PI3Kalpha inhibitors and methods of use thereof

Abstract

The present disclosure relates to novel compounds and pharmaceutical compositions thereof and methods of inhibiting the activity of the PI3K alpha enzyme with the compounds and compositions of the present disclosure. The present disclosure also relates to, but is not limited to, methods of treating conditions associated with PI3K alpha signaling with the compounds and compositions of the present disclosure.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 364,459, filed May 10, 2022, which is hereby incorporated by reference in its entirety. Background Art

[0003] Phosphatidylinositol 3-kinases (PI3Ks) comprise a family of lipid kinases that catalyze the transfer of phosphates to the D-3′ position of inositol lipids to generate phosphoinositide-3-phosphate (PIP), phosphoinositide-3,4-bisphosphate (PIP2), and phosphoinositide-3,4,5-triphosphate (PIP3), which in turn serve as second messengers in signaling cascades by docking proteins containing pleckstrin-homology, FYVE, Phox, and other phospholipid-binding domains into a variety of signaling complexes, typically at the plasma membrane (Vanhaesebroeck et al., Annu. Rev. Biochem 70:535 (2001); Katso et al., Annu. Rev. Cell Dev. Biol. 17:615 (2001)). Of the two Class 1 PI3K subclasses, Class 1A PI3Ks are heterodimers composed of a catalytic p110 subunit (α, β, or δ isoform) constitutively associated with a regulatory subunit, which can be p85α, p55α, p50α, p85β, or p55γ. The Class 1B subclass has one family member that is a heterodimer composed of a catalytic p110γ subunit associated with one of two regulatory subunits, p101 or p84 (Fruman et al., Annu. Rev. Biol. 67:481 (1998); Suire et al., Curr. Biol. 15:566 (2005)). The modular domain structure of the p85 / 55 / 50 subunits includes an Src homology (SH2) domain that binds to phosphotyrosine residues on activating receptors and cytoplasmic tyrosine kinases in a specific sequence context, leading to the activation and localization of class 1A PI3Ks. Class 1B PI3Ks are directly activated by G protein-coupled receptors that bind a diverse repertoire of peptide and non-peptide ligands (Stephens et al., Cell 89:105 (1997); Cassel et al., Annu. Rev. Cell Dev. Biol. 17:615-675 (2001)).

[0004] Thus, the resulting phospholipid products of class I PI3Ks link upstream receptors to downstream cellular activities including proliferation, survival, chemotaxis, cell migration, motility, metabolism, inflammatory and allergic responses, transcription, and translation (Cantley et al., Cell 64:281 (1991); Escobedo and Williams, Nature 335:85 (1988); Fantl et al., Cell 69:413 (1992)). In many cases, PIP2 and PIP3 recruit Aid, the product of the human homolog of the viral oncogene v-Akt, to the plasma membrane where it serves as a node for numerous intracellular signaling pathways that are critical for growth and survival (Van ter et al., Cell 69:413-423 (1992); Bader et al., Nature Rev. Cancer 5:921 (2005); Vivanco and Sawyer, Nature Rev. Cancer 2:489 (2002)).

[0005] Aberrant regulation of PI3K, often through Aid activation, increases survival and is one of the most common events in human cancers, and has been shown to occur at multiple levels. The tumor suppressor gene PTEN is functionally deleted in many tumors. PTEN dephosphorylates phosphoinositides at the 3′ position of the inositol ring and thereby antagonizes PI3K activity. In other tumors, the genes for the p110α isoform PIK3CA and Akt are amplified, and several human cancers demonstrate increased protein expression of their gene products. Furthermore, mutations and translocations of p85α, which upregulate the p85-p110 complex, have been described in human cancers. Finally, somatic missense mutations in PIK3CA are frequently described in a variety of human cancers, which activate 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 indicate that dysregulation of phosphoinositide-3 kinase and upstream and downstream components of this signaling pathway is one of the most common disorders associated with human cancer and proliferative diseases (Parsons et al., Nature 436:792 (2005); Hennessey et al., Nature Rev. Drug Disc. 4:988-1004 (2005)).

