, 4, or 5. In some embodiments, r 7 It can be 2, 3, 4, or 5. In some embodiments, r 7 It is 3, 4, or 5. In some embodiments, r 7 It is 4 or 5. In some embodiments, r 7 The value is 5. In some embodiments, r 7 The values ​​are represented by the compounds selected from Table 1.

[0141] In some embodiments, r 8 It can be 1, 2, 3, 4, or 5. In some embodiments, r 8 It can be 2, 3, 4, or 5. In some embodiments, r 8 It is 3, 4, or 5. In some embodiments, r 8 It is 4 or 5. In some embodiments, r 8 The value is 5. In some embodiments, r 8 The values ​​are represented by the compounds selected from Table 1.

[0142] As described above, in some embodiments, the present invention provides compounds of formula I:

[0143]

[0144] Or its pharmaceutically acceptable salt, wherein:

[0145] E is -C(O)-, -C(R) E )2-、-C(R E )2C(R E )2-、-C(S)-、-S(O) 2- -OC(O)-, -N(R) E )C(O)-、-C(O)N(R E - or -C(R) E )2C(O)-;

[0146] Q represents CH, C(R) Q ) or N;

[0147] X represents CH, C(R) X ) or N;

[0148] Y represents CH, C(R) Y ) or N;

[0149] Z represents CH, C(R) Z ) or N;

[0150] R 1 -L 1 -R 1A ;

[0151] R 2 -L 2 -R 2A ;

[0152] R E Each instance is independently H or -L E -R EA ;

[0153] R Q -L Q -R QA ;

[0154] R X -L X -R XA ;

[0155] R Y -L Y -R YA ;

[0156] R Z -L Z -R ZA ;or

[0157] R ETwo instances, together with their equivalent inserted atoms, form 3 to 8-membered saturated or partially unsaturated monocyclic rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 8 to 12-membered saturated or partially unsaturated bicyclic rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein each ring is R EEC Replace n instances;

[0158] R Q and R 1 Together with the inserted atoms, they form a 4- to 8-membered saturated or partially unsaturated monocyclic ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 12-membered saturated or partially unsaturated bicyclic ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein each ring is R Q1C Replace p instances;

[0159] R Y and R Z Together with its intercalated atoms, it forms a 4- to 7-membered partially unsaturated or aromatic ring having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, and sulfur; wherein the ring is R YZC Replace q instances;

[0160] L 1 L 2 L E L Q L X L Y and L Z Each of them is independently a covalent bond, or C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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-;

[0161] R 1A For R 1C r 1 Instances replace R A Or R B ;

[0162] R 2A For R 2C r2 Instances replace R A Or R B ;

[0163] R EA For R EC r 3 Instances replace R A Or R B ;

[0164] R QA For R QC r 4 Instances replace R A Or R B ;

[0165] R XA For R XC r 5 Instances replace R A Or R B ;

[0166] R YA For R YC r 6 Instances replace R A Or R B ;

[0167] R ZA For R ZC r 7 Instances replace R A Or R B ;

[0168] R L For R LC r 8 Instances replace R A Or R B ;

[0169] R A Each instance is independently an oxo group, 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;

[0170] R B Each instance is independently C 1-6 Aliphatic chain; phenyl; naphthyl; cubic; 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 carbon ring; 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 7- to 12-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

[0171] R 1C R 2C R EC R QC R XC R YC R ZC R LC R EEC R Q1C and R YZC Each instance is independently an oxo group, 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 an optionally substituted group selected from the following: C 1-6 Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0172] Each instance of R is independently hydrogen or a substituted group selected from the following: C 1-6 Aliphatic group, phenyl group, 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 5- to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or

[0173] Two R groups on the same nitrogen atom, together with their equivalent intercalated atoms, form a 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having 0 to 3 independent heteroatoms selected from nitrogen, oxygen, and sulfur, in addition to the nitrogen atom; and

[0174] n, p, q, r 1 r 2 r 3 r 4 r 5 r 6 r 7 and r 8 Each of them is independently 0, 1, 2, 3 or 4.

[0175] As generally defined above, E is -C(O)-, -C(R)-. E )2-、-C(R E )2C(R E )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -C(S)-, -S(O)2-, -OC(O)-, -N(R) E )C(O)-、-C(O)N(R E - or -C(R) E )2C(O)-. In some embodiments, E is -C(O)-. In some embodiments, E is -OC(O)- or -N(R)-. E )C(O)-. In some embodiments, E is -C(R) E ) 2- C 3-6 Cycloalkyl or C 3-6 Heterocyclic alkyl groups.

[0176] In some embodiments, E is -C(O)-, -OC(O)-, or -N(R). E C(O)- or -C(R) E )2C(O)-. In some embodiments, E is -OC(O)-, -N(R)-. E C(O)- or -C(R) E )2C(O)-. In some embodiments, E is -C(O)- or -N(R)-. E )C(O)-.

[0177] In some embodiments, E is -C(O)- or -C(R)-. E -C(S)- or -S(O)2-. In some embodiments, E is -C(O)- or -C(R)2-. E E is -C(O)- or -C(S)-. In some embodiments, E is -C(O)- or -C(S)-.

[0178] In some embodiments, E is -C(R) E )2C(R E )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -OC(O)-, -N(R) E )C(O)-、-C(O)N(R E - or -C(R) E )2C(O)-. In some embodiments, E is C 3-6 Cycloalkyl or C 3-6 Heterocyclic alkyl group. In some embodiments, E is -C(R E )2C(R E )2-、-OC(O)-、-N(R E )C(O)-、-C(O)N(R E - or -C(R) E )2C(O)-. In some embodiments, E is -OC(O)-, -N(R)-. E )C(O)-、-C(O)N(R E - or -C(R) E )2C(O)-. In some embodiments, E is -OC(O)-, -N(R)-. E C(O)- or -C(O)N(R) E In some embodiments, E is -N(R) E C(O)- or -C(O)N(R) E In some embodiments, E is -N(H)C(O)- or -C(O)N(H)-. In some embodiments, E is -N(CH3)C(O)- or -C(O)N(CH3)-.

[0179] In some embodiments, E is -S(O). 2- -OC(O)-, -N(R) E C(O)- or -C(O)N(R) E In some embodiments, E is -C(O)- or -C(R). E )2-、-C(R E )2C(R E )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -C(S)- or -C(R) E )2C(O)-. In some embodiments, E is -C(O)-, -C(R)-. E )2-、-C(R E )2C(R E )2-、-C(S)- or -C(R) E)2C(O)-. In some embodiments, E is -C(O)-, -C(S)-, or -C(R)-. E )2C(O)-. In some embodiments, E is -C(R) E )2-、-C(R E )2C(R E )2- or -C(R E )2C(O)-. In some embodiments, E is -C(R) E )2- or -C(R E )2C(R E )2-.

[0180] In some embodiments, E is -C(R) E )2-. In some embodiments, E is -C(R) E )2C(R E )2-. In some embodiments, E is C 3-6 Cycloalkylene. In some embodiments, E is C 3-6 Heterocyclic alkyl group. In some embodiments, E is -C(S)-. In some embodiments, E is -S(O). 2- In some embodiments, E is -OC(O)-. In some embodiments, E is -N(R)-. E E is -N(H)C(O)-. In some embodiments, E is -N(CH3)C(O)-. In some embodiments, E is -C(O)N(R)-. E In some embodiments, E is -C(O)N(H)-. In some embodiments, E is -C(O)N(CH3)-. In some embodiments, E is -C(R)-. E )2C(O)-.

[0181] In some embodiments, E is selected from the groups depicted in the compounds in Table 1.

[0182] As generally defined above, Q is CH, C(R) Q ) or N. In some embodiments, Q is CH. In some embodiments, Q is C(R) Q In some embodiments, Q is N. In some embodiments, Q is CH or C(R). Q In some embodiments, Q is CH or N. In some embodiments, Q is C(R). Q ) or N. In some embodiments, Q is selected from the groups depicted in the compounds in Table 1.

[0183] As generally defined above, X is CH, C(R) X X is either ) or N. In some embodiments, X is CH. In some embodiments, X is C(R)X In some embodiments, X is N. In some embodiments, X is CH or C(R). X In some embodiments, X is CH or N. In some embodiments, X is C(R) X X is selected from the groups depicted in the compounds in Table 1.

[0184] As generally defined above, Y is CH, C(R) Y ) or N. In some embodiments, Y is CH. In some embodiments, Y is C(R) Y In some embodiments, Y is N. In some embodiments, Y is CH or C(R) Y In some embodiments, Y is CH or N. In some embodiments, Y is C(R). Y () or N. In some embodiments, Y is selected from the groups depicted in the compounds in Table 1.

[0185] As generally defined above, Z represents CH, C(R) Z Z is either Z or N. In some embodiments, Z is CH. In some embodiments, Z is C(R) Z In some embodiments, Z is N. In some embodiments, Z is CH or C(R). Z In some embodiments, Z is CH or N. In some embodiments, Z is C(R). Z () or N. In some embodiments, Z is selected from the groups depicted in the compounds in Table 1.

[0186] As generally defined above, R 1 -L 1 -R 1A Or R Q and R 1 Together with the inserted atoms, they form a 4- to 8-membered saturated or partially unsaturated monocyclic ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 12-membered saturated or partially unsaturated bicyclic ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein each ring is R Q1C p instances are replaced. In some embodiments, R 1 -L 1 -R 1A In some embodiments, R 1 -R 1A .

[0187] In some embodiments, R Q and R 1Together with the inserted atoms, they form a 4- to 8-membered saturated or partially unsaturated monocyclic ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 12-membered saturated or partially unsaturated bicyclic ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein each ring is R Q1C p instances are replaced. In some embodiments, R Q and R 1 Together with the inserted atoms, they form a 4- to 8-membered saturated or partially unsaturated monocyclic ring having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, and sulfur; wherein the ring is R Q1C p instances are replaced. In some embodiments, R Q and R 1 Together with its intercalated atoms, it forms an 8- to 12-membered saturated or partially unsaturated bicyclic ring having 0 to 4 independently selected heteroatoms from nitrogen, oxygen, and sulfur; wherein the ring is R Q1C Replace p instances.

[0188] In some embodiments, R 1 (i.e. -L) 1 -R 1A Together) Where R 1C and r 1 As defined in the embodiments and categories and subclasses herein. In some embodiments, R 1 (i.e. -L) 1 -R 1A Together) Where R 1C As defined in the embodiments and categories and subclasses herein. In some embodiments, R 1 (i.e. -L) 1 -R 1A Together) Where R 1C As defined in the embodiments and categories and subclasses herein. In some embodiments, R 1 (i.e. -L) 1 -R 1A Together) Where R 1C As defined in the embodiments and categories and subclasses herein. In some embodiments, R 1 (i.e. -L) 1 -R 1A Together) Where R 1C As defined in the embodiments, categories, and subclasses described herein.

[0189] In some embodiments, R 1 (i.e. -L) 1 -R 1A Together) Where R 1C Each instance is independently a halogen, -CN, -O- (optionally substituted C). 1-6 (Aliphatic group) or optionally substituted C 1-6 Aliphatic group. In some embodiments, R 1 (i.e. -L) 1 -R 1A Together) Where R 1C Each instance is independently a halogen or optionally a C substituted with one to three halogens. 1-3 Aliphatic group. In some embodiments, R 1 (i.e. -L) 1 -R 1A Together) Where R 1C Each instance is independently a halogen or optionally a C substituted with one to three halogens. 1-3 Aliphatic group. In some embodiments, R 1 (i.e. -L) 1 -R 1A Together) Where R 1C Each instance is independently a halogen or optionally a C substituted with one to three halogens. 1-3 Aliphatic group. In some embodiments, R 1 (i.e. -L) 1 -R 1A Together) Where R 1C Each instance is independently fluorine, chlorine, -CH3, -CHF2, or -CF3. In some embodiments, R 1 (i.e. -L) 1 -R 1A Together) Where R 1C C is a halogen or optionally substituted with 1 to 3 halogens. 1-3 Aliphatic groups.

[0190] In some embodiments, R 1 (i.e. -L) 1 -R 1A Together) In some embodiments, R 1 (i.e. -L) 1 -R 1A Together)

[0191] In some embodiments, R 1 (i.e. -L) 1 -R 1A Together) Where R1C and r 1 As defined in the embodiments and categories and subclasses herein. In some embodiments, R 1 (i.e. -L) 1 -R 1A Together) In some embodiments, R 1 (i.e. -L) 1 -R 1A Together) In some embodiments, R 1 (i.e. -L) 1 -R 1A Together)

[0192] In some embodiments, R 1 The groups are selected from those described in the compounds in Table 1.

[0193] As generally defined above, R 2 -L 2 -R 2A In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) is -N(R)C(O)-R 2A or -R 2A , where R and R 2A As defined in the embodiments and categories and subclasses herein. In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) is -N(R)C(O)-R 2A , where R and R 2A As defined in the embodiments and categories and subclasses herein. In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) is -N(H)C(O)-R 2A , where R 2A As defined in the embodiments and categories and subclasses herein. In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) is -N(H)C(O)-R 2A , where R 2A For R 2C r 2 Instances replace R B In some embodiments, R 2 -R 2A .

[0194] In some embodiments, R 2 -N(H)C(O)-R 2A -N(H)C(O)N(H)-R 2A -C(O)N(H)-R 2A -N(H)-R 2A -S(O)2CH2-R 2A -CH2S(O)2-R 2A Or -C(H)(CH3)OH. In some embodiments, R 2 -N(H)C(O)-R 2A -N(H)C(O)N(H)-R 2A or -N(H)-R 2A In some embodiments, R 2 -C(O)N(H)-R 2A -CH2S(O)2-R 2A Or -C(H)(CH3)OH. In some embodiments, R 2 -S(O)2CH2-R 2A or -CH2S(O)2-R 2A .

[0195] In some embodiments, R 2 -N(H)C(O)N(H)-R 2A In some embodiments, R 2 -C(O)N(H)-R 2A In some embodiments, R 2 -N(H)-R 2A In some embodiments, R 2 -S(O)2CH2-R 2A In some embodiments, R 2 -CH2S(O)2-R 2A In some embodiments, R 2 It is -C(H)(CH3)OH.

[0196] In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C and r 2 As defined in the embodiments and categories and subclasses herein. In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C As defined in the embodiments, categories, and subclasses described herein.

[0197] In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C Each instance is independently a halogen, -CN, -O- (optionally substituted C). 1-6 (Aliphatic group) or optionally substituted C 1-6 Aliphatic group. In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C Each instance is independently a halogen or optionally a C substituted with one to three halogens. 1-3 Aliphatic group. In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C Each instance is independently fluorine, chlorine, -CH3, -CHF2, or -CF3. In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) In some embodiments, R 2 (i.e. -L) 2 -R 2A Together)

[0198] In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C and r 2 As defined in the embodiments and categories and subclasses herein. In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C As defined in the embodiments, categories, and subclasses described herein.

[0199] In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C and r 2 As defined in the embodiments and categories and subclasses herein. In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C As defined in the embodiments, categories, and subclasses described herein.

[0200] In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C and r 2 As defined in the embodiments and categories and subclasses herein. In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C As defined in the embodiments, categories, and subclasses described herein.

[0201] In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C and r 2 As defined in the embodiments and categories and subclasses herein. In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C As defined in the embodiments, categories, and subclasses described herein.

[0202] In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C and r2 As defined in the embodiments and categories and subclasses herein. In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C As defined in the embodiments, categories, and subclasses described herein.

[0203] In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C and r 2 As defined in the embodiments and categories and subclasses herein. In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C As defined in the embodiments, categories, and subclasses described herein.

[0204] In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C and r 2 As defined in the embodiments and categories and subclasses herein. In some embodiments, R 2 (i.e. -L) 2 -R 2A Together) Where R 2C As defined in the embodiments, categories, and subclasses described herein.

[0205] In some embodiments, R 2 for

[0206] In some embodiments, R 2 for In some embodiments, R 2 for In some embodiments, R 2 for In some embodiments, R 2 for In some embodiments, R 2 for In some embodiments, R 2 for In some embodiments, R 2 for

[0207] In some embodiments, R 2 for In some embodiments, R 2 for In some embodiments, R 2 for In some embodiments, R 2 for In some embodiments, R 2 for In some embodiments, R 2 for

[0208] In some embodiments, R 2 for In some embodiments, R 2 for In some embodiments, R 2 for

[0209] In some embodiments, R 2 for In some embodiments, R 2 for In some embodiments, R 2 for In some embodiments, R 2 for In some embodiments, R 2 for In some embodiments, R 2 for

[0210] In some embodiments, R 2 The groups are selected from those described in the compounds in Table 1.

[0211] As generally defined above, R E Each instance is independently H or -L E -R EA ; or R E Two instances, together with their equivalent inserted atoms, form 3 to 8-membered saturated or partially unsaturated monocyclic rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 8 to 12-membered saturated or partially unsaturated bicyclic rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein each ring is R EEC Replace n instances.

[0212] In some embodiments, R E Each instance is independently H or -L E -R EAIn some embodiments, R E For H. In some embodiments, R E Each instance is independently -L E -R EA In some embodiments, R E Each instance is independently of R EA In some embodiments, R E Each instance is independently of R A In some embodiments, R E Each instance is independently of R EC r 3 Instances replace R B .

[0213] In some embodiments, R E Each instance is independently H or R EC r 3 Instances replace C 1-6 Aliphatic group. In some embodiments, R E Each instance is independently H or R EC r 3 Instances replace C 1-3 Aliphatic group. In some embodiments, R E Each instance is independently H or r of halogen. 3 Instances replace C 1-3 Aliphatic group. In some embodiments, R E Each instance is independently H or C. 1-3 Aliphatic group. In some embodiments, R E Each instance is independently H, -CH3, -CH2F, -CHF2-, or -CF3. In some embodiments, R E Each instance is independently H or -CH3.

[0214] In some embodiments, R E Each instance is independently of R EC r 3 Instances replace C 1-6 Aliphatic group. In some embodiments, R E Each instance is independently of R EC r 3 Instances replace C 1-3 Aliphatic C 1-3 In some embodiments, R E Each instance is independently of the halogenated r 3 Instances replace C 1-3 Aliphatic group. In some embodiments, R E Each instance is independently C 1-3Aliphatic group. In some embodiments, R E Each instance is independently -CH3, -CH2F, -CHF2-, or -CF3. In some embodiments, R E It is -CH3.

[0215] In some embodiments, R E Two instances, together with their equivalent inserted atoms, form 3 to 8-membered saturated or partially unsaturated monocyclic rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 8 to 12-membered saturated or partially unsaturated bicyclic rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein each ring is R EEC Replace n instances of R. In some embodiments, R E Two instances, together with their equivalent intercalating atoms, form 3- to 8-membered saturated or partially unsaturated monocyclic rings having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, and sulfur; wherein the ring is R EEC Replace n instances of R. In some embodiments, R E Two instances, together with their equivalent intercalating atoms, form 8- to 12-membered saturated or partially unsaturated bicyclic rings having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, and sulfur; wherein the rings are R EEC Replace n instances

[0216] In some embodiments, R E The groups are selected from those described in the compounds in Table 1.

[0217] As generally defined above, R Q -L Q -R QA Or R Q and R 1 Together with the inserted atoms, it forms a 4- to 8-membered saturated or partially unsaturated monocyclic ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 12-membered saturated or partially unsaturated bicyclic ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R Q1C p instances are replaced. In some embodiments, R Q -L Q -R QA In some embodiments, R Q -R QA .

[0218] In some embodiments, R Q and R 1 Together with the inserted atoms, it forms a 4- to 8-membered saturated or partially unsaturated monocyclic ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or an 8- to 12-membered saturated or partially unsaturated bicyclic ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R Q1Cp instances are replaced. In some embodiments, R Q and R 1 Together with the inserted atoms, they form a 4- to 8-membered saturated or partially unsaturated monocyclic ring having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, and sulfur; wherein the ring is R Q1C p instances are replaced. In some embodiments, R Q and R 1 Together with its intercalated atoms, it forms an 8- to 12-membered saturated or partially unsaturated bicyclic ring having 0 to 4 independently selected heteroatoms from nitrogen, oxygen, and sulfur; wherein the ring is R Q1C Replace p instances.

[0219] In some embodiments, R Q For 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.

[0220] In some embodiments, R Q Halogen, -CN, -OH, -O- (the substituted C is optional) 1-6 (Aliphatic group) or optionally substituted C 1-6 Aliphatic group. In some embodiments, R Q C is a halogen, -OH, or optionally substituted with 1 to 3 halogens. 1-3 Aliphatic group. In some embodiments, R Q It is fluorine, chlorine, -OH, or -CH3. In some embodiments, R Q For deuterium. In some embodiments, R Q The groups are selected from those described in the compounds in Table 1.

[0221] As generally defined above, R X -L X -R XA In some embodiments, R X -R XA In some embodiments, R XFor 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.

[0222] In some embodiments, R X Halogen, -CN, -OH, -O- (the substituted C is optional) 1-6 (Aliphatic group) or optionally substituted C 1-6 Aliphatic group. In some embodiments, R X Halogen, -OH, -O-(C 1-3 (Aliphatic group) or C 1-3 Aliphatic groups, in which each C 1-3 The aliphatic group is optionally replaced by one to three halogens. In some embodiments, R X It is fluorine, chlorine, -OCH3, or -CH3. In some embodiments, R X The groups are selected from those described in the compounds in Table 1.

[0223] As generally defined above, R Y -L Y -R YA Or R Y and R Z Together with its intercalated atoms, it forms a 4- to 7-membered partially unsaturated or aromatic ring having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, and sulfur; wherein the ring is R YZC q instances are replaced. In some embodiments, R Y -L Y -R YA In some embodiments, R Y and R Z Together with its intercalated atoms, it forms a 4- to 7-membered partially unsaturated or aromatic ring having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, and sulfur; wherein the ring is R YZC q instances are replaced. In some embodiments, R Y The groups are selected from those described in the compounds in Table 1.

[0224] As generally defined above, R Z -L Z -RZA Or R Y and R Z Together with its intercalated atoms, it forms a 4- to 7-membered partially unsaturated or aromatic ring having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, and sulfur; wherein the ring is R YZC q instances are replaced. In some embodiments, R Z -L Z -R ZA In some embodiments, R Y and R Z Together with its intercalated atoms, it forms a 4- to 7-membered partially unsaturated or aromatic ring having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, and sulfur; wherein the ring is R YZC q instances are replaced. In some embodiments, R Z The groups are selected from those described in the compounds in Table 1.

[0225] As generally defined above, L 1 For covalent bonds or C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 It is a covalent bond. In some embodiments, L 1 C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 C 1-4 Divalent saturated or unsaturated, straight-chain or branched hydrocarbon chains.

[0226] In some embodiments, L1 C 1-2 A divalent saturated or unsaturated hydrocarbon chain, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 C 1-2 A divalent saturated or unsaturated hydrocarbon chain, wherein one or both methylene units of the chain are optionally and independently substituted with: -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 C 1-2 Divalent saturated or unsaturated hydrocarbon chains. In some embodiments, L 1 The groups are selected from those described in the compounds in Table 1.

[0227] As generally defined above, L 2 For covalent bonds or C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 It is a covalent bond. In some embodiments, L 2 C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6Heterocyclic alkyl groups, -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 C 1-4 Divalent saturated or unsaturated, straight-chain or branched hydrocarbon chains.

[0228] In some embodiments, L 2 C 1-2 A divalent saturated or unsaturated hydrocarbon chain, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 C 1-2 A divalent saturated or unsaturated hydrocarbon chain, wherein one or both methylene units of the chain are optionally and independently substituted with: -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 C 1-2 Divalent saturated or unsaturated hydrocarbon chains.

[0229] In some embodiments, L 2 It is -N(R)C(O)- or -N(R)C(O)N(R)-. In some embodiments, L 2 It is -N(H)C(O)- or -N(H)C(O)N(H)-. In some embodiments, L 2 It is -N(R)C(O)-. In some embodiments, L 2 It is -N(H)C(O)-. In some embodiments, L 2 It is -N(R)C(O)N(R)-. In some embodiments, L 2 It is -N(H)C(O)N(H)-. In some embodiments, L 2 For -N(R)-. In some embodiments, L 2For -N(H)-. In some embodiments, L 2 It is a covalent bond. In some embodiments, L 2 The groups are selected from those described in the compounds in Table 1.

[0230] As generally defined above, L E For covalent bonds or C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 E It is a covalent bond. In some embodiments, L E C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 E C 1-4 Divalent saturated or unsaturated, straight-chain or branched hydrocarbon chains.

[0231] In some embodiments, L E C 1-2 A divalent saturated or unsaturated hydrocarbon chain, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6Heterocyclic alkyl groups, -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 E C 1-2 A divalent saturated or unsaturated hydrocarbon chain, wherein one or both methylene units of the chain are optionally and independently substituted with: -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 E C 1-2 Divalent saturated or unsaturated hydrocarbon chains. In some embodiments, L E The groups are selected from those described in the compounds in Table 1.

[0232] As generally defined above, L Q For covalent bonds or C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 It is a covalent bond. In some embodiments, L Q C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 C 1-4Divalent saturated or unsaturated, straight-chain or branched hydrocarbon chains.

[0233] In some embodiments, L Q C 1-2 A divalent saturated or unsaturated hydrocarbon chain, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 C 1-2 A divalent saturated or unsaturated hydrocarbon chain, wherein one or both methylene units of the chain are optionally and independently substituted with: -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 Q1 C 1-2 Divalent saturated or unsaturated hydrocarbon chains. In some embodiments, L Q The groups are selected from those described in the compounds in Table 1.

[0234] As generally defined above, L X For covalent bonds or C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 It is a covalent bond. In some embodiments, L X C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L)2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 C 1-4 Divalent saturated or unsaturated, straight-chain or branched hydrocarbon chains.

[0235] In some embodiments, L X C 1-2 A divalent saturated or unsaturated hydrocarbon chain, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 C 1-2 A divalent saturated or unsaturated hydrocarbon chain, wherein one or both methylene units of the chain are optionally and independently substituted with: -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 X C 1-2 Divalent saturated or unsaturated hydrocarbon chains. In some embodiments, L X The groups are selected from those described in the compounds in Table 1.

[0236] As generally defined above, L Y For covalent bonds or C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6Heterocyclic alkyl groups, -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 Y It is a covalent bond. In some embodiments, L Y C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 Y C 1-4 Divalent saturated or unsaturated, straight-chain or branched hydrocarbon chains.

[0237] In some embodiments, L Y C 1-2 A divalent saturated or unsaturated hydrocarbon chain, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 Y C 1-2 A divalent saturated or unsaturated hydrocarbon chain, wherein one or both methylene units of the chain are optionally and independently substituted with: -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 Y C 1-2 Divalent saturated or unsaturated hydrocarbon chains.

[0238] In some embodiments, L Y-C(H)2-, -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 Y -C(H)2-, -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 Y It is -C(H)2-, -N(R)-, -N(R)C(O)-, or -C(O)N(R)-. In some embodiments, L Y It is -C(H)2-, -N(H)-, -N(H)C(O)-, or -C(O)N(H)-. In some embodiments, L Y The groups are selected from those described in the compounds in Table 1.

[0239] As generally defined above, L Z For covalent bonds or C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 Z It is a covalent bond. In some embodiments, L Z C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chains, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6Heterocyclic alkyl groups, -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 Z C 1-4 Divalent saturated or unsaturated, straight-chain or branched hydrocarbon chains.

[0240] In some embodiments, L Z C 1-2 A divalent saturated or unsaturated hydrocarbon chain, wherein one or both methylene units of the chain are optionally and independently substituted with: -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 Z C 1-2 A divalent saturated or unsaturated hydrocarbon chain, wherein one or both methylene units of the chain are optionally and independently substituted with: -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 Z C 1-2 Divalent saturated or unsaturated hydrocarbon chains.

[0241] In some embodiments, L Z -C(H)2-, -CH(R) L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 Heterocyclic alkyl groups, -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 Z -C(H)2-, -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 Z It is -C(H)2-, -N(R)-, -N(R)C(O)-, or -C(O)N(R)-. In some embodiments, L Z It is -C(H)2-, -N(H)-, -N(H)C(O)-, or -C(O)N(H)-. In some embodiments, L Z The groups are selected from those described in the compounds in Table 1.

[0242] As generally defined above, R 1A For R 1C r 1 Instances replace R A Or R B In some embodiments, R 1A For R A In some embodiments, R 1A For R 1C r 1 Instances replace R B .

[0243] In some embodiments, R 1A It 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 carbide ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbide ring; 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; wherein R 1A R 1C r 1 Replace one instance.

[0244] In some embodiments, R 1A For R 1C r 1 One instance of substituted phenyl. In some embodiments, R 1A It is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 1A R 1C r 1 Each instance is replaced. In some embodiments, R 1A It is a phenyl group or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 1AR 1C r 1 Replace one instance.

[0245] In some embodiments, R 1A It 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; or a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic ring, wherein R 1A R 1C r 1 Replace one instance.

[0246] In some embodiments, R 1A r is independently selected from the following groups 1 Examples of substituted phenyl groups: oxoyl, 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 group. In some embodiments, R 1A It is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 1A r is independently selected from the following groups 1 Examples of substitutions: oxo group, 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 group. In some embodiments, R 1AIt is a phenyl group or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 1A r is independently selected from the following groups 1 Examples of substitutions: oxo group, 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 groups.

[0247] In some embodiments, R 1A For R 1C One to three instances of substituted phenyl groups. In some embodiments, R 1A For R 1C Two instances of substituted phenyl groups. In some embodiments, R 1A For R 1C One example of a substituted phenyl group.

[0248] In some embodiments, R 1A A phenyl group that is independently substituted with one to three of the following groups: halogen, -CN-, -O- (optionally the substituted C- group is substituted). 1-6 (Aliphatic group) and optionally substituted C 1-6 Aliphatic group. In some embodiments, R 1A A phenyl group that is independently substituted with one to three of the following groups: halogen and C group that is optionally substituted with one to three halogens. 1-3 Aliphatic group. In some embodiments, R 1A A phenyl group that is substituted by one to three instances of groups independently selected from the following groups: fluorine, chlorine, -CH3, -CHF2 and -CF3.

[0249] In some embodiments, R 1A A phenyl group that is independently substituted with two of the following groups: halogen, -CN-, -O- (optionally the substituted C- group is substituted). 1-6 (Aliphatic group) and optionally substituted C 1-6 Aliphatic group. In some embodiments, R 1AA phenyl group that is independently substituted with two of the following groups: a halogen and a C group optionally substituted with one to three halogens. 1-3 Aliphatic group. In some embodiments, R 1A A phenyl group that is substituted by two instances of groups independently selected from the following: fluorine, chlorine, -CH3, -CHF2, and -CF3.

[0250] In some embodiments, R 1A A phenyl group substituted with one of the following groups: halogen, -CN-, -O- (optionally the substituted C 1-6 (Aliphatic group) and optionally substituted C 1-6 Aliphatic group. In some embodiments, R 1A The phenyl group is substituted with one halogen or C substituted with one to three halogens. 1-3 Aliphatic group. In some embodiments, R 1A It is a phenyl group substituted with one fluorine, chlorine, -CH3, -CHF2 or -CF3.

[0251] In some embodiments, R 1A for Where R 1C and r 1 As defined in the embodiments and categories and subclasses herein. In some embodiments, R 1A for Where R 1C As defined in the embodiments and categories and subclasses herein. In some embodiments, R 1A for Where R 1C As defined in the embodiments and categories and subclasses herein. In some embodiments, R 1A for Where R 1C As defined in the embodiments and categories and subclasses herein. In some embodiments, R 1A for Where R 1C As defined in the embodiments, categories, and subclasses described herein.

[0252] In some embodiments, R 1A for Where R 1C Each instance is independently a halogen, -CN, -O- (optionally substituted C). 1-6 (Aliphatic group) or optionally substituted C 1-6 Aliphatic group. In some embodiments, R 1A for Where R 1C Each instance is independently a halogen or optionally a C substituted with one to three halogens.1-3 Aliphatic group. In some embodiments, R 1A for Where R 1C Each instance is independently a halogen or optionally a C substituted with one to three halogens. 1-3 Aliphatic group. In some embodiments, R 1A for Where R 1C Each instance is independently a halogen or optionally a C substituted with one to three halogens. 1-3 Aliphatic group. In some embodiments, R 1A for Where R 1C Each instance is independently fluorine, chlorine, -CH3, -CHF2, or -CF3. In some embodiments, R 1A for Where R 1C C is a halogen or optionally substituted with 1 to 3 halogens. 1-3 Aliphatic groups.