[0006] In view of the above, PI3Kα inhibitors will be of particular value in the treatment of proliferative diseases and other conditions. Although a variety of PI3K inhibitors have been developed (such as taselisib, alpelisib, buparlisib, etc.), these molecules inhibit multiple Class 1A PI3K isoforms. Inhibitors that are active against multiple Class 1A PI3K isoforms are called "pan-PI3K" inhibitors. A major obstacle to the clinical development of existing PI3K inhibitors is the inability to achieve the desired target inhibition level 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 characteristics. Inhibition of PI3Kα is associated with hyperglycemia and rash, whereas inhibition of PI3Kδ or PI3Kγ is associated with diarrhea, myelosuppression, and elevated transaminases (Hanker et al., Cancer Discovery (2019) PMID: 30837161). Therefore, selective PI3Kα inhibitors may increase the therapeutic window, enabling adequate target inhibition in tumors while avoiding dose-limiting toxicities in cancer patients. Summary of the Invention

[0007] In some embodiments, the present disclosure provides a compound of Formula I:

[0008]

[0009] or a pharmaceutically acceptable salt thereof, wherein Cy 1 、Cy 2 , Q, and T are each as defined in the Examples and classes and subclasses herein.

[0010] In some embodiments, the present disclosure provides a pharmaceutical composition comprising a compound of Formula I or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or diluent.

[0011] In some embodiments, the present disclosure provides a method of treating a PI3Kα-mediated disorder comprising administering to a patient in need thereof a compound of Formula I or a composition comprising the compound.

[0012] In some embodiments, the present disclosure provides a method for providing a compound of Formula I or a synthetic intermediate thereof.

[0013] In some embodiments, the present disclosure provides a method for providing a pharmaceutical composition comprising a compound of Formula I. DETAILED DESCRIPTION

[0014] 1. General description of certain embodiments of the present disclosure:

[0015] The compounds of the present disclosure and their pharmaceutical compositions can be used as PI3Kα inhibitors. In some embodiments, the present disclosure provides a compound of formula I:

[0016]

[0017] or a pharmaceutically acceptable salt thereof, wherein:

[0018] Cy 1 is phenyl; naphthyl; cubanyl; adamantyl; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein Cy 1 By n R 1 replace;

[0019] Cy 2 is phenyl; naphthyl; cubanyl; adamantyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein Cy 2 By m R 2 replace;

[0020] Q is for L Q ;

[0021] T is q R T Substituted divalent C 1-3 aliphatic chains;

[0022] Each R 1 Independently -L 1 -R 1A ;

[0023] Each R 2 Independently -L 2 -R 2A ;

[0024] Each R T Independently -L T -R TAor

[0025] Two R's T Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 1 R TTC replace;

[0026] Two R's 1 Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 2 R 11C replace;

[0027] Two R's 2 Together with its intervening atoms, it forms a 3-7 membered saturated, partially unsaturated or aromatic carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 3 R 22C replace;

[0028] One R T With an R 1 Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 4 R T1C replace; or

[0029] One R T With an R L Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 5 R TLC replace;

[0030] L 1 、L 2 、L Q and L T Each independently is a covalent bond or C 1-4 A divalent saturated or unsaturated, linear or branched hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6 Alkylene, C 3-6heteroalkylene, -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-;

[0031] Each R 1A Independently 1 R 1C Replaced R A or R B ;

[0032] Each R 2A Independently 2 R 2C Replaced R A or R B ;

[0033] Each R TA Independently 3 R TC Replaced R A or R B ;

[0034] Each R L Independently 4 R LC Replaced R A or R B ;

[0035] R A is independently at each occurrence oxo, deuterium, halogen, -CN, -NO2, -OR, -SF5, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -S(O)(NCN)R, -S(NCN)R, -C(O)R, -C(O)OR, -C(O )NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)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;

[0036] R B In each case, independently C 1-6aliphatic chain; phenyl; naphthyl; cubanyl; adamantyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocycle; a 5-12 membered saturated or partially unsaturated bicyclic carbocycle; a 3-7 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0037] R 1C 、R 2C 、R TC 、R TTC 、R 11C 、R 22C 、R T1C 、R TLC and R LC wherein each occurrence is independently oxo, deuterium, halogen, —CN, —NO, —OR, —SF, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0038] R is independently hydrogen at each occurrence or an optionally substituted group selected from the group consisting of: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or

[0039] The two R groups on the same nitrogen atom, together with their intervening atoms, form a 4-7 membered saturated, partially unsaturated or heteroaryl ring having, in addition to nitrogen, 0-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; and

[0040] n, m, q, p1 、p 2 、p 3 、p 4 、p 5 、r 1 、r 2 、r 3 and r 4 Each independently is 0, 1, 2, 3, 4 or 5.