[0253] In some embodiments, R 1A for In some embodiments, R 1A for

[0254] In some embodiments, R 1A for Where R 1C and r 1 As defined in the embodiments and categories and subclasses herein. In some embodiments, R 1A for In some embodiments, R 1A for In some embodiments, R 1A for

[0255] In some embodiments, R 1A For 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, -O C(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.

[0256] In some embodiments, R 1A For 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.

[0257] In some embodiments, R 1A For oxidation. In some embodiments, R... 1A It is a halogen. In some embodiments, R 1A For -CN. In some embodiments, R 1A For -NO2. In some embodiments, R 1A For -OR. In some embodiments, R 1A For -SR. In some embodiments, R 1A For -NR2. In some embodiments, R 1A For -S(O)2R. In some embodiments, R 1A It is -S(O)2NR2. In some embodiments, R 1A For -S(O)2F. In some embodiments, R 1A For -S(O)R. In some embodiments, R 1A For -S(O)NR2. In some embodiments, R 1A For -S(O)(NR)R. In some embodiments, R 1A For -C(O)R. In some embodiments, R 1A For -C(O)OR. In some embodiments, R 1A For -C(O)NR2. In some embodiments, R 1A For -C(O)N(R)OR. In some embodiments, R 1A For -OC(O)R. In some embodiments, R 1A For -OC(O)NR2. In some embodiments, R 1A It is -N(R)C(O)OR. In some embodiments, R 1A It is -N(R)C(O)R. In some embodiments, R 1A It is -N(R)C(O)NR2. In some embodiments, R 1AFor example, -N(R)C(NR)NR2. In some embodiments, R 1A It is -N(R)S(O)2NR2. In some embodiments, R 1A It is -N(R)S(O)2R. In some embodiments, R 1A For -P(O)R2. In some embodiments, R 1A For -P(O)(R)OR. In some embodiments, R 1A =-B(OR)2. In some embodiments, R 1A It is deuterium.

[0258] In some embodiments, R 1A For 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.

[0259] In some embodiments, R 1A It is a halogen, -CN, or -NO2. In some embodiments, R 1A For -OR, -SR, or -NR2. In some embodiments, R 1A It can be -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 It can be -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, R 1A For -OC(O)R or -OC(O)NR2. In some embodiments, R 1A It can be -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 It is either -P(O)R2 or -P(O)(R)OR.

[0260] In some embodiments, R 1A For -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R 1AIt can be -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.

[0261] In some embodiments, R 1A It is -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R 1A It is -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 1A It can be -SR, -S(O)2R, or -S(O)R. In some embodiments, R 1A It is -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 1A It is -S(O)2NR2 or -S(O)NR2. In some embodiments, R 1A It can be -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0262] In some embodiments, R 1A It is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R 1A It is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R 1A It is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R 1A It is -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R 1A It is -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0263] In some embodiments, R 1A For -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R 1A It can be -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R 1A It is -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0264] In some embodiments, R 1A C 1-6 Aliphatic chain; phenyl; naphthyl; 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 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 R 1C r 1 Replace one instance.

[0265] In some embodiments, R 1A For R 1C r 1 Instances replace C 1-6 Aliphatic group. In some embodiments, R 1A For R 1C r 1 One instance of substituted phenyl. In some embodiments, R 1A For R 1C r 1 One instance of naphthyl substitution. In some embodiments, R 1A It 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 R 1C r 1 Each instance is replaced. In some embodiments, R 1A It is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R 1C r 1 Each instance is replaced. In some embodiments, R 1A For R 1C r 1 Each instance replaces a 3- to 7-member saturated or partially unsaturated monocyclic carbon ring. In some embodiments, R 1A For R 1C r 1 Each instance replaces a 5- to 12-member saturated or partially unsaturated bicyclic carbon ring. In some embodiments, R 1A It is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R 1C r 1 Each instance is replaced. In some embodiments, R 1AIt 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 the ring is R 1C r 1 Replace one instance.

[0266] In some embodiments, R 1A It 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 1C r 1 Each instance is replaced. In some embodiments, R 1A It is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; 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 R 1C r 1 Replace one instance.

[0267] In some embodiments, R 1A It is phenyl; naphthyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring or a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; each of which is R 1C r 1 Each instance is replaced. In some embodiments, R 1A It 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 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 R 1C r 1 Replace one instance.

[0268] In some embodiments, R 1A It is a phenyl group; 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R 1C r 1 Each instance is replaced. In some embodiments, R 1AIt is a naphthyl group; 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R 1C r 1 Replace one instance.

[0269] In some embodiments, R 1A It is phenyl or naphthyl; each of them is R 1C r 1 Each instance is replaced. In some embodiments, R 1A It 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 R 1C r 1 Each instance is replaced. In some embodiments, R 1A It consists of 3 to 7 saturated or partially unsaturated monocyclic carbon rings or 5 to 12 saturated or partially unsaturated bicyclic carbon rings; each is respectively bound by R 1C r 1 Each instance is replaced. In some embodiments, R 1A It 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 R 1C r 1 Replace one instance.

[0270] In some embodiments, R 1A It is a phenyl group 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 1C r 1 Each instance is replaced. In some embodiments, R 1A It is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 independent heteroatoms selected from nitrogen, oxygen, and sulfur; each of which is R 1C r 1 Each instance is replaced. In some embodiments, R 1A It is a naphthyl group 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 1C r 1 Each instance is replaced. In some embodiments, R 1AIt is a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring 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 R 1C r 1 Replace one instance.

[0271] In some embodiments, R 1A It is a phenyl or a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring, each of which is bonded by R 1C r 1 Each instance is replaced. In some embodiments, R 1A It is a naphthyl or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; each of them is R 1C r 1 Each instance is replaced. In some embodiments, R 1A It 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R 1C r 1 Each instance is replaced. In some embodiments, R 1A It 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R 1C r 1 Replace one instance.

[0272] In some embodiments, R 1A C 1-6 Aliphatic chains; 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings; 5- to 12-membered saturated or partially unsaturated bicyclic carbon rings; 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 7- to 12-membered saturated or partially unsaturated bicyclic heterocycles having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R 1C r 1 Each instance is replaced. In some embodiments, R 1A C 1-6 Aliphatic chain; phenyl; naphthyl; 3 to 7 membered saturated or partially unsaturated monocyclic carbon rings or 5 to 12 membered saturated or partially unsaturated bicyclic carbon rings; each of which is R 1C r 1 Each instance is replaced. In some embodiments, R 1A C 1-6Aliphatic 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R 1C r 1 Replace one instance.

[0273] In some embodiments, R 1A C 1-6 Aliphatic chains, 3 to 7-membered saturated or partially unsaturated monocyclic carbon rings, or 5 to 12-membered saturated or partially unsaturated bicyclic carbon rings; each is respectively bound by R 1C r 1 Each instance is replaced. In some embodiments, R 1A C 1-6 Aliphatic chains, 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings, or 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 independent heteroatoms selected from nitrogen, oxygen, and sulfur; each of which is R 1C r 1 Each instance is replaced. In some embodiments, R 1A C 1-6 Aliphatic chains, phenyl groups, or 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings, each of which is R 1C r 1 Replace one instance.

[0274] In some embodiments, R 1A The groups are selected from those described in the compounds in Table 1.

[0275] As generally defined above, R 2A For R 2C r 2 Instances replace R A or R B In some embodiments, R 2A For R A In some embodiments, R 2A For R 2C r 2 Instances replace R B .

[0276] In some embodiments, R 2AIt is phenyl; naphthyl; cubic; 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 carbide ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbide ring; 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; wherein R 2A R 2C r 2 Replace one instance.

[0277] In some embodiments, R 2A It 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R 2A R 2C r 2 Each instance is replaced. In some embodiments, R 2A It is a phenyl group; having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur in an 8- to 10-membered bicyclic heteroaryl ring; or having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur in a 7- to 12-membered saturated or partially unsaturated bicyclic heterocycle; wherein R 2A R 2C r 2 Each instance is replaced. In some embodiments, R 2A It is a phenyl group or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R 2A R 2C r 2 Replace one instance.

[0278] In some embodiments, R 2A It 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R 2A r is independently selected from the following groups 2Examples of substitutions: oxo group, 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 group. In some embodiments, R 2A It is a phenyl group; having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur in an 8- to 10-membered bicyclic heteroaryl ring; or having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur in a 7- to 12-membered saturated or partially unsaturated bicyclic heterocycle; wherein R 2A r is independently selected from the following groups 2 Examples of substitutions: oxo group, 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 group. In some embodiments, R 2A It is a phenyl group or an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R 2A r is independently selected from the following groups 2Examples of substitutions: oxo group, 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 groups.

[0279] In some embodiments, R 2A For R 2C r 2 One instance of substituted phenyl. In some embodiments, R 2A r is independently selected from the following groups 2 Examples of substituted phenyl groups: oxoyl, 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 groups.

[0280] In some embodiments, R 2A A phenyl group that is independently substituted with one to three of the following groups: halogen, -CN-, -O- (optionally the substituted C- group is substituted). 1-6 (Aliphatic group) and optionally substituted C 1-6 Aliphatic group. In some embodiments, R 2A A phenyl group that is independently substituted with one to three of the following groups: halogen and C group that is optionally substituted with one to three halogens. 1-3 Aliphatic group. In some embodiments, R 2A A phenyl group that is substituted by one to three instances of groups independently selected from the following groups: fluorine, chlorine, -CH3, -CHF2 and -CF3.

[0281] In some embodiments, R2A A phenyl group that is independently substituted with two of the following groups: halogen, -CN-, -O- (optionally the substituted C- group is substituted). 1-6 (Aliphatic group) and optionally substituted C 1-6 Aliphatic group. In some embodiments, R 2A A phenyl group that is independently substituted with two of the following groups: a halogen and a C group optionally substituted with one to three halogens. 1-3 Aliphatic group. In some embodiments, R 2A A phenyl group that is substituted by two instances of groups independently selected from the following: fluorine, chlorine, -CH3, -CHF2, and -CF3.

[0282] In some embodiments, R 2A It is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R 2A R 2C r 2 Each instance is replaced. In some embodiments, R 2A It is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R 2A r is independently selected from the following groups 2 Examples of substitutions: oxo group, 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 groups.

[0283] In some embodiments, R 2A It is an 8- to 10-membered bicyclic heteroaryl ring having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R 2A R 2C r 2 Each instance is replaced. In some embodiments, R 2A It is an 8- to 10-membered bicyclic heteroaryl ring having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R 2A r is independently selected from the following groups 2Examples of substitutions: oxo group, 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 Aliphatic groups.

[0284] In some embodiments, R 2A It is an 8- to 10-membered bicyclic heteroaryl ring having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R 2A It is substituted by 0 to 2 instances of a group independently selected from the following: halogen, -CN-, -O- (optionally the substituted C 1-6 (Aliphatic group) and optionally substituted C 1-6 Aliphatic group. In some embodiments, R 2A It is an 8- to 10-membered bicyclic heteroaryl ring having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R 2A The group is substituted by 0 to 2 instances of groups independently selected from the following: halogens and C groups optionally substituted by 1 to 3 halogens. 1-3 Aliphatic group. In some embodiments, R 2A It is an 8- to 10-membered bicyclic heteroaryl ring having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R 2A It may be substituted by 0 to 2 instances of groups independently selected from the following: fluorine, chlorine, -CH3, -CHF2 and -CF3.

[0285] In some embodiments, R 2A for Where R 2C and r 2 As defined in the embodiments and categories and subclasses herein. In some embodiments, R 2A for In some embodiments, R 2A for In some embodiments, R 2A for In some embodiments, R 2A for In some embodiments, R 2A for In some embodiments, R 2A for In some embodiments, R 2A for In some embodiments, R 2A for In some embodiments, R 2A for In some embodiments, R 2A for In some embodiments, R 2A for

[0286] In some embodiments, R 2A For 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, -O C(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.

[0287] In some embodiments, R 2A For 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.

[0288] In some embodiments, R 2A For oxidation. In some embodiments, R... 2A It is a halogen. In some embodiments, R 2A For -CN. In some embodiments, R 2A For -NO2. In some embodiments, R 2A For -OR. In some embodiments, R 2A For -SR. In some embodiments, R2A For -NR2. In some embodiments, R 2A For -S(O)2R. In some embodiments, R 2A It is -S(O)2NR2. In some embodiments, R 2A It is -S(O)2F. In some embodiments, R 2A For -S(O)R. In some embodiments, R 2A For -S(O)NR2. In some embodiments, R 2A For -S(O)(NR)R. In some embodiments, R 2A For -C(O)R. In some embodiments, R 2A For -C(O)OR. In some embodiments, R 2A For -C(O)NR2. In some embodiments, R 2A For -C(O)N(R)OR. In some embodiments, R 2A For -OC(O)R. In some embodiments, R 2A For -OC(O)NR2. In some embodiments, R 2A It is -N(R)C(O)OR. In some embodiments, R 2A It is -N(R)C(O)R. In some embodiments, R 2A It is -N(R)C(O)NR2. In some embodiments, R 2A For example, -N(R)C(NR)NR2. In some embodiments, R 2A It is -N(R)S(O)2NR2. In some embodiments, R 2A It is -N(R)S(O)2R. In some embodiments, R 2A For -P(O)R2. In some embodiments, R 2A For -P(O)(R)OR. In some embodiments, R 2A =-B(OR)2. In some embodiments, R 2A It is deuterium.

[0289] In some embodiments, R 2AFor 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.

[0290] In some embodiments, R 2A It is a halogen, -CN, or -NO2. In some embodiments, R 2A For -OR, -SR, or -NR2. In some embodiments, R 2A It can be -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 It can be -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, R 2A For -OC(O)R or -OC(O)NR2. In some embodiments, R 2A It can be -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 It is either -P(O)R2 or -P(O)(R)OR.

[0291] In some embodiments, R 2A For -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R 2A It can be -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.

[0292] In some embodiments, R 2A It is -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R 2AIt is -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 2A It can be -SR, -S(O)2R, or -S(O)R. In some embodiments, R 2A It is -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 2A It is -S(O)2NR2 or -S(O)NR2. In some embodiments, R 2A It can be -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0293] In some embodiments, R 2A It is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R 2A It is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R 2A It is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R 2A It is -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R 2A It is -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0294] In some embodiments, R 2A For -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R 2A It can be -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R 2A It is -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0295] In some embodiments, R 2A C 1-6 Aliphatic chain; phenyl; naphthyl; cubic; 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 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 R 2C r2 Replace one instance.

[0296] In some embodiments, R 2A For R 2C r 2 Instances replace C 1-6 Aliphatic group. In some embodiments, R 2A For R 2C r 2 One instance of substituted phenyl. In some embodiments, R 2A For R 2C r 2 One instance of naphthyl substitution. In some embodiments, R 2A For R 2C r 2 One instance of substituted cubic alkyl group. In some embodiments, R 2A For R 2C r 2 One instance of substituted adamantyl alkyl group. In some embodiments, R 2A It 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 R 2C r 2 Each instance is replaced. In some embodiments, R 2A It is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R 2C r 2 Each instance is replaced. In some embodiments, R 2A For R 2C r 2 Each instance replaces a 3- to 7-member saturated or partially unsaturated monocyclic carbon ring. In some embodiments, R 2A For R 2C r 2 Each instance replaces a 5- to 12-member saturated or partially unsaturated bicyclic carbon ring. In some embodiments, R 2A It is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R 2C r 2 Each instance is replaced. In some embodiments, R 2A It 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 the ring is R 2C r 2 Replace one instance.

[0297] In some embodiments, R 2AIt 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 2C r 2 Each instance is replaced. In some embodiments, R 2A It is a cubic alkyl group; an adamantyl alkyl group; a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; 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 R 2C r 2 Replace one instance.

[0298] In some embodiments, R 2A It is phenyl; naphthyl; cubic; adamantyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbide ring or a 5- to 12-membered saturated or partially unsaturated bicyclic carbide ring; each of which is R 2C r 2 Each instance is replaced. In some embodiments, R 2A It 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 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 R 2C r 2 Replace one instance.

[0299] In some embodiments, R 2A It is a phenyl group; 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R 2C r 2 Each instance is replaced. In some embodiments, R 2A It is naphthyl; cubic; 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R 2C r 2 Replace one instance.

[0300] In some embodiments, R 2A It is phenyl or naphthyl; each of them is R 2C r 2 Each instance is replaced. In some embodiments, R 2A It 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 R 2C r 2 Each instance is replaced. In some embodiments, R 2A It consists of 3 to 7 saturated or partially unsaturated monocyclic carbon rings or 5 to 12 saturated or partially unsaturated bicyclic carbon rings; each is respectively bound by R 2C r 2 Each instance is replaced. In some embodiments, R 2A It 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 R 2C r 2 Replace one instance.

[0301] In some embodiments, R 2A It is a phenyl group 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 2C r 2 Each instance is replaced. In some embodiments, R 2A It is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 independent heteroatoms selected from nitrogen, oxygen, and sulfur; each of which is R 2C r 2 Each instance is replaced. In some embodiments, R 2A It is a naphthyl group 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 2C r 2 Each instance is replaced. In some embodiments, R 2A It is a cubic alkyl group; an adamantyl alkyl group; a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; 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 R 2C r 2 Replace one instance.

[0302] In some embodiments, R 2A It is a phenyl or a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring; each of them is R 2C r2 Each instance is replaced. In some embodiments, R 2A It is naphthyl; cubic; adamantyl; or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; each of which is R 2C r 2 Each instance is replaced. In some embodiments, R 2A It 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R 2C r 2 Each instance is replaced. In some embodiments, R 2A It 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R 2C r 2 Replace one instance.

[0303] In some embodiments, R 2A C 1-6 Aliphatic chain; cubic alkyl; adamantyl; 3 to 7 membered saturated or partially unsaturated monocyclic carbon ring; 5 to 12 membered saturated or partially unsaturated bicyclic carbon ring; 3 to 7 membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 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 R 2C r 2 Each instance is replaced. In some embodiments, R 2A C 1-6 Aliphatic chain; phenyl; naphthyl; cubic; adamantyl; 3 to 7 member saturated or partially unsaturated monocyclic carbocyclic rings or 5 to 12 member saturated or partially unsaturated bicyclic carbocyclic rings; each of which is R 2C r 2 Each instance is replaced. In some embodiments, R 2A 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R 2C r 2 Replace one instance.

[0304] In some embodiments, R 2A C 1-6Aliphatic chains, cubic alkyl, adamantyl, 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings or 5- to 12-membered saturated or partially unsaturated bicyclic carbon rings; each is respectively bound by R 2C r 2 Each instance is replaced. In some embodiments, R 2A C 1-6 Aliphatic chains, 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings, or 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 independent heteroatoms selected from nitrogen, oxygen, and sulfur; each of which is R 2C r 2 Each instance is replaced. In some embodiments, R 2A C 1-6 Aliphatic chains, phenyl groups, or 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings, each of which is R 2C r 2 Replace one instance.

[0305] In some embodiments, R 2A The groups are selected from those described in the compounds in Table 1.

[0306] As generally defined above, R EA For R EC r 3 Instances replace R A or R B In some embodiments, R EA For R A In some embodiments, R EA For R EC r 3 Instances replace R B .

[0307] In some embodiments, R EA Each instance is independently of R EC r 3 Instances replace C 1-6 Aliphatic group. In some embodiments, R EA Each instance is independently of R EC r 3 Instances replace C 1-3 Aliphatic group. In some embodiments, R EA Each instance is independently of the halogenated r 3 Instances replace C 1-3 Aliphatic group. In some embodiments, R EA Each instance is independently C 1-3 Aliphatic group. In some embodiments, R E Each instance is independently -CH3, -CH2F, -CHF2-, or -CF3. In some embodiments, REA It is -CH3.

[0308] In some embodiments, R EA The groups are selected from those described in the compounds in Table 1.

[0309] As generally defined above, R QA For R QC r 4 Instances replace R A or R B In some embodiments, R QA For R A In some embodiments, R QA For R QC r 4 Instances replace R B .

[0310] In some embodiments, R QA For 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, -O C(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.

[0311] In some embodiments, R QA For 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.

[0312] In some embodiments, R QA For oxidation. In some embodiments, R... QA It is a halogen. In some embodiments, R QA For -CN. In some embodiments, RQA For -NO2. In some embodiments, R QA For -OR. In some embodiments, R QA For -SR. In some embodiments, R QA For -NR2. In some embodiments, R QA For -S(O)2R. In some embodiments, R QA It is -S(O)2NR2. In some embodiments, R QA It is -S(O)2F. In some embodiments, R QA For -S(O)R. In some embodiments, R QA For -S(O)NR2. In some embodiments, R QA For -S(O)(NR)R. In some embodiments, R QA For -C(O)R. In some embodiments, R QA For -C(O)OR. In some embodiments, R QA For -C(O)NR2. In some embodiments, R QA For -C(O)N(R)OR. In some embodiments, R QA For -OC(O)R. In some embodiments, R QA For -OC(O)NR2. In some embodiments, R QA It is -N(R)C(O)OR. In some embodiments, R QA It is -N(R)C(O)R. In some embodiments, R QA It is -N(R)C(O)NR2. In some embodiments, R QA For example, -N(R)C(NR)NR2. In some embodiments, R QA It is -N(R)S(O)2NR2. In some embodiments, R QA It is -N(R)S(O)2R. In some embodiments, R QA For -P(O)R2. In some embodiments, R QA For -P(O)(R)OR. In some embodiments, R QA =-B(OR)2. In some embodiments, R QA It is deuterium.

[0313] In some embodiments, R QAFor 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.

[0314] In some embodiments, R QA It is a halogen, -CN, or -NO2. In some embodiments, R QA For -OR, -SR, or -NR2. In some embodiments, R QA It can be -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R QA It can be -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, R QA For -OC(O)R or -OC(O)NR2. In some embodiments, R QA It can be -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 QA It is either -P(O)R2 or -P(O)(R)OR.

[0315] In some embodiments, R QA For -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R QA It can be -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 QA 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.

[0316] In some embodiments, R QA It is -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R QAIt is -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R QA It can be -SR, -S(O)2R, or -S(O)R. In some embodiments, R QA It is -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R QA It is -S(O)2NR2 or -S(O)NR2. In some embodiments, R QA It can be -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0317] In some embodiments, R QA It is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R QA It is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R QA It is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R QA It is -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R QA It is -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0318] In some embodiments, R QA For -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R QA It can be -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R QA It is -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0319] In some embodiments, R QA C 1-6 Aliphatic chain; phenyl; naphthyl; 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 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 R QC r 6 Replace one instance.

[0320] In some embodiments, R QA For R QC r 4 Instances replace C 1-6 Aliphatic group. In some embodiments, R QA For R QC r 4 One instance of substituted phenyl. In some embodiments, R QA For R QC r 4 One instance of naphthyl substitution. In some embodiments, R QA It 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 R QC r 4 Each instance is replaced. In some embodiments, R QA It is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R QC r 4 Each instance is replaced. In some embodiments, R QA For R QC r 4 Each instance replaces a 3- to 7-member saturated or partially unsaturated monocyclic carbon ring. In some embodiments, R QA For R QC r 4 Each instance replaces a 5- to 12-member saturated or partially unsaturated bicyclic carbon ring. In some embodiments, R QA It is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R QC r 4 Each instance is replaced. In some embodiments, R QA It 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 the ring is R QC r 4 Replace one instance.

[0321] In some embodiments, R QAIt 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 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 R QC r 4 Replace one instance.

[0322] In some embodiments, R QA It 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 QC r 4 Each instance is replaced. In some embodiments, R QA It is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; 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 R QC r 4 Replace one instance.

[0323] In some embodiments, R QA It is phenyl; naphthyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring or a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; each of which is R QC r 4 Each instance is replaced. In some embodiments, R QA It 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 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 R QC r 4 Replace one instance.

[0324] In some embodiments, R QAIt is a phenyl group; 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R QC r 4 Each instance is replaced. In some embodiments, R QA It is a naphthyl group; 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R QC r 4 Replace one instance.

[0325] In some embodiments, R QA It is phenyl or naphthyl; each of them is R QC r 4 Each instance is replaced. In some embodiments, R QA It 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 R QC r 4 Each instance is replaced. In some embodiments, R QA It consists of 3 to 7 saturated or partially unsaturated monocyclic carbon rings or 5 to 12 saturated or partially unsaturated bicyclic carbon rings; each is respectively bound by R QC r 4 Each instance is replaced. In some embodiments, R QA It 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 R QC r 4 Replace one instance.

[0326] In some embodiments, R QA It is a phenyl group 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 QC r 4 Each instance is replaced. In some embodiments, R QA It is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 independent heteroatoms selected from nitrogen, oxygen, and sulfur; each of which is R QC r 4 Each instance is replaced. In some embodiments, RQA It is a naphthyl group 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 QC r 4 Each instance is replaced. In some embodiments, R QA It is a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring 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 R QC r 4 Replace one instance.

[0327] In some embodiments, R QA It is a phenyl or a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring; each of them is R QC r 4 Each instance is replaced. In some embodiments, R QA It is a naphthyl or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; each of them is R QC r 4 Each instance is replaced. In some embodiments, R QA It 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R QC r 4 Each instance is replaced. In some embodiments, R QA It 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R QC r 4 Replace one instance.

[0328] In some embodiments, R QA C 1-6 Aliphatic chains; 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings; 5- to 12-membered saturated or partially unsaturated bicyclic carbon rings; 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 7- to 12-membered saturated or partially unsaturated bicyclic heterocycles having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R QC r 4 Each instance is replaced. In some embodiments, R QA C 1-6 Aliphatic chain; phenyl; naphthyl; 3 to 7 membered saturated or partially unsaturated monocyclic carbon rings or 5 to 12 membered saturated or partially unsaturated bicyclic carbon rings; each of which is R QC r 4Each instance is replaced. In some embodiments, R QA 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R QC r 4 Replace one instance.

[0329] In some embodiments, R QA C 1-6 Aliphatic chains, 3 to 7-membered saturated or partially unsaturated monocyclic carbon rings, or 5 to 12-membered saturated or partially unsaturated bicyclic carbon rings; each is respectively bound by R QC r 4 Each instance is replaced. In some embodiments, R QA C 1-6 Aliphatic chains, 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings, or 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 independent heteroatoms selected from nitrogen, oxygen, and sulfur; each of which is R QC r 4 Each instance is replaced. In some embodiments, R QA C 1-6 Aliphatic chains, phenyl groups, or 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings; each of which is R QC r 4 Replace one instance.

[0330] In some embodiments, R QA The groups are selected from those described in the compounds in Table 1.

[0331] As generally defined above, R XA For R XC r 5 Instances replace R A or R B In some embodiments, R XA For R A In some embodiments, R XA For R XC r 5 Instances replace R B .

[0332] In some embodiments, R XAFor 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, -O C(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.

[0333] In some embodiments, R XA For 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.

[0334] In some embodiments, R XA For oxidation. In some embodiments, R... XA It is a halogen. In some embodiments, R XA For -CN. In some embodiments, R XA For -NO2. In some embodiments, R XA For -OR. In some embodiments, R XA For -SR. In some embodiments, R XA For -NR2. In some embodiments, R XA For -S(O)2R. In some embodiments, R XA It is -S(O)2NR2. In some embodiments, R XA It is -S(O)2F. In some embodiments, R XA For -S(O)R. In some embodiments, R XA For -S(O)NR2. In some embodiments, R XA For -S(O)(NR)R. In some embodiments, R XA For -C(O)R. In some embodiments, R XAFor -C(O)OR. In some embodiments, R XA For -C(O)NR2. In some embodiments, R XA For -C(O)N(R)OR. In some embodiments, R XA For -OC(O)R. In some embodiments, R XA For -OC(O)NR2. In some embodiments, R XA It is -N(R)C(O)OR. In some embodiments, R XA It is -N(R)C(O)R. In some embodiments, R XA It is -N(R)C(O)NR2. In some embodiments, R XA For example, -N(R)C(NR)NR2. In some embodiments, R XA It is -N(R)S(O)2NR2. In some embodiments, R XA It is -N(R)S(O)2R. In some embodiments, R XA For -P(O)R2. In some embodiments, R XA For -P(O)(R)OR. In some embodiments, R XA =-B(OR)2. In some embodiments, R XA It is deuterium.

[0335] In some embodiments, R XA For 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.

[0336] In some embodiments, R XA It is a halogen, -CN, or -NO2. In some embodiments, R XA For -OR, -SR, or -NR2. In some embodiments, R XA It can be -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R XA It can be -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, RXA For -OC(O)R or -OC(O)NR2. In some embodiments, R XA It can be -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 XA It is either -P(O)R2 or -P(O)(R)OR.

[0337] In some embodiments, R XA For -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R XA It can be -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 XA 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.

[0338] In some embodiments, R XA It is -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R XA It is -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R XA It can be -SR, -S(O)2R, or -S(O)R. In some embodiments, R XA It is -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R XA It is -S(O)2NR2 or -S(O)NR2. In some embodiments, R XA It can be -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0339] In some embodiments, R XA It is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R XA It is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R XA It is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R XA It is -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R XAIt is -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0340] In some embodiments, R XA For -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R XA It can be -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R XA It is -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0341] In some embodiments, R XA C 1-6 Aliphatic chain; phenyl; naphthyl; 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 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 R XC r 5 Replace one instance.

[0342] In some embodiments, R XA For R XC r 5 Instances replace C 1-6 Aliphatic group. In some embodiments, R XA For R XC r 5 One instance of substituted phenyl. In some embodiments, R XA For R XC r 5 One instance of naphthyl substitution. In some embodiments, R XA It 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 R XC r 5 Each instance is replaced. In some embodiments, R XA It is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R XC r 5 Each instance is replaced. In some embodiments, R XA For R XC r5 Each instance replaces a 3- to 7-member saturated or partially unsaturated monocyclic carbon ring. In some embodiments, R XA For R XC r 5 Each instance replaces a 5- to 12-member saturated or partially unsaturated bicyclic carbon ring. In some embodiments, R XA It is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R XC r 5 Each instance is replaced. In some embodiments, R XA It 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 the ring is R XC r 5 Replace one instance.

[0343] In some embodiments, R XA It 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 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 R XC r 5 Replace one instance.

[0344] In some embodiments, R XA It 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 XC r 5 Each instance is replaced. In some embodiments, R XA It is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; 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 R XC r 5 Replace one instance.

[0345] In some embodiments, R XAIt is phenyl; naphthyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring or a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; each of which is R XC r 5 Each instance is replaced. In some embodiments, R XA It 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 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 R XC r 5 Replace one instance.

[0346] In some embodiments, R XA It is a phenyl group; 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R XC r 5 Each instance is replaced. In some embodiments, R XA It is a naphthyl group; 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R XC r 5 Replace one instance.

[0347] In some embodiments, R XA It is phenyl or naphthyl; each of them is R XC r 5 Each instance is replaced. In some embodiments, R XA It 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 R XC r 5 Each instance is replaced. In some embodiments, R XA It consists of 3 to 7 saturated or partially unsaturated monocyclic carbon rings or 5 to 12 saturated or partially unsaturated bicyclic carbon rings; each is respectively bound by R XC r 5 Each instance is replaced. In some embodiments, R XAIt 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 R XC r 5 Replace one instance.

[0348] In some embodiments, R XA It is a phenyl group 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 XC r 5 Each instance is replaced. In some embodiments, R XA It is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 independent heteroatoms selected from nitrogen, oxygen, and sulfur; each of which is R XC r 5 Each instance is replaced. In some embodiments, R XA It is a naphthyl group 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 XC r 5 Each instance is replaced. In some embodiments, R XA It is a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring 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 R XC r 5 Replace one instance.

[0349] In some embodiments, R XA It is a phenyl or a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring, each of which is bonded by R XC r 5 Each instance is replaced. In some embodiments, R XA It is a naphthyl or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; each of them is R XC r 5 Each instance is replaced. In some embodiments, R XA It 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R XC r 5 Each instance is replaced. In some embodiments, R XA It 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is RXC r 5 Replace one instance.