[0041] 2. Compounds and Definitions

[0042] The compounds of the present disclosure include those generally described herein and are further described by the classes, subclasses, and species disclosed herein. Unless otherwise indicated, as used herein, the following definitions shall apply. For the purposes of this disclosure, chemical elements are identified according to the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th edition. In addition, the general principles of organic chemistry are described in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausalito: 1999; and "March's Advanced Organic Chemistry", 5th edition, eds. Smith, MB and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are incorporated herein by reference.

[0043] As used herein, the term "aliphatic" or "aliphatic group" means a straight (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain that is fully saturated or contains one or more unsaturated units, or a monocyclic or bicyclic hydrocarbon (also referred to herein as "carbocycle" or "cycloaliphatic") that is fully saturated or contains one or more unsaturated units but is not an aromatic group, which has a single point of attachment to the rest of the molecule. Unless otherwise specified, an aliphatic group contains 1-6 aliphatic carbon atoms. In some embodiments, an aliphatic group contains 1-5 aliphatic carbon atoms. In other embodiments, an aliphatic group contains 1-4 aliphatic carbon atoms. In yet other embodiments, an aliphatic group contains 1-3 aliphatic carbon atoms, and in yet other embodiments, an aliphatic group contains 1-2 aliphatic carbon atoms. In some embodiments, a "cycloaliphatic group" (or "carbocycle") refers to a monocyclic C3-C6 hydrocarbon that is fully saturated or contains one or more unsaturated units but is not an aromatic group, which has a single point of attachment to the rest of the molecule. Suitable aliphatic groups include, but are not limited to, linear or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl groups, and mixtures thereof, such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl, or (cycloalkyl)alkenyl.

[0044] As used herein, unless otherwise indicated, the term "alkyl" refers to a monovalent aliphatic hydrocarbon radical having a linear, branched, monocyclic or polycyclic moiety, or a combination thereof, wherein the radical is optionally substituted at one or more carbons of the linear, branched, monocyclic or polycyclic moiety, or a combination thereof, with one or more substituents at each carbon, wherein the one or more substituents are independently C1-C 10 Examples of "alkyl" include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl, and the like.

[0045] The term "lower alkyl" refers to C 1-4 Straight-chain or branched alkyl groups. Exemplary lower alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl.

[0046] The term "lower haloalkyl" refers to a C 1-4 Straight-chain or branched-chain alkyl.

[0047] The term "heteroatom" means one or more of oxygen, sulfur, nitrogen, phosphorus, or silicon (including any oxidized form of nitrogen, sulfur, phosphorus, or silicon; a quaternized form of any basic nitrogen; or a substitutable nitrogen of a heterocyclic ring, such as N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl), or NR + (as in N-substituted pyrrolidinyl)).

[0048] As used herein, the term "unsaturated" means that a moiety has one or more units of unsaturation.

[0049] As used herein, the term "C 1-8 (or C 1-6 or C 1-4 ) divalent saturated or unsaturated, straight or branched hydrocarbon chain" refers to straight or branched divalent alkylene, alkenylene and alkynylene chains as defined herein.

[0050] The term "alkylene" refers to a divalent alkyl group. An "alkylene chain" is a polymethylene group, i.e., -(CH2) n -, wherein n is a positive integer, preferably 1 to 6, 1 to 4, 1 to 3, 1 to 2 or 2 to 3. A substituted alkylene chain is a polymethylene chain in which one or more methylene hydrogen atoms are replaced by a substituent. Suitable substituents include those described below for substituted aliphatic groups.

[0051] The term "alkenylene" refers to a divalent alkenyl group. Substituted alkenylene chains are polymethylene groups containing at least one double bond and in which one or more hydrogen atoms are replaced by a substituent. Suitable substituents include those described below for substituted aliphatic groups.

[0052] The term "halogen" means F, Cl, Br or I.

[0053] The term "aryl," used alone or as part of a larger moiety such as "aralkyl," "aralkyloxy," or "aryloxyalkyl," refers to a monocyclic or bicyclic ring system having a total of five to fourteen ring members, wherein at least one ring in the system is aromatic, and wherein each ring in the system contains three to seven ring members. The term "aryl" is used interchangeably with the term "aryl ring." In certain embodiments of the present disclosure, "aryl" refers to an aromatic ring system including, but not limited to, phenyl, biphenyl, naphthyl, anthracenyl, and the like, which may carry one or more substituents.