[0350] In some embodiments, R XA C 1-6 Aliphatic chains; 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings; 5- to 12-membered saturated or partially unsaturated bicyclic carbon rings; 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 7- to 12-membered saturated or partially unsaturated bicyclic heterocycles having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R XC r 5 Each instance is replaced. In some embodiments, R XA C 1-6 Aliphatic chain; phenyl; naphthyl; 3 to 7 membered saturated or partially unsaturated monocyclic carbon rings or 5 to 12 membered saturated or partially unsaturated bicyclic carbon rings; each of which is R XC r 5 Each instance is replaced. In some embodiments, R XA 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R XC r 5 Replace one instance.

[0351] In some embodiments, R XA C 1-6 Aliphatic chains, 3 to 7-membered saturated or partially unsaturated monocyclic carbon rings, or 5 to 12-membered saturated or partially unsaturated bicyclic carbon rings; each is respectively bound by R XC r 5 Each instance is replaced. In some embodiments, R XA C 1-6 Aliphatic chains, 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings, or 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 independent heteroatoms selected from nitrogen, oxygen, and sulfur; each of which is R XC r 5 Each instance is replaced. In some embodiments, R XA C 1-6 Aliphatic chains, phenyl groups, or 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings; each of which is R XC r 5 Replace one instance.

[0352] In some embodiments, R XA The groups are selected from those described in the compounds in Table 1.

[0353] As generally described above, R YA For R YC r 6 Instances replace R A or R B In some embodiments, R YA For R A In some embodiments, R YA For R YC r 6 Instances replace R B .

[0354] In some embodiments, R YA It is an oxo group, 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 selected from the following R B :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 carbon ring; and a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R B R YC r 6 Replace one instance.

[0355] In some embodiments, R YA It is a halogen, -CN, -OR, -NR2, -C(O)R, -C(O)OR, -C(O)NR2, -N(R)C(O)R, or selected from the following R B :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 carbon ring; and a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R B R YC r 6 Replace one instance.

[0356] In some embodiments, R YA It is a halogen, -CN, -OR, -NR2, -C(O)R, -C(O)OR, -C(O)NR2, -N(R)C(O)R, or selected from the following R B :C 1-6 Aliphatic chain; 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 carbon ring; and a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R B R YC r 6 Each instance is replaced. In some embodiments, R YA It is a halogen or selected from the following R B :C 1-6 Aliphatic chain; 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 carbon ring; and a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R B R YC r 6 Replace one instance.

[0357] In some embodiments, R YA It is a halogen or selected from the following R B :C 1-4 Aliphatic chain; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 5-membered saturated or partially unsaturated monocyclic carbon ring; and a 3- to 5-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R B R YC r 6 Each instance is replaced. In some embodiments, R YA It is a halogen or selected from the following R B :C 1-4 Aliphatic chain; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 5-membered saturated or partially unsaturated monocyclic carbon ring; and a 3- to 5-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R B r is independently selected from the following groups 6Examples of substitutions: oxo group, 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 groups.

[0358] In some embodiments, R YA It is a halogen or selected from the following R B :C 1-4 Aliphatic chain; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 5-membered saturated or partially unsaturated monocyclic carbon ring; and a 3- to 5-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R B r is independently selected from the following groups 6 Examples of substitutions: halogens, -CN-, -OH, -O- (optionally the C being substituted) 1-3 (Aliphatic group) and optionally substituted C 1-3 Aliphatic group. In some embodiments, R YA It is a halogen or selected from the following R B :C 1-4 Aliphatic chain; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 5-membered saturated or partially unsaturated monocyclic carbon ring; and a 3- to 5-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R B r is independently selected from the following groups 6 Examples of substitutions: halogens, -OH, -O-(C) 1-3 (aliphatic group) and C 1-3 Aliphatic groups, in which each C 1-3 The aliphatic group is optionally replaced by one to three halogens. In some embodiments, R YA It is a halogen or selected from the following R B :C 1-4Aliphatic chain; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 5-membered saturated or partially unsaturated monocyclic carbon ring; and a 3- to 5-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R B r is independently selected from the following groups 6 Examples of substitutions: fluorine, chlorine, -OH, -OCH3, -OCF3, -CH3, -CHF2, and -CF3.

[0359] In some embodiments, R YA It is a halogen or selected from the following R B :C 1-4 Aliphatic chains and 3- to 5-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the R B r is independently selected from the following groups 6 Examples of substitutions: halogens, -OH, -O-(C) 1-3 (aliphatic group) and C 1-3 Aliphatic groups, in which each C 1-3 The aliphatic group is optionally replaced by one to three halogens. In some embodiments, R YA It is a halogen or selected from the following R B :C 1-4 Aliphatic chains and 3- to 5-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen and oxygen; wherein the R B r is independently selected from the following groups 6 Examples of substitutions: fluorine, chlorine, -OH, -OCH3, -OCF3, -CH3, -CHF2, and -CF3.

[0360] In some embodiments, R YA It is a halogen or a C substituted with -OH and 0 to 3 fluorine atoms. 1-4 Aliphatic chains.

[0361] In some embodiments, R YA It can be halogen, -CN, -OR, -NR2, -C(O)R, -C(O)OR, -C(O)NR2, or -N(R)C(O)R. In some embodiments, R YA It is a halogen.

[0362] In some embodiments, R YA 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein RYA R YC r 6 Each instance is replaced. In some embodiments, R YA C 1-6 Aliphatic chain; 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 carbon ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R YA R YC r 6 Replace one instance.

[0363] In some embodiments, R YA C 1-4 Aliphatic chain; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 5-membered saturated or partially unsaturated monocyclic carbon ring; or a 3- to 5-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R YA R YC r 6 Each instance is replaced. In some embodiments, R YA C 1-4 Aliphatic chain; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 5-membered saturated or partially unsaturated monocyclic carbon ring; or a 3- to 5-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R YA r is independently selected from the following groups 6 Examples of substitutions: oxo group, 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 groups.

[0364] In some embodiments, R YA C 1-4Aliphatic chain; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 5-membered saturated or partially unsaturated monocyclic carbon ring; or a 3- to 5-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R YA r is independently selected from the following groups 6 Examples of substitutions: halogens, -CN-, -OH, -O- (optionally the C being substituted) 1-3 (Aliphatic group) and optionally substituted C 1-3 Aliphatic group. In some embodiments, R YA C 1-4 Aliphatic chain; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 5-membered saturated or partially unsaturated monocyclic carbon ring; or a 3- to 5-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R YA r is independently selected from the following groups 6 Examples of substitutions: halogens, -OH, -O-(C) 1-3 (aliphatic group) and C 1-3 Aliphatic groups, in which each C 1-3 The aliphatic group is optionally replaced by one to three halogens. In some embodiments, R YA C 1-4 Aliphatic chain; a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 5-membered saturated or partially unsaturated monocyclic carbon ring; or a 3- to 5-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R YA r is independently selected from the following groups 6 Examples of substitutions: fluorine, chlorine, -OH, -OCH3, -OCF3, -CH3, -CHF2, and -CF3.

[0365] In some embodiments, R YA C 1-4 Aliphatic chains or 3- to 5-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R YA r is independently selected from the following groups 6 Examples of substitutions: halogens, -OH, -O-(C) 1-3 (aliphatic group) and C 1-3 Aliphatic groups, in which each C 1-3 The aliphatic group is optionally replaced by one to three halogens. In some embodiments, R YA C 1-4Aliphatic chains or 3- to 5-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 independent heteroatoms selected from nitrogen and oxygen; wherein R YA r is independently selected from the following groups 6 Examples of substitutions include: fluorine, chlorine, -OH, -OCH3, -OCF3, -CH3, -CHF2, and -CF3. In some embodiments, R YA C substituted with -OH and 0 to 3 fluorine atoms 1-4 Aliphatic chains.

[0366] In some embodiments, R YA For 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, -O C(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.

[0367] In some embodiments, R YA For 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.

[0368] In some embodiments, R YA For oxidation. In some embodiments, R... YA It is a halogen. In some embodiments, R YA For -CN. In some embodiments, R YA For -NO2. In some embodiments, R YA For -OR. In some embodiments, R YA For -SR. In some embodiments, R YA For -NR2. In some embodiments, R YAFor -S(O)2R. In some embodiments, R YA It is -S(O)2NR2. In some embodiments, R YA It is -S(O)2F. In some embodiments, R YA For -S(O)R. In some embodiments, R YA For -S(O)NR2. In some embodiments, R YA For -S(O)(NR)R. In some embodiments, R YA For -C(O)R. In some embodiments, R YA For -C(O)OR. In some embodiments, R YA For -C(O)NR2. In some embodiments, R YA For -C(O)N(R)OR. In some embodiments, R YA For -OC(O)R. In some embodiments, R YA For -OC(O)NR2. In some embodiments, R YA It is -N(R)C(O)OR. In some embodiments, R YA It is -N(R)C(O)R. In some embodiments, R YA It is -N(R)C(O)NR2. In some embodiments, R YA For example, -N(R)C(NR)NR2. In some embodiments, R YA It is -N(R)S(O)2NR2. In some embodiments, R YA It is -N(R)S(O)2R. In some embodiments, R YA For -P(O)R2. In some embodiments, R YA For -P(O)(R)OR. In some embodiments, R YA =-B(OR)2. In some embodiments, R YA It is deuterium.

[0369] In some embodiments, R YA For 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.

[0370] In some embodiments, R YA It is a halogen, -CN, or -NO2. In some embodiments, R YA For -OR, -SR, or -NR2. In some embodiments, R YA It can be -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R YA It can be -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, R YA For -OC(O)R or -OC(O)NR2. In some embodiments, R YA It can be -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 YA It is either -P(O)R2 or -P(O)(R)OR.

[0371] In some embodiments, R YA For -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R YA It can be -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 YA 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.

[0372] In some embodiments, R YA It is -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R YA It is -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R YA It can be -SR, -S(O)2R, or -S(O)R. In some embodiments, R YA It is -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R YA It is -S(O)2NR2 or -S(O)NR2. In some embodiments, R YA It can be -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0373] In some embodiments, R YA It is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R YA It is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R YA It is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R YA It is -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R YA It is -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0374] In some embodiments, R YA For -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R YA It can be -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R YA It is -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0375] In some embodiments, R YA C 1-6 Aliphatic chain; phenyl; naphthyl; 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 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 R YC r 6 Replace one instance.

[0376] In some embodiments, R YA For R YC r 6 Instances replace C 1-6 Aliphatic group. In some embodiments, R YA For R YC r 6 One instance of substituted phenyl. In some embodiments, R YA For R YC r 6 One instance of naphthyl substitution. In some embodiments, RYA It 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 R YC r 6 Each instance is replaced. In some embodiments, R YA It is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R YC r 6 Each instance is replaced. In some embodiments, R YA For R YC r 6 Each instance replaces a 3- to 7-member saturated or partially unsaturated monocyclic carbon ring. In some embodiments, R YA For R YC r 6 Each instance replaces a 5- to 12-member saturated or partially unsaturated bicyclic carbon ring. In some embodiments, R YA It is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R YC r 6 Each instance is replaced. In some embodiments, R YA It 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 the ring is R YC r 6 Replace one instance.

[0377] In some embodiments, R YA It 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 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 R YC r 6 Replace one instance.

[0378] In some embodiments, R YA It 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 YC r 6 Each instance is replaced. In some embodiments, R YAIt is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; 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 R YC r 6 Replace one instance.

[0379] In some embodiments, R YA It is phenyl; naphthyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring or a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; each of which is R YC r 6 Each instance is replaced. In some embodiments, R YA It 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 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 R YC r 6 Replace one instance.

[0380] In some embodiments, R YA It is a phenyl group; 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R YC r 6 Each instance is replaced. In some embodiments, R YA It is a naphthyl group; 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R YC r 6 Replace one instance.

[0381] In some embodiments, R YA It is phenyl or naphthyl; each of them is R YC r 6 Each instance is replaced. In some embodiments, R YAIt 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 R YC r 6 Each instance is replaced. In some embodiments, R YA It consists of 3 to 7 saturated or partially unsaturated monocyclic carbon rings or 5 to 12 saturated or partially unsaturated bicyclic carbon rings; each is respectively bound by R YC r 6 Each instance is replaced. In some embodiments, R YA It 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 R YC r 6 Replace one instance.

[0382] In some embodiments, R YA It is a phenyl group 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 YC r 6 Each instance is replaced. In some embodiments, R YA It is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 independent heteroatoms selected from nitrogen, oxygen, and sulfur; each of which is R YC r 6 Each instance is replaced. In some embodiments, R YA It is a naphthyl group 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 YC r 6 Each instance is replaced. In some embodiments, R YA It is a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring 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 R YC r 6 Replace one instance.

[0383] In some embodiments, R YA It is a phenyl or a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring; each of them is R YC r 6 Each instance is replaced. In some embodiments, R YA It is a naphthyl or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; each of them is R YC r 6 Each instance is replaced. In some embodiments, RYA It 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R YC r 6 Each instance is replaced. In some embodiments, R YA It 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R YC r 6 Replace one instance.

[0384] In some embodiments, R YA C 1-6 Aliphatic chains; 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings; 5- to 12-membered saturated or partially unsaturated bicyclic carbon rings; 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 7- to 12-membered saturated or partially unsaturated bicyclic heterocycles having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R YC r 6 Each instance is replaced. In some embodiments, R YA C 1-6 Aliphatic chain; phenyl; naphthyl; 3 to 7 membered saturated or partially unsaturated monocyclic carbon ring; or 5 to 12 membered saturated or partially unsaturated bicyclic carbon ring; each of which is R YC r 6 Each instance is replaced. In some embodiments, R YA 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R YC r 6 Replace one instance.

[0385] In some embodiments, R YA C 1-6 Aliphatic chains, 3 to 7-membered saturated or partially unsaturated monocyclic carbon rings, or 5 to 12-membered saturated or partially unsaturated bicyclic carbon rings; each is respectively bound by R YC r 6 Each instance is replaced. In some embodiments, R YA C 1-6Aliphatic chains, 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings, or 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 independent heteroatoms selected from nitrogen, oxygen, and sulfur; each of which is R YC r 6 Each instance is replaced. In some embodiments, R YA C 1-6 Aliphatic chains, phenyl groups, or 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings; each of which is R YC r 6 Replace one instance.

[0386] In some embodiments, R YA It is an 8- to 10-membered bicyclic heteroaryl ring having one, two, or three heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R YC r 6 Each instance is replaced. In some embodiments, R YA It is an 8- to 10-membered bicyclic heteroaryl ring having 2 or 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R YC r 6 Each instance is replaced. In some embodiments, R YA It is an 8- to 10-membered bicyclic heteroaryl ring having 1, 2, or 3 nitrogen atoms; wherein the ring is R YC r 6 Each instance is replaced. In some embodiments, R YA It is an 8- to 10-membered bicyclic heteroaryl ring having 2 or 3 nitrogen atoms; wherein the ring is R YC r 6 Replace one instance.

[0387] In some embodiments, R YA It is imidazo[1,2-a]pyrazinyl, [1,2,4]triazolo[1,5-a]pyridyl, or pyrazolo[1,5-a]pyrimidinyl; each of which is R YC r 6 An instance is replaced. In some embodiments, R YA For R YC r 6 One example is a substituted imidazo[1,2-a]pyrazinyl group. In some embodiments, R YA For R YC r 6 One example is a substituted [1,2,4]triazolo[1,5-a]pyridyl group. In some embodiments, R YA For R YC r 6 One example is a substituted pyrazolo[1,5-a]pyrimidinyl group.

[0388] In some embodiments, RYA It is imidazo[1,2-a]pyrazin-6-yl, [1,2,4]triazolo[1,5-a]pyridin-6-yl, or pyrazolo[1,5-a]pyrimidine-5-yl; each of which is R YC r 6 An instance is replaced. In some embodiments, R YA For R YC r 6 One example is a substituted imidazo[1,2-a]pyrazin-6-yl. In some embodiments, R YA For R YC r 6 One example is a substituted [1,2,4]triazolo[1,5-a]pyridin-6-yl. In some embodiments, R YA For R YC r 6 One example is a substituted pyrazolo[1,5-a]pyrimidin-5-yl.