[0054] Unless otherwise defined, as used herein, the term "heteroaryl" or "heteroaromatic" refers to a monocyclic aromatic 5-6 membered ring containing one or more heteroatoms, e.g., one to three heteroatoms, such as nitrogen, oxygen and sulfur; or an 8-10 membered polycyclic ring system containing one or more heteroatoms, wherein at least one ring in the polycyclic ring system is aromatic and the points of attachment of the polycyclic ring system are through ring atoms on the aromatic ring. A heteroaryl ring may be attached to an adjacent group through carbon or nitrogen. Examples of heteroaryl rings include, but are not limited to, furan, thiophene, pyrrole, thiazole, oxazole, isothiazole, isoxazole, imidazole, pyrazole, triazole, pyridine, pyrimidine, indole and the like. For example, unless otherwise defined, 1,2,3,4-tetrahydroquinoline is a heteroaryl ring when its point of attachment is through a benzo ring, e.g.:

[0055]

[0056] Unless otherwise defined, the term "heterocyclyl" or "heterocyclic group" refers to a saturated or partially unsaturated 3-10 membered monocyclic or 7-14 membered polycyclic ring system, including bridged or fused rings, and whose ring system includes one to four heteroatoms such as nitrogen, oxygen and sulfur. The heterocyclyl ring can be attached to the adjacent group through carbon or nitrogen.

[0057] Unless otherwise defined, the term "partially unsaturated" in the context of a ring refers to a monocyclic ring, or a constituent ring within a polycyclic (e.g., bicyclic, tricyclic, etc.) ring system, wherein the constituent ring contains at least one degree of unsaturation in addition to the unsaturation provided by the ring itself, but is not an aromatic ring. Examples of partially unsaturated rings include, but are not limited to, 3,4-dihydro-2H-pyran, 3-pyrroline, 2-thiazoline, and the like. Where a partially unsaturated ring is part of a polycyclic ring system, the other constituent rings in the polycyclic ring system may be saturated, partially unsaturated, or aromatic, but the point of attachment of the polycyclic ring system is on the partially unsaturated constituent ring. For example, unless otherwise defined, 1,2,3,4-tetrahydroquinoline is a partially unsaturated ring when its point of attachment is through an N-piperidinyl ring, for example:

[0058]

[0059] Unless otherwise defined, the term "saturated" refers to a 3-10 yuan monocyclic or 7-14 yuan polycyclic (e.g., bicyclic, tricyclic, etc.) ring system in the case of a ring, wherein the monocyclic or constituent ring as the connection point of the polycyclic ring system does not contain any other unsaturation except the unsaturation provided by the ring itself. The example of a monocyclic saturated ring includes but is not limited to azetidine, oxetane, cyclohexane, etc. In the case where a saturated ring is a part of a polycyclic ring system, the other constituent rings in the polycyclic ring system can be saturated, partially unsaturated or aromatic rings, but the connection point of the polycyclic ring system is on a saturated constituent ring. For example, unless otherwise defined, 2-azaspiro [3.4] oct-6-ene is a saturated ring when its connection point is through an N-azetidine ring, for example:

[0060]

[0061] As used herein, the terms "alkylene," "arylene," "cycloalkylene," "heteroarylene," "heterocycloalkylene," and other similar terms having the prefix "alkylene" refer to the divalent bonded form of the group modified by the prefix. For example, "alkylene" is a divalent alkyl group that links the group to which it is attached.

[0062] As used herein, the term "bridged bicyclic" refers to any saturated or partially unsaturated bicyclic system with at least one bridge bond, that is, carbocyclic or heterocyclic radical. According to IUPAC definition, a "bridge bond" is a non-branched chain or an atom or valence bond consisting of multiple atoms connecting two bridge heads, wherein a "bridge head" is any backbone atom bonded to a ring system of three or more backbone atoms (excluding hydrogen). In certain embodiments, the bridged bicyclic group has 7-12 ring members and 0-4 heteroatoms independently selected from nitrogen, oxygen and sulfur. Such bridged bicyclic groups are well known in the art and include the following groups stated, wherein each group is connected to the rest of the molecule at any substitutable carbon or nitrogen atom. Unless otherwise stated, the bridged bicyclic group is optionally substituted by one or more substituents as described for an aliphatic group. Additionally or alternatively, any substitutable nitrogen of the bridged bicyclic group is optionally substituted. Exemplary bridged bicyclic groups include:

[0063]

[0064] As described herein, the compounds of the present disclosure may contain "optionally substituted" moieties. In general, the term "substituted", whether or not preceded by the term "optionally", means that one or more hydrogens of the designated moiety are replaced by a suitable substituent. Unless otherwise indicated, an "optionally substituted" group may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure can be substituted by more than one substituent selected from a specified group, the substituent at each position may be the same or different. The combinations of substituents envisioned by the present disclosure are preferably substituents that form stable or chemically feasible compounds. As used herein, the term "stable" refers to a compound that does not substantially change when subjected to conditions that allow it to be manufactured, detected, and in certain embodiments, recovered, purified, and used for one or more purposes disclosed herein.

[0065] Suitable monovalent substituents on the substitutable carbon atoms of an "optionally substituted" group are independently halogen; -(CH2) 0-4 R ○ ; -(CH2) 0-4 OR ○ ;-O(CH2) 0-4 R ○ ;-O-(CH2) 0-4 C(O)OR ○ ; -(CH2) 0-4 CH(OR ○ )2;-(CH2) 0-4 SR ○ ; -(CH2) 0-4 Ph, which can be R ○ Substitution; -(CH2)0-4 O(CH2) 0-1 Ph, which can be R ○ Substituted; -CH=CHPh, which can be R ○ Substitution; -(CH2) 0-4 O(CH2) 0-1 -pyridyl, which may be R ○ Substitution; -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) 0-4 OC(O)R ○ ;-OC(O)(CH2) 0-4 SR ○ ;-SC(S)SR ○ ; -(CH2) 0-4 SC(O)R ○ ; -(CH2) 0-4 C(O)NR ○ 2;-C(S)NR ○ 2;-C(S)SR○ ;-SC(S)SR ○ ; -(CH2) 0-4 OC(O)NR ○ 2;-C(O)N(OR ○ )R ○ ;-C(O)C(O)R ○ ;-C(O)CH2C(O)R ○ ;-C(NOR ○ )R ○ ; -(CH2) 0-4 SSR ○ ; -(CH2) 0-4 S(O)2R ○ ; -(CH2) 0-4 S(O)2OR ○ ; -(CH2) 0-4 OS(O)2R ○ ;-S(O)2NR ○ 2; -(CH2) 0-4 S(O)R ○ ;-N(R ○ )S(O)2NR ○ 2;-N(R ○ )S(O)2R ○ ;-N(OR ○ )R ○ ;-C(NH)NR ○ 2;-P(O)(OR ○ )R ○ ;-P(O)R ○ 2;-OP(O)R ○ 2;-OP(O)(OR ○ )2;-SiR ○ 3;-(C 1-4 linear or branched alkylene)ON(R ○ )2; or -(C 1-4 linear or branched alkylene) C(O)ON(R ○ )2, where each R ○ may be substituted as defined below and are independently hydrogen, C 1-6 Aliphatic groups, -CH2Ph, -O(CH2) 0-1 Ph, -CH2-(5-6 membered heteroaryl ring), or a 5-6 membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, or notwithstanding the above definitions, two independent occurrences of R ○Together with its intervening atoms, it forms a 3-12 membered saturated, partially unsaturated or aryl monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, which may be substituted as defined below.

[0066] R ○ (or by two independent occurrences of R ○ Suitable monovalent substituents on the ring formed together with its intervening atoms are independently halogen, -(CH2) 0-2 R ● 、-(halogen R ● ), -(CH2) 0-2 OH, -(CH2) 0-2 OR ● 、-(CH2) 0-2 CH(OR ● )2;-O(halogen 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 linear or branched alkylene)C(O)OR ● or -SSR ● , where each R ● unsubstituted or, in the case of a "halo" group, substituted only with one or more halogens, and independently selected from C 1-4 Aliphatic groups, -CH2Ph, -O(CH2) 0-1 Ph or a 5-6 membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur. ○ Suitable divalent substituents on a saturated carbon atom of include =0 and =S.