[0389] In some embodiments, R YA It is imidazo[1,2-a]pyrazin-6-yl, [1,2,4]triazolo[1,5-a]pyridin-6-yl, or pyrazolo[1,5-a]pyrimidin-5-yl. In some embodiments, R YA It is imidazo[1,2-a]pyrazin-6-yl. In some embodiments, R YA It is [1,2,4]triazolo[1,5-a]pyridin-6-yl. In some embodiments, R YA It is pyrazolo[1,5-a]pyrimidin-5-yl.

[0390] In some embodiments, R YA It is a 5- to 6-membered monocyclic heteroaryl ring having 1, 2, or 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 5- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 or 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R YC r 6 Replace one instance.

[0391] In some embodiments, R YA It is a 5- to 6-membered monocyclic heteroaryl ring having 1, 2, or 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R YC r 6 Each instance is replaced. In some embodiments, R YA It is a 5-membered monocyclic heteroaryl ring having 1, 2, or 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R YC r 6 Each instance is replaced. In some embodiments, R YAIt is a 5-membered monocyclic heteroaryl ring having one or two heteroatoms independently selected from nitrogen and oxygen; wherein the ring is R YC r 6 Each instance is replaced. In some embodiments, R YA It is a 6-membered monocyclic heteroaryl ring having 1 or 2 nitrogen atoms; wherein the ring is R YC r 6 Replace one instance.

[0392] In some embodiments, R YA It is either pyrazolyl or imidazole, each of which is converted by R YC r 6 An instance is replaced. In some embodiments, R YA For R YC r 6 One instance of substituted pyrazole group. In some embodiments, R YA For R YC r 6 One instance of substituted imidazole group. In some embodiments, R YA It is either pyrazol-4-yl or imidazole-4-yl, each of which is R YC r 6 An instance is replaced. In some embodiments, R YA For R YC r 6 One instance of substituted pyrazole-4-yl. In some embodiments, R YA For R YC r 6 One instance of substituted imidazole-4-yl.

[0393] In some embodiments, R YA It is a 3- to 7-membered partially unsaturated monocyclic heterocycle having one or two independent heteroatoms selected from nitrogen, oxygen, and sulfur; wherein the ring is R YC r 6 Each instance is replaced. In some embodiments, R YA It is a 3- to 7-membered saturated monocyclic heterocycle having one or two independent heteroatoms selected from nitrogen, oxygen, and sulfur; wherein the ring is R YC r 6 Replace one instance.

[0394] In some embodiments, R YA It is a 5- to 7-membered saturated or partially unsaturated monocyclic heterocycle having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R YC r 6 Each instance is replaced. In some embodiments, R YA It is a 5- to 7-membered saturated monocyclic heterocycle having one or two independent heteroatoms selected from nitrogen, oxygen, and sulfur; wherein the ring is RYC r 6 Each instance is replaced. In some embodiments, R YA It is a 5- to 7-membered partially unsaturated monocyclic heterocycle having one or two independent heteroatoms selected from nitrogen, oxygen, and sulfur; wherein the ring is R YC r 6 Replace one instance.

[0395] In some embodiments, R YA It is a 6-membered saturated or partially unsaturated monocyclic heterocycle having one or two independent heteroatoms selected from nitrogen and oxygen; wherein the ring is R YC r 6 Each instance is replaced. In some embodiments, R YA It is a 6-membered saturated monocyclic heterocycle having one or two heteroatoms independently selected from nitrogen and oxygen; wherein the ring is R YC r 6 Each instance is replaced. In some embodiments, R YA It is a 6-membered partially unsaturated monocyclic heterocycle having one or two independent heteroatoms selected from nitrogen and oxygen; wherein the ring is R YC r 6 Each instance is replaced. In some embodiments, R YA For R YC The pyridine-2(1H)-keto group is substituted with 0, 1, 2, or 3 instances. In some embodiments, R YA For R YC 0, 1, 2 or 3 instances of substituted pyridin-2(1H)-one-5-yl.

[0396] In some embodiments, R YA for Where R YC and r 6 As defined in the embodiments and categories and subclasses herein. In some embodiments, R YA for In some embodiments, R YA for In some embodiments, R YA for

[0397] In some embodiments, R YA for Where R YC As defined in the embodiments and categories and subclasses herein. In some embodiments, R YA for In some embodiments, R YA for

[0398] In some embodiments, R YA for In some embodiments, R YA for In some embodiments, R YA for In some embodiments, R YA for In some embodiments, R YA for In some embodiments, R YA for

[0399] In some embodiments, R YA for In some embodiments, R YA for In some embodiments, R YA for In some embodiments, R YA for In some embodiments, R YA for In some embodiments, R YA for

[0400] In some embodiments, R YA The groups are selected from those described in the compounds in Table 1.

[0401] As generally defined above, R ZA For R ZC r 7 Instances replace R A or R B In some embodiments, R ZA For R A In some embodiments, R ZA For R ZC r 7 Instances replace R B .

[0402] In some embodiments, R ZAIt is an oxo group, 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 selected from the following R B :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 carbon ring; and a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R B R ZC r 7 Replace one instance.

[0403] In some embodiments, R ZA It is a halogen, -CN, -OR, -NR2, -C(O)R, -C(O)OR, -C(O)NR2, -N(R)C(O)R, or selected from the following R B :C 1-6 Aliphatic chain; 3 to 7 member saturated or partially unsaturated monocyclic carbon rings; and 3 to 7 member saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R B R ZC r 7 Each instance is replaced. In some embodiments, R ZA It is a halogen or selected from the following R B :C 1-4 Aliphatic chain; 3- to 5-membered saturated or partially unsaturated monocyclic carbon ring; and 3- to 5-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R B r is independently selected from the following groups 7Examples of substitutions: oxo group, 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 Aliphatic groups.

[0404] In some embodiments, R ZA It is a halogen or selected from the following R B :C 1-4 Aliphatic chain; 3- to 5-membered saturated or partially unsaturated monocyclic carbon ring; and 3- to 5-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R B r is independently selected from the following groups 7 Examples of substitutions: halogens, -OH, -O-(C) 1-3 (aliphatic group) and C 1-3 Aliphatic groups, in which each C 1-3 The aliphatic group is optionally replaced by one to three halogens. In some embodiments, R ZA It is a halogen or selected from the following R B :C 1-4 Aliphatic chain; 3- to 5-membered saturated or partially unsaturated monocyclic carbon ring; and 3- to 5-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R B r is independently selected from the following groups 7 Examples of substitutions: fluorine, chlorine, -OH, -OCH3, -OCF3, -CH3, -CHF2, and -CF3.

[0405] In some embodiments, R ZA It can be halogen, -CN, -OR, -NR2, -C(O)R, -C(O)OR, -C(O)NR2, or -N(R)C(O)R. In some embodiments, R ZA It is a halogen.

[0406] In some embodiments, R ZA C 1-6Aliphatic chain; 3 to 7 member saturated or partially unsaturated monocyclic carbon ring; or 3 to 7 member saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R ZA R ZC r 7 Each instance is replaced. In some embodiments, R ZA C 1-4 Aliphatic chain; 3- to 5-membered saturated or partially unsaturated monocyclic carbon ring; or 3- to 5-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R ZA r is independently selected from the following groups 7 Examples of substitutions: oxo group, 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 groups.

[0407] In some embodiments, R ZA C 1-4 Aliphatic chain; 3- to 5-membered saturated or partially unsaturated monocyclic carbon ring; or 3- to 5-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R ZA r is independently selected from the following groups 7 Examples of substitutions: halogens, -OH, -O-(C) 1-3 (aliphatic group) and C 1-3 Aliphatic groups, in which each C 1-3 The aliphatic group is optionally replaced by one to three halogens. In some embodiments, R ZA C 1-4 Aliphatic chain; 3- to 5-membered saturated or partially unsaturated monocyclic carbon ring; or 3- to 5-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R ZA r is independently selected from the following groups 7 Examples of substitutions: fluorine, chlorine, -OH, -OCH3, -OCF3, -CH3, -CHF2, and -CF3.

[0408] In some embodiments, RZA For 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, -O C(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.

[0409] In some embodiments, R ZA For 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.

[0410] In some embodiments, R ZA For oxidation. In some embodiments, R... ZA It is a halogen. In some embodiments, R ZA For -CN. In some embodiments, R ZA For -NO2. In some embodiments, R ZA For -OR. In some embodiments, R ZA For -SR. In some embodiments, R ZA For -NR2. In some embodiments, R ZA For -S(O)2R. In some embodiments, R ZA It is -S(O)2NR2. In some embodiments, R ZA It is -S(O)2F. In some embodiments, R ZA For -S(O)R. In some embodiments, R ZA For -S(O)NR2. In some embodiments, R ZA For -S(O)(NR)R. In some embodiments, R ZA For -C(O)R. In some embodiments, R ZAFor -C(O)OR. In some embodiments, R ZA For -C(O)NR2. In some embodiments, R ZA For -C(O)N(R)OR. In some embodiments, R ZA For -OC(O)R. In some embodiments, R ZA For -OC(O)NR2. In some embodiments, R ZA It is -N(R)C(O)OR. In some embodiments, R ZA It is -N(R)C(O)R. In some embodiments, R ZA It is -N(R)C(O)NR2. In some embodiments, R ZA For example, -N(R)C(NR)NR2. In some embodiments, R ZA It is -N(R)S(O)2NR2. In some embodiments, R ZA It is -N(R)S(O)2R. In some embodiments, R ZA For -P(O)R2. In some embodiments, R ZA For -P(O)(R)OR. In some embodiments, R ZA =-B(OR)2. In some embodiments, R ZA It is deuterium.

[0411] In some embodiments, R ZA For 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.

[0412] In some embodiments, R ZA It is a halogen, -CN, or -NO2. In some embodiments, R ZA For -OR, -SR, or -NR2. In some embodiments, R ZA It can be -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R ZA It can be -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, RZA For -OC(O)R or -OC(O)NR2. In some embodiments, R ZA It can be -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 ZA It is either -P(O)R2 or -P(O)(R)OR.

[0413] In some embodiments, R ZA For -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R ZA It can be -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 ZA 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.

[0414] In some embodiments, R ZA It is -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R ZA It is -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R ZA It can be -SR, -S(O)2R, or -S(O)R. In some embodiments, R ZA It is -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R ZA It is -S(O)2NR2 or -S(O)NR2. In some embodiments, R ZA It can be -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0415] In some embodiments, R ZA It is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R ZA It is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R ZA It is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R ZA It is -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R ZAIt is -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0416] In some embodiments, R ZA For -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R ZA It can be -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R ZA It is -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0417] In some embodiments, R ZA C 1-6 Aliphatic chain; phenyl; naphthyl; 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 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 R ZC r 7 Replace one instance.

[0418] In some embodiments, R ZA For R ZC r 7 Instances replace C 1-6 Aliphatic group. In some embodiments, R ZA For R ZC r 7 One instance of substituted phenyl. In some embodiments, R ZA For R ZC r 7 One instance of naphthyl substitution. In some embodiments, R ZA It 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 R ZC r 7 Each instance is replaced. In some embodiments, R ZA It is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R ZC r 7 Each instance is replaced. In some embodiments, R ZA For R ZC r7 Each instance replaces a 3- to 7-member saturated or partially unsaturated monocyclic carbon ring. In some embodiments, R ZA For R ZC r 7 Each instance replaces a 5- to 12-member saturated or partially unsaturated bicyclic carbon ring. In some embodiments, R ZA It is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R ZC r 7 Each instance is replaced. In some embodiments, R ZA It 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 the ring is R ZC r 7 Replace one instance.

[0419] In some embodiments, R ZA It 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 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 R ZC r 7 Replace one instance.

[0420] In some embodiments, R ZA It 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 ZC r 7 Each instance is replaced. In some embodiments, R ZA It is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; 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 R ZC r 7 Replace one instance.

[0421] In some embodiments, R ZAIt is phenyl; naphthyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring; or a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; each of which is R ZC r 7 Each instance is replaced. In some embodiments, R ZA It 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 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 R ZC r 7 Replace one instance.

[0422] In some embodiments, R ZA It is a phenyl group; 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R ZC r 7 Each instance is replaced. In some embodiments, R ZA It is a naphthyl group; 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R ZC r 7 Replace one instance.

[0423] In some embodiments, R ZA It is phenyl or naphthyl; each of them is R ZC r 7 Each instance is replaced. In some embodiments, R ZA It 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 R ZC r 7 Each instance is replaced. In some embodiments, R ZA It consists of 3 to 7 saturated or partially unsaturated monocyclic carbon rings or 5 to 12 saturated or partially unsaturated bicyclic carbon rings; each is respectively bound by R ZC r 7 Each instance is replaced. In some embodiments, R ZAIt 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 R ZC r 7 Replace one instance.

[0424] In some embodiments, R ZA It is a phenyl group 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 ZC r 7 Each instance is replaced. In some embodiments, R ZA It is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 independent heteroatoms selected from nitrogen, oxygen, and sulfur; each of which is R ZC r 7 Each instance is replaced. In some embodiments, R ZA It is a naphthyl group 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 ZC r 7 Each instance is replaced. In some embodiments, R ZA It is a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring 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 R ZC r 7 Replace one instance.

[0425] In some embodiments, R ZA It is a phenyl or a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring; each of them is R ZC r 7 Each instance is replaced. In some embodiments, R ZA It is a naphthyl or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; each of them is R ZC r 7 Each instance is replaced. In some embodiments, R ZA It 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R ZC r 7 Each instance is replaced. In some embodiments, R ZA It 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is RZC r 7 Replace one instance.

[0426] In some embodiments, R ZA C 1-6 Aliphatic chains; 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings; 5- to 12-membered saturated or partially unsaturated bicyclic carbon rings; 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 7- to 12-membered saturated or partially unsaturated bicyclic heterocycles having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R ZC r 7 Each instance is replaced. In some embodiments, R ZA C 1-6 Aliphatic chain; phenyl; naphthyl; 3 to 7 membered saturated or partially unsaturated monocyclic carbon ring; or 5 to 12 membered saturated or partially unsaturated bicyclic carbon ring; each of which is R ZC r 7 Each instance is replaced. In some embodiments, R ZA 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R ZC r 7 Replace one instance.

[0427] In some embodiments, R ZA C 1-6 Aliphatic chains, 3 to 7-membered saturated or partially unsaturated monocyclic carbon rings, or 5 to 12-membered saturated or partially unsaturated bicyclic carbon rings; each is respectively bound by R ZC r 7 Each instance is replaced. In some embodiments, R ZA C 1-6 Aliphatic chains, 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings, or 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 independent heteroatoms selected from nitrogen, oxygen, and sulfur; each of which is R ZC r 7 Each instance is replaced. In some embodiments, R ZA C 1-6 Aliphatic chains, phenyl groups, or 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings; each of which is R ZC r 7 Replace one instance.

[0428] In some embodiments, R ZA The groups are selected from those described in the compounds in Table 1.

[0429] As generally defined above, R L For R LC r 8 Instances replace R A or R B In some embodiments, R L For R A In some embodiments, R L For R LC r 8 Instances replace R B .

[0430] In some embodiments, R L For 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, -O C(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.

[0431] In some embodiments, R L For 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.

[0432] In some embodiments, R L For oxidation. In some embodiments, R... L It is a halogen. In some embodiments, R L For -CN. In some embodiments, R L For -NO2. In some embodiments, R L For -OR. In some embodiments, R L For -SR. In some embodiments, R LFor -NR2. In some embodiments, R L For -S(O)2R. In some embodiments, R L It is -S(O)2NR2. In some embodiments, R L It is -S(O)2F. In some embodiments, R L For -S(O)R. In some embodiments, R L For -S(O)NR2. In some embodiments, R L For -S(O)(NR)R. In some embodiments, R L For -C(O)R. In some embodiments, R L For -C(O)OR. In some embodiments, R L For -C(O)NR2. In some embodiments, R L For -C(O)N(R)OR. In some embodiments, R L For -OC(O)R. In some embodiments, R L For -OC(O)NR2. In some embodiments, R L It is -N(R)C(O)OR. In some embodiments, R L It is -N(R)C(O)R. In some embodiments, R L It is -N(R)C(O)NR2. In some embodiments, R L For example, -N(R)C(NR)NR2. In some embodiments, R L It is -N(R)S(O)2NR2. In some embodiments, R L It is -N(R)S(O)2R. In some embodiments, R L For -P(O)R2. In some embodiments, R L For -P(O)(R)OR. In some embodiments, R L =-B(OR)2. In some embodiments, R L It is deuterium.