[0067] Suitable divalent substituents on a saturated carbon atom of an "optionally substituted" group include the following: =0, =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 * at each independent occurrence selected from hydrogen, C which may be substituted as defined below 1-6 aliphatic, or an unsubstituted 5-6 membered saturated, partially unsaturated or aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur. Suitable divalent substituents attached to the ortho-substitutable carbon of an "optionally substituted" group include: -O(CR * 2) 2-3 O-, where R * at each independent occurrence selected from hydrogen, C which may be substituted as defined below 1-6 aliphatic, or an unsubstituted 5-6 membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0068] R * Suitable substituents on the aliphatic group include halogen, -R ● 、-(halogen R ● ), -OH, -OR ● 、-O(halogen R ● )、-CN、-C(O)OH、-C(O)OR ● 、-NH2、-NHR ● 、-NR ● 2 or -NO2, where each R ● unsubstituted or, when preceded by "halo", substituted only by one or more halogens, and independently C 1-4 Aliphatic groups, -CH2Ph, -O(CH2) 0-1 Ph or a 5-6 membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0069] Suitable substituents on a substitutable nitrogen of an "optionally substituted" group include Each of these is independently hydrogen, which may be substituted as defined below 1-6 aliphatic, unsubstituted -OPh, or an unsubstituted 5-6 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or notwithstanding the above definitions, two independent occurrences of Together with its intervening atoms, it forms an unsubstituted 3-12 saturated, partially unsaturated or aromatic monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0070] Suitable substituents on the aliphatic group of are independently halogen, -R ● 、-(halogen R ● ), -OH, -OR ● 、-O(halogen R ● )、-CN、-C(O)OH、-C(O)OR ● 、-NH2、-NHR ● 、-NR ● 2 or -NO2, where each R ● unsubstituted or, when preceded by "halo", substituted only by one or more halogens, and independently C 1-4 Aliphatic groups, -CH2Ph, -O(CH2) 0-1 Ph or a 5-6 membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0071] 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 isomeric molecules having the same molecular formula but different arrangements of atoms and / or functional groups in space. All stereoisomers of the compounds of the present invention (e.g., stereoisomers that may exist due to asymmetric carbons on various substituents), including enantiomeric and diastereomeric forms, are encompassed 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 configurational) isomers, are within the scope of this disclosure.

[0072] As used herein, the term "tautomer" refers to one of two or more structural isomers that exist in equilibrium and are easily converted from one isomeric form to another isomeric form. It should be understood that tautomers encompass valence tautomers and proton tautomers (also known as prototropic tautomers). Valence tautomers include interconversions by reorganization of some bonded electrons. Proton tautomers include interconversions via proton migration, such as keto-enol and imine-enamine isomerizations. Unless otherwise stated, all tautomers of the compounds of the present disclosure are within the scope of the present disclosure.

[0073] As used herein, the term "isotopic substitution" refers to the replacement of an atom by its isotope. As used herein, the term "isotope" refers to an atom having the same atomic number as the atom that predominates in nature but a different mass number (number of neutrons) than the mass number of the atom that predominates in nature. It should be understood that a compound having isotopic substitution refers to a compound in which at least one atom contained in the compound is replaced by its isotope. Atoms that can be replaced by their isotopes include, but are not limited to, hydrogen, carbon, and oxygen. Examples of isotopes of hydrogen atoms include 2 H (also denoted as D) and 3 H. Examples of isotopes of carbon atoms include 13 C and 14 C. Examples of isotopes of oxygen atoms include 18 Unless otherwise stated, all isotopic substitutions of the compounds of the present disclosure are within the scope of the present disclosure. These compounds are useful, for example, as analytical tools, as probes in biological assays, or as therapeutic agents according to the present disclosure.

[0074] As used herein, the term "pharmaceutically acceptable salts" refers to salts that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, and commensurate with a reasonable benefit / risk ratio. Exemplary pharmaceutically acceptable salts are found, for example, in Berge et al. (J. Pharm. Sci. 1977, 66(1), 1; and Gould, PL, Int. J. Pharmaceutics 1986, 33, 201-217; (each of which is hereby incorporated by reference in its entirety).

[0075] Pharmaceutically acceptable salts of the compounds of the present disclosure include salts derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable non-toxic acid addition salts are salts formed of an amino group with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid, or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid, or by using other methods used in the art, such as salts formed by ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, and the like.

[0076] Salts derived from appropriate bases include alkali metal salts, alkaline earth metal salts, ammonium salts and N + (C 1-4 Representative alkali metal or alkaline earth metal salts include sodium salts, lithium salts, potassium salts, calcium salts, magnesium salts, and the like. Where appropriate, other pharmaceutically acceptable salts include non-toxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkyl sulfonates, and aryl sulfonates.