[0433] In some embodiments, R LFor 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.

[0434] In some embodiments, R L It is a halogen, -CN, or -NO2. In some embodiments, R L For -OR, -SR, or -NR2. In some embodiments, R L It can be -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 It can be -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, R L For -OC(O)R or -OC(O)NR2. In some embodiments, R L It can be -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 It is either -P(O)R2 or -P(O)(R)OR.

[0435] In some embodiments, R L For -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R L It can be -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.

[0436] In some embodiments, R L It is -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R LIt is -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R L It can be -SR, -S(O)2R, or -S(O)R. In some embodiments, R L It is -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R L It is -S(O)2NR2 or -S(O)NR2. In some embodiments, R L It can be -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0437] In some embodiments, R L It is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R L It is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R L It is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R L It is -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R L It is -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0438] In some embodiments, R L For -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R L It can be -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R L It is -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0439] In some embodiments, R L C 1-6 Aliphatic chain; phenyl; naphthyl; 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 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 R LC r 8 Replace one instance.

[0440] In some embodiments, R L For R LC r 8 Instances replace C 1-6 Aliphatic group. In some embodiments, R L For R LC r 8 One instance of substituted phenyl. In some embodiments, R L For R LC r 8 One instance of naphthyl substitution. In some embodiments, R L It 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 R LC r 8 Each instance is replaced. In some embodiments, R L It is an 8- to 10-membered bicyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R LC r 8 Each instance is replaced. In some embodiments, R L For R LC r 8 Each instance replaces a 3- to 7-member saturated or partially unsaturated monocyclic carbon ring. In some embodiments, R L For R LC r 8 Each instance replaces a 5- to 12-member saturated or partially unsaturated bicyclic carbon ring. In some embodiments, R L It is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the ring is R LC r 8 Each instance is replaced. In some embodiments, R L It 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 the ring is R LC r 8 Replace one instance.

[0441] In some embodiments, R LIt 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 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 R LC r 8 Replace one instance.

[0442] In some embodiments, R L It 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 LC r 8 Each instance is replaced. In some embodiments, R L It is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; 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 R LC r 8 Replace one instance.

[0443] In some embodiments, R L It is phenyl; naphthyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring; or a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; each of which is R LC r 8 Each instance is replaced. In some embodiments, R L It 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 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 R LC r 8 Replace one instance.

[0444] In some embodiments, R LIt is a phenyl group; 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R LC r 8 Each instance is replaced. In some embodiments, R L It is a naphthyl group; 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R LC r 8 Replace one instance.

[0445] In some embodiments, R L It is phenyl or naphthyl; each of them is R LC r 8 Each instance is replaced. In some embodiments, R L It 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 R LC r 8 Each instance is replaced. In some embodiments, R L It consists of 3 to 7 saturated or partially unsaturated monocyclic carbon rings or 5 to 12 saturated or partially unsaturated bicyclic carbon rings; each is respectively bound by R LC r 8 Each instance is replaced. In some embodiments, R L It 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 R LC r 8 Replace one instance.

[0446] In some embodiments, R L It is a phenyl group 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 LC r 8 Each instance is replaced. In some embodiments, R L It is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 independent heteroatoms selected from nitrogen, oxygen, and sulfur; each of which is R LC r 8 Each instance is replaced. In some embodiments, RL It is a naphthyl group 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 LC r 8 Each instance is replaced. In some embodiments, R L It is a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring 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 R LC r 8 Replace one instance.

[0447] In some embodiments, R L It is a phenyl or a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring; each of them is R LC r 8 Each instance is replaced. In some embodiments, R L It is a naphthyl or a 5- to 12-membered saturated or partially unsaturated bicyclic carbocyclic ring; each of them is R LC r 8 Each instance is replaced. In some embodiments, R L It 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R LC r 8 Each instance is replaced. In some embodiments, R L It 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R LC r 8 Replace one instance.

[0448] In some embodiments, R L C 1-6 Aliphatic chains; 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings; 5- to 12-membered saturated or partially unsaturated bicyclic carbon rings; 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 7- to 12-membered saturated or partially unsaturated bicyclic heterocycles having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R LC r 8 Each instance is replaced. In some embodiments, R L C 1-6 Aliphatic chain; phenyl; naphthyl; 3 to 7 membered saturated or partially unsaturated monocyclic carbon ring; or 5 to 12 membered saturated or partially unsaturated bicyclic carbon ring; each of which is R LC r 8Each instance is replaced. In some embodiments, R L 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is R LC r 8 Replace one instance.

[0449] In some embodiments, R L C 1-6 Aliphatic chains, 3 to 7-membered saturated or partially unsaturated monocyclic carbon rings, or 5 to 12-membered saturated or partially unsaturated bicyclic carbon rings; each is respectively bound by R LC r 8 Each instance is replaced. In some embodiments, R L C 1-6 Aliphatic chains, 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings, or 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 independent heteroatoms selected from nitrogen, oxygen, and sulfur; each of which is R LC r 8 Each instance is replaced. In some embodiments, R L C 1-6 Aliphatic chains, phenyl groups, or 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings; each of which is R LC r 8 Replace one instance.

[0450] In some embodiments, R L The groups are selected from those described in the compounds in Table 1.

[0451] As generally defined above, R A Each instance is independently an oxo group, 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.

[0452] In some embodiments, R AEach instance is independently an oxo group, 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.

[0453] In some embodiments, R A For oxidation. In some embodiments, R... A It is a halogen. In some embodiments, R A For -CN. In some embodiments, R A For -NO2. In some embodiments, R A For -OR. In some embodiments, R A -SF5. In some embodiments, R A For -SR. In some embodiments, R A For -NR2. In some embodiments, R A For -S(O)2R. In some embodiments, R A It is -S(O)2NR2. In some embodiments, R A It is -S(O)2F. In some embodiments, R A For -S(O)R. In some embodiments, R A For -S(O)NR2. In some embodiments, R A For -S(O)(NR)R. In some embodiments, R A For -C(O)R. In some embodiments, R A For -C(O)OR. In some embodiments, R A For -C(O)NR2. In some embodiments, R A For -C(O)N(R)OR. In some embodiments, R A For -OC(O)R. In some embodiments, R A For -OC(O)NR2. In some embodiments, R A It is -N(R)C(O)OR. In some embodiments, R A It is -N(R)C(O)R. In some embodiments, R A It is -N(R)C(O)NR2. In some embodiments, RA For example, -N(R)C(NR)NR2. In some embodiments, R A It is -N(R)S(O)2NR2. In some embodiments, R A It is -N(R)S(O)2R. In some embodiments, R A For -P(O)R2. In some embodiments, R A For -P(O)(R)OR. In some embodiments, R A =-B(OR)2. In some embodiments, R A It is deuterium.

[0454] In some embodiments, R A For 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.

[0455] In some embodiments, R A It is a halogen, -CN, or -NO2. In some embodiments, R A For -OR, -SR, or -NR2. In some embodiments, R A It can be -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 It can be -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, R A For -OC(O)R or -OC(O)NR2. In some embodiments, R A It can be -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 It is either -P(O)R2 or -P(O)(R)OR.

[0456] In some embodiments, R A For -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, RA It can be -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 A 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.

[0457] In some embodiments, R A It is -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R A It is -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R A It can be -SR, -S(O)2R, or -S(O)R. In some embodiments, R A It is -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R A It is -S(O)2NR2 or -S(O)NR2. In some embodiments, R A It can be -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0458] In some embodiments, R A It is -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R A It is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R A It is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R A It is -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R A It is -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0459] In some embodiments, R A For -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R A It can be -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R A It is -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0460] In some embodiments, R A The groups are selected from those described in the compounds in Table 1.

[0461] As generally defined above, R B Each instance is independently C 1-6 Aliphatic chain; phenyl; naphthyl; cubic; 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 carbon ring; 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 7- to 12-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0462] In some embodiments, R B C 1-6 Aliphatic chain. In some embodiments, R B It is phenyl. In some embodiments, R B It is a naphthyl group. In some embodiments, R B It is a cubic alkyl group. In some embodiments, R B It is an adamantyl alkyl group. In some embodiments, R B It 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 B It is 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 It is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring. In some embodiments, R B It is a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring. In some embodiments, R B It is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B It is a 7- to 12-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0463] In some embodiments, R BIt 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 carbon ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; 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.

[0464] In some embodiments, R B It 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 B It is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring; a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring; 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.

[0465] In some embodiments, R B It is phenyl; naphthyl; a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring or a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring. In some embodiments, R B It 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 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.

[0466] In some embodiments, R B It is a phenyl group; 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B It is a naphthyl group; 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 carbon ring; or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0467] In some embodiments, R BIt is phenyl or naphthyl. In some embodiments, R B It 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. In some embodiments, R B It is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring or a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring. In some embodiments, R B It 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.

[0468] In some embodiments, R B It is a phenyl group or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B It is a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B It is a naphthyl group 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 It is a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring or a 7- to 12-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0469] In some embodiments, R B It is a phenyl or a 3- to 7-membered saturated or partially unsaturated monocyclic carbon ring. In some embodiments, R B It is a naphthyl group or a 5- to 12-membered saturated or partially unsaturated bicyclic carbon ring. In some embodiments, R B It 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 heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B It 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 heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0470] In some embodiments, R B C 1-6Aliphatic chains; 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings; 5- to 12-membered saturated or partially unsaturated bicyclic carbon rings; 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 7- to 12-membered saturated or partially unsaturated bicyclic heterocycles having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B C 1-6 Aliphatic chain; phenyl; naphthyl; 3 to 7 member saturated or partially unsaturated monocyclic carbon ring; or 5 to 12 member saturated or partially unsaturated bicyclic carbon ring. In some embodiments, R B 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 carbon ring; or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0471] In some embodiments, R B C 1-6 Aliphatic chains, 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings, or 5- to 12-membered saturated or partially unsaturated bicyclic carbon rings. In some embodiments, R B C 1-6 Aliphatic chains, 3- to 7-membered saturated or partially unsaturated monocyclic carbon rings, or 3- to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R B C 1-6 Aliphatic chains, phenyl groups, or 3 to 7 nucleotide saturated or partially unsaturated monocyclic carbon rings.

[0472] In some embodiments, R B The groups are selected from those described in the compounds in Table 1.

[0473] As generally defined above, R 1C Each instance is independently an oxo group, 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 an optionally substituted group selected from the following: C 1-6Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0474] In some embodiments, R 1C Each instance is independently an oxo group, 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 an optionally substituted group selected from the following: C 1-6 Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0475] In some embodiments, R 1C Each instance is independently an oxo group, 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 instance is independently selected from the following substituted groups: C 1-6 Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0476] In some embodiments, R 1C For oxidation. In some embodiments, R... 1C For deuterium. In some embodiments, R1C Each instance is independently a halogen. In some embodiments, R 1C For -CN. In some embodiments, R 1C For -NO2. In some embodiments, R 1C For -OR. In some embodiments, R 1C For -SR. In some embodiments, R 1C For -NR2. In some embodiments, R 1C For -S(O)2R. In some embodiments, R 1C It is -S(O)2NR2. In some embodiments, R 1C It is -S(O)2F. In some embodiments, R 1C For -S(O)R. In some embodiments, R 1C For -S(O)NR2. In some embodiments, R 1C For -S(O)(NR)R. In some embodiments, R 1C For -C(O)R. In some embodiments, R 1C For -C(O)OR. In some embodiments, R 1C For -C(O)NR2. In some embodiments, R 1C For -C(O)N(R)OR. In some embodiments, R 1C For -OC(O)R. In some embodiments, R 1C For -OC(O)NR2. In some embodiments, R 1C It is -N(R)C(O)OR. In some embodiments, R 1C It is -N(R)C(O)R. In some embodiments, R 1C It is -N(R)C(O)NR2. In some embodiments, R 1C For example, -N(R)C(NR)NR2. In some embodiments, R 1C It is -N(R)S(O)2NR2. In some embodiments, R 1C It is -N(R)S(O)2R. In some embodiments, R 1C For -P(O)R2. In some embodiments, R 1C For -P(O)(R)OR. In some embodiments, R 1C It is -B(OR)2.

[0477] In some embodiments, R 1CEach instance 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.

[0478] In some embodiments, R 1C Each instance is independently halogenated, -CN, or -NO2. In some embodiments, R 1C Each instance is independently -OR, -SR, or -NR2. In some embodiments, R 1C Each instance 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, R 1C Each instance is independently -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, R 1C Each instance is independently -OC(O)R or -OC(O)NR2. In some embodiments, R 1C Each instance 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 instance is independently -P(O)R2 or -P(O)(R)OR.

[0479] In some embodiments, R 1C Each instance is independently -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R 1C Each instance 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 instance 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.

[0480] In some embodiments, R 1C Each instance is independently -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R 1C Each instance is independently -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 1C Each instance is independently -SR, -S(O)2R, or -S(O)R. In some embodiments, R 1C Each instance is independently -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 1C Each instance is independently -S(O)2NR2 or -S(O)NR2. In some embodiments, R 1C Each instance is independently -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0481] In some embodiments, R 1C Each instance is independently -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R 1C Each instance is independently -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R 1C Each instance is independently -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R 1C Each instance is independently -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R 1C Each instance is independently -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0482] In some embodiments, R 1C Each instance 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 instance is independently -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R 1C Each instance is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0483] In some embodiments, R 1C Each instance is independently a C that can be arbitrarily replaced. 1-6 Aliphatic group. In some embodiments, R 1CEach instance is independently a optionally substituted phenyl group. In some embodiments, R 1C Each instance is independently a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having one or two independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 1C Each instance is independently a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur.

[0484] In some embodiments, R 1C Each instance is independently a C that can be arbitrarily replaced. 1-6 An aliphatic group or an optionally substituted 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having one or two independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 1C Each example is independently a 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.

[0485] In some embodiments, R 1C Each instance is independently a C that can be arbitrarily replaced. 1-6 Aliphatic group or optionally substituted phenyl group. In some embodiments, R 1C Each instance 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.

[0486] In some embodiments, R 1C Each example is independently selected from the following optionally substituted groups: phenyl, 3 to 7 membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6 membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0487] In some embodiments, R 1C Each instance is independently C 1-6 Aliphatic group. In some embodiments, R 1C It is phenyl. In some embodiments, R 1C Each instance 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. In some embodiments, R 1C Each instance is independently a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0488] In some embodiments, R 1C Each instance is independently C1-6 An aliphatic group or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 1C Each instance is independently a phenyl or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0489] In some embodiments, R 1C Each instance is independently C 1-6 Aliphatic group or phenyl. In some embodiments, R 1C Each instance 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.

[0490] In some embodiments, R 1C Each example is independently a phenyl ring, 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.

[0491] In some embodiments, R 1C Each instance is independently a halogen, -CN, -O- (optionally substituted C). 1-6 (Aliphatic group) or optionally substituted C 1-6 Aliphatic group. In some embodiments, R 1C Each instance is independently a halogen, -CN, -O-(C 1-6 (Aliphatic group) or C 1-6 Aliphatic groups; where each C 1-6 The aliphatic group is optionally substituted with one or more halogen atoms. In some embodiments, R 1C Each instance is independently a halogen or optionally a C substituted with one to three halogens. 1-3 Aliphatic group. In some embodiments, R 1C Each instance is independently fluorine, chlorine, -CH3, -CHF2, or -CF3.

[0492] In some embodiments, R 1CEach instance is independently an oxo group, 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 groups.

[0493] In some embodiments, R 1C Each example is independently selected from the groups described in the compounds in Table 1.

[0494] As generally defined above, R 2C Each instance is independently an oxo group, 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 an optionally substituted group selected from the following: C 1-6 Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0495] In some embodiments, R 2CEach instance is independently an oxo group, 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 an optionally substituted group selected from the following: C 1-6 Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0496] In some embodiments, R 2C Each instance is independently an oxo group, 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 instance is independently selected from the following substituted groups: C 1-6 Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0497] In some embodiments, R 2C For oxidation. In some embodiments, R... 2C For deuterium. In some embodiments, R 2C Each instance is independently a halogen. In some embodiments, R 2C For -CN. In some embodiments, R 2C For -NO2. In some embodiments, R 2C For -OR. In some embodiments, R 2CFor -SR. In some embodiments, R 2C For -NR2. In some embodiments, R 2C For -S(O)2R. In some embodiments, R 2C It is -S(O)2NR2. In some embodiments, R 2C It is -S(O)2F. In some embodiments, R 2C For -S(O)R. In some embodiments, R 2C For -S(O)NR2. In some embodiments, R 2C For -S(O)(NR)R. In some embodiments, R 2C For -C(O)R. In some embodiments, R 2C For -C(O)OR. In some embodiments, R 2C For -C(O)NR2. In some embodiments, R 2C For -C(O)N(R)OR. In some embodiments, R 2C For -OC(O)R. In some embodiments, R 2C For -OC(O)NR2. In some embodiments, R 2C It is -N(R)C(O)OR. In some embodiments, R 2C It is -N(R)C(O)R. In some embodiments, R 2C It is -N(R)C(O)NR2. In some embodiments, R 2C For example, -N(R)C(NR)NR2. In some embodiments, R 2C It is -N(R)S(O)2NR2. In some embodiments, R 2C It is -N(R)S(O)2R. In some embodiments, R 2C For -P(O)R2. In some embodiments, R 2C For -P(O)(R)OR. In some embodiments, R 2C It is -B(OR)2.

[0498] In some embodiments, R 2CEach instance 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.

[0499] In some embodiments, R 2C Each instance is independently halogenated, -CN, or -NO2. In some embodiments, R 2C Each instance is independently -OR, -SR, or -NR2. In some embodiments, R 2C Each instance 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, R 2C Each instance is independently -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, R 2C Each instance is independently -OC(O)R or -OC(O)NR2. In some embodiments, R 2C Each instance 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 2C Each instance is independently -P(O)R2 or -P(O)(R)OR.

[0500] In some embodiments, R 2C Each instance is independently -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R 2C Each instance 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 instance 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.

[0501] In some embodiments, R 2C Each instance is independently -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R 2C Each instance is independently -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 2C Each instance is independently -SR, -S(O)2R, or -S(O)R. In some embodiments, R 2C Each instance is independently -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R 2C Each instance is independently -S(O)2NR2 or -S(O)NR2. In some embodiments, R 2C Each instance is independently -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0502] In some embodiments, R 2C Each instance is independently -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R 2C Each instance is independently -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R 2C Each instance is independently -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R 2C Each instance is independently -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R 2C Each instance is independently -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0503] In some embodiments, R 2C Each instance is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R 2C Each instance is independently -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R 2C Each instance is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0504] In some embodiments, R 2C Each instance is independently a C that can be arbitrarily replaced. 1-6 Aliphatic group. In some embodiments, R 2CEach instance is independently a optionally substituted phenyl group. In some embodiments, R 2C Each instance is independently a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having one or two independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 2C Each instance is independently a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur.

[0505] In some embodiments, R 2C Each instance is independently a C that can be arbitrarily replaced. 1-6 An aliphatic group or an optionally substituted 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having one or two independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R 2C Each example is independently a 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.

[0506] In some embodiments, R 2C Each instance is independently a C that can be arbitrarily replaced. 1-6 Aliphatic group or optionally substituted phenyl group. In some embodiments, R 2C Each instance 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.

[0507] In some embodiments, R 2C Each example is independently selected from the following optionally substituted groups: phenyl, 3 to 7 membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6 membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0508] In some embodiments, R 2C Each instance is independently C 1-6 Aliphatic group. In some embodiments, R 2C It is phenyl. In some embodiments, R 2C Each instance 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. In some embodiments, R 2C Each instance is independently a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0509] In some embodiments, R 2C Each instance is independently C1-6 An aliphatic group or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 2C Each instance is independently a phenyl or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0510] In some embodiments, R 2C Each instance is independently C 1-6 Aliphatic group or phenyl. In some embodiments, R 2C Each instance 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.

[0511] In some embodiments, R 2C Each example is independently a phenyl ring, 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.

[0512] In some embodiments, R 2C Each instance is independently a halogen, -CN, -O- (optionally substituted C). 1-6 (Aliphatic group) or optionally substituted C 1-6 Aliphatic group. In some embodiments, R 2C Each instance is independently a halogen, -CN, -O-(C 1-6 (Aliphatic group) or C 1-6 Aliphatic groups; where each C 1-6 The aliphatic group is optionally substituted with one or more halogen atoms. In some embodiments, R 2C Each instance is independently a halogen or optionally a C substituted with one to three halogens. 1-3 Aliphatic group. In some embodiments, R 2C Each instance is independently fluorine, chlorine, -CH3, -CHF2, or -CF3.

[0513] In some embodiments, R 2CEach instance is independently an oxo group, 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 groups.

[0514] In some embodiments, R 2C Each example is independently selected from the groups described in the compounds in Table 1.

[0515] As generally defined above, R EC Each instance is independently an oxo group, 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 an optionally substituted group selected from the following: C 1-6 Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0516] In some embodiments, R ECEach instance is independently an oxo group, 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, or -B(OR)2. In some embodiments, R EC Each instance is independently an oxo group, deuterium, halogen, -CN, -NO2, -OR, -NR2, -C(O)R, -C(O)OR, -C(O)NR2, -OC(O)R, -N(R)C(O)R, or -N(R)S(O)2R. In some embodiments, R EC Each instance is independently deuterium, halogen, -CN-, -OR, or -NR2. In some embodiments, R EC Each instance is independently either deuterium or halogen. In some embodiments, R EC Each instance is independently a halogen.

[0517] In some embodiments, R EC Each instance is independently selected from the following substituted groups: C 1-6 Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0518] In some embodiments, R EC Each example is independently selected from the groups described in the compounds in Table 1.

[0519] As generally defined above, R QCEach instance is independently an oxo group, 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 an optionally substituted group selected from the following: C 1-6 Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0520] In some embodiments, R QC Each instance is independently an oxo group, 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 an optionally substituted group selected from the following: C 1-6 Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0521] In some embodiments, R QCEach instance is independently an oxo group, 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 QC Each instance is independently selected from the following substituted groups: C 1-6 Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0522] In some embodiments, R QC For oxidation. In some embodiments, R... QC For deuterium. In some embodiments, R QC Each instance is independently a halogen. In some embodiments, R QC For -CN. In some embodiments, R QC For -NO2. In some embodiments, R QC For -OR. In some embodiments, R QC For -SR. In some embodiments, R QC For -NR2. In some embodiments, R QC For -S(O)2R. In some embodiments, R QC It is -S(O)2NR2. In some embodiments, R QC It is -S(O)2F. In some embodiments, R QC For -S(O)R. In some embodiments, R QC For -S(O)NR2. In some embodiments, R QC For -S(O)(NR)R. In some embodiments, R QC For -C(O)R. In some embodiments, R QC For -C(O)OR. In some embodiments, R QC For -C(O)NR2. In some embodiments, R QC For -C(O)N(R)OR. In some embodiments, R QC For -OC(O)R. In some embodiments, R QCFor -OC(O)NR2. In some embodiments, R QC It is -N(R)C(O)OR. In some embodiments, R QC It is -N(R)C(O)R. In some embodiments, R QC It is -N(R)C(O)NR2. In some embodiments, R QC For example, -N(R)C(NR)NR2. In some embodiments, R QC It is -N(R)S(O)2NR2. In some embodiments, R QC It is -N(R)S(O)2R. In some embodiments, R QC For -P(O)R2. In some embodiments, R QC For -P(O)(R)OR. In some embodiments, R QC It is -B(OR)2.

[0523] In some embodiments, R QC Each instance 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.

[0524] In some embodiments, R QC Each instance is independently halogenated, -CN, or -NO2. In some embodiments, R QC Each instance is independently -OR, -SR, or -NR2. In some embodiments, R QC Each instance 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, R QC Each instance is independently -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, R QC Each instance is independently -OC(O)R or -OC(O)NR2. In some embodiments, R QCEach instance 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 QC Each instance is independently -P(O)R2 or -P(O)(R)OR.

[0525] In some embodiments, R QC Each instance is independently -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R QC Each instance 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 QC Each instance 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.

[0526] In some embodiments, R QC Each instance is independently -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R QC Each instance is independently -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R QC Each instance is independently -SR, -S(O)2R, or -S(O)R. In some embodiments, R QC Each instance is independently -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R QC Each instance is independently -S(O)2NR2 or -S(O)NR2. In some embodiments, R QC Each instance is independently -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0527] In some embodiments, R QC Each instance is independently -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R QC Each instance is independently -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R QC Each instance is independently -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R QCEach instance is independently -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R QC Each instance is independently -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0528] In some embodiments, R QC Each instance is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R QC Each instance is independently -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R QC Each instance is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0529] In some embodiments, R QC Each instance is independently a C that can be arbitrarily replaced. 1-6 Aliphatic group. In some embodiments, R QC Each instance is independently a optionally substituted phenyl group. In some embodiments, R QC Each instance is independently a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having one or two independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R QC Each instance is independently a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur.

[0530] In some embodiments, R QC Each instance is independently a C that can be arbitrarily replaced. 1-6 An aliphatic group or an optionally substituted 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having one or two independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R QC Each example is independently a 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.

[0531] In some embodiments, R QC Each instance is independently a C that can be arbitrarily replaced. 1-6 Aliphatic group or optionally substituted phenyl group. In some embodiments, R QC Each instance 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.

[0532] In some embodiments, R QC Each example is independently selected from the following optionally substituted groups: phenyl, 3 to 7 membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6 membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0533] In some embodiments, R QC Each instance is independently C 1-6 Aliphatic group. In some embodiments, R QC It is phenyl. In some embodiments, R QC Each instance 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. In some embodiments, R QC Each instance is independently a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0534] In some embodiments, R QC Each instance is independently C 1-6 An aliphatic group or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R QC Each instance is independently a phenyl or a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0535] In some embodiments, R QC Each instance is independently C 1-6 Aliphatic group or phenyl. In some embodiments, R QC Each instance 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.

[0536] In some embodiments, R QC Each example is independently a phenyl ring, 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.

[0537] In some embodiments, R QC Each example is independently selected from the groups described in the compounds in Table 1.

[0538] As generally defined above, R XCEach instance is independently an oxo group, 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 an optionally substituted group selected from the following: C 1-6 Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0539] In some embodiments, R XC Each instance is independently an oxo group, 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 an optionally substituted group selected from the following: C 1-6 Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0540] In some embodiments, R XCEach instance is independently an oxo group, 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 XC Each instance is independently selected from the following substituted groups: C 1-6 Aliphatic groups, phenyl groups, 3 to 7-membered saturated or partially unsaturated monocyclic heterocycles having 1 to 2 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5 to 6-membered monocyclic heteroaryl rings having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0541] In some embodiments, R XC For oxidation. In some embodiments, R... XC For deuterium. In some embodiments, R XC Each instance is independently a halogen. In some embodiments, R XC For -CN. In some embodiments, R XC For -NO2. In some embodiments, R XC For -OR. In some embodiments, R XC For -SR. In some embodiments, R XC For -NR2. In some embodiments, R XC For -S(O)2R. In some embodiments, R XC It is -S(O)2NR2. In some embodiments, R XC It is -S(O)2F. In some embodiments, R XC For -S(O)R. In some embodiments, R XC For -S(O)NR2. In some embodiments, R XC For -S(O)(NR)R. In some embodiments, R XC For -C(O)R. In some embodiments, R XC For -C(O)OR. In some embodiments, R XC For -C(O)NR2. In some embodiments, R XC For -C(O)N(R)OR. In some embodiments, R XC For -OC(O)R. In some embodiments, R XCFor -OC(O)NR2. In some embodiments, R XC It is -N(R)C(O)OR. In some embodiments, R XC It is -N(R)C(O)R. In some embodiments, R XC It is -N(R)C(O)NR2. In some embodiments, R XC For example, -N(R)C(NR)NR2. In some embodiments, R XC It is -N(R)S(O)2NR2. In some embodiments, R XC It is -N(R)S(O)2R. In some embodiments, R XC For -P(O)R2. In some embodiments, R XC For -P(O)(R)OR. In some embodiments, R XC It is -B(OR)2.

[0542] In some embodiments, R XC Each instance 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.

[0543] In some embodiments, R XC Each instance is independently halogenated, -CN, or -NO2. In some embodiments, R XC Each instance is independently -OR, -SR, or -NR2. In some embodiments, R XC Each instance 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, R XC Each instance is independently -C(O)R, -C(O)OR, -C(O)NR2, or -C(O)N(R)OR. In some embodiments, R XC Each instance is independently -OC(O)R or -OC(O)NR2. In some embodiments, R XCEach instance 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 XC Each instance is independently -P(O)R2 or -P(O)(R)OR.

[0544] In some embodiments, R XC Each instance is independently -OR, -OC(O)R, or -OC(O)NR2. In some embodiments, R XC Each instance 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 XC Each instance 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.

[0545] In some embodiments, R XC Each instance is independently -S(O)2R, -S(O)2NR2, or -S(O)2F. In some embodiments, R XC Each instance is independently -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R XC Each instance is independently -SR, -S(O)2R, or -S(O)R. In some embodiments, R XC Each instance is independently -S(O)2NR2, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R XC Each instance is independently -S(O)2NR2 or -S(O)NR2. In some embodiments, R XC Each instance is independently -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0546] In some embodiments, R XC Each instance is independently -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R XC Each instance is independently -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R XC Each instance is independently -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R XCEach instance is independently -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R XC Each instance is independently -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0547] In some embodiments, R XC Each instance is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R, or -N(R)C(O)NR2. In some embodiments, R XC Each instance is independently -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R XC Each instance is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0548] In some embodiments, R XC Each instance is independently a C that can be arbitrarily replaced. 1-6 Aliphatic group. In some embodiments, R XC Each instance is independently a optionally substituted phenyl group. In some embodiments, R XC Each instance is independently a 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having one or two independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R XC Each instance is independently a 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur.

[0549] In some embodiments, R XC Each instance is independently a C that can be arbitrarily replaced. 1-6 An aliphatic group or an optionally substituted 3- to 7-membered saturated or partially unsaturated monocyclic heterocycle having one or two independently selected heteroatoms chosen from nitrogen, oxygen, and sulfur. In some embodiments, R XC Each example is independently a substituted phenyl or an optionally substituted 5- to 6-membered monocyclic heteroaryl ring having 1 to 4 heteroat...

Claims

1. A compound which is or a pharmaceutically acceptable salt thereof.

2. A compound which is or a pharmaceutically acceptable salt thereof.

3. A compound which is or a pharmaceutically acceptable salt thereof.

4. A pharmaceutical composition comprising a compound: or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

5. A pharmaceutical composition comprising a compound: or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

6. A pharmaceutical composition comprising a compound: or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

7. Use of a pharmaceutical composition comprising a compound: or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, for the manufacture of a medicament for inhibiting PI3K a signaling activity in a subject in need thereof.

8. Use of a pharmaceutical composition comprising a compound: or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, for the manufacture of a medicament for inhibiting PI3K a signaling activity in a subject in need thereof.

9. Use of a pharmaceutical composition comprising a compound: or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, for the manufacture of a medicament for inhibiting PI3K a signaling activity in a subject in need thereof.

10. Use of a pharmaceutical composition comprising a compound: or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, for the manufacture of a medicament for treating a PI3K a mediated disorder in a subject in need thereof.

11. Use of a pharmaceutical composition comprising a compound: or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, for the manufacture of a medicament for treating a PI3K a mediated disorder in a subject in need thereof.

12. Use of a pharmaceutical composition comprising a compound: or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, for the manufacture of a medicament for treating a PI3K a mediated disorder in a subject in need thereof.

13. Use of a pharmaceutical composition comprising a compound: or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, for the manufacture of a medicament for treating a cell proliferative disease in a subject in need thereof.

14. Use of a pharmaceutical composition comprising a compound: or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, for the manufacture of a medicament for treating a cell proliferative disease in a subject in need thereof.

15. Use of a pharmaceutical composition comprising a compound: or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, for the manufacture of a medicament for treating a cell proliferative disease in a subject in need thereof.

16. The use according to claims 13-15, wherein the cell proliferative disease is cancer.

17. The use according to any one of claims 7 to 15, wherein the subject has a PI3K a containing at least one of the following mutations: H1047R, E542K and E545K.

18. The composition according to any one of claims 4 to 6, wherein the carrier is an adjuvant or vehicle. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ 19. The use according to any one of claims 7 to 15, wherein the vehicle is an adjuvant or vehicle.

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