[0077] Pharmaceutically acceptable salts are also intended to encompass hemi-salts, wherein the ratio of compound:acid is 2:1, respectively. Exemplary hemi-salts are salts derived from acids containing two carboxylic acid groups, such as malic acid, fumaric acid, maleic acid, succinic acid, tartaric acid, glutaric acid, oxalic acid, adipic acid, and citric acid. Other exemplary hemi-salts are salts derived from diprotic mineral acids such as sulfuric acid. Exemplary preferred hemi-salts include, but are not limited to, hemimaleate, hemifumarate, and hemisuccinate.

[0078] As used herein, the term "about" is used herein to mean approximately, roughly, around, or in the neighborhood of. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values ​​recited. Generally, the term "about" is used herein to modify a numerical value above and below the recited value by 20% (higher or lower).

[0079] As used herein, an "effective amount," "sufficient amount," or "therapeutically effective amount" is an amount of a compound sufficient to achieve a beneficial or desired result, including a clinical result. Thus, an effective amount can be sufficient, for example, to reduce or ameliorate the severity and / or duration of a condition or one or more symptoms thereof associated with PI3Kα signaling; to prevent the progression of a condition or symptom associated with a condition associated with PI3Kα signaling; or to enhance or otherwise improve the prophylactic or therapeutic effect of another therapy. An effective amount also includes an amount of a compound that avoids or substantially reduces undesirable side effects.

[0080] As used herein, and as understood in the art, "treatment" is a method for obtaining beneficial or desired results (including clinical results). Beneficial or desired clinical results may include, but are not limited to, alleviation or improvement of one or more symptoms or conditions; reduction in the extent of the disease or ailment; stabilization of the state of the disease or ailment (i.e., no worsening); prevention of the spread of the disease or ailment; delay or slowing of the progression of the disease or ailment; improvement or alleviation of the disease or ailment state, and relief (partial or complete relief), whether detectable or undetectable. "Treatment" may also mean extending survival compared to the expected survival when not receiving treatment. In some embodiments, treatment may be administered after developing one or more symptoms. In other embodiments, treatment may be administered when asymptomatic. For example, treatment may be administered to susceptible individuals (e.g., based on a history of symptoms and / or based on genetic or other predisposing factors) before the onset of symptoms. Treatment may also be continued after the symptoms subside, for example to prevent or delay their recurrence.

[0081] The phrase "in need thereof" refers to a need for symptomatic or asymptomatic relief of a condition associated with PI3Kα signaling activity, or which may otherwise be alleviated by the compounds and / or compositions of the present disclosure.

[0082] 3. Description of Exemplary Embodiments

[0083] As described above, in some embodiments, the present disclosure provides a compound of Formula I:

[0084]

[0085] or a pharmaceutically acceptable salt thereof, wherein:

[0086] Cy 1is phenyl; naphthyl; cubanyl; adamantyl; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein Cy 1 By n R 1 replace;

[0087] Cy 2 is phenyl; naphthyl; cubanyl; adamantyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein Cy 2 By m R 2 replace;

[0088] Q is for L Q ;

[0089] T is q R T Substituted divalent C 1-3 aliphatic chains;

[0090] Each R 1 Independently -L 1 -R 1A ;

[0091] Each R 2 Independently -L 2 -R 2A ;

[0092] Each R T Independently -L T -R TA ;or

[0093] Two R's T Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 1 R TTC replace;

[0094] Two R's 1Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 2 R 11C replace;

[0095] Two R's 2 Together with its intervening atoms, it forms a 3-7 membered saturated, partially unsaturated or aromatic carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 3 R 22C replace;

[0096] One R T With an R 1 Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 4 R T1C replace; or

[0097] One R T With an R L Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 5 R TLC replace;

[0098] L 1 、L 2 、L Q and L T Each independently is a covalent bond, or C 1-4 A divalent saturated or unsaturated linear or branched hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 heterocycloalkylene, -N(R)-, -N(R)C(O)-, -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-;

[0099] Each R 1A Independently1 R 1C Replaced R A or R B ;

[0100] Each R 2A Independently 2 R 2C Replaced R A or R B ;

[0101] Each R TA Independently 3 R TC Replaced R A or R B ;

[0102] Each R L Independently 4 R LC Replaced R A or R B ;

[0103] R A is independently at each occurrence oxo, deuterium, halogen, -CN, -NO2, -OR, -SF5, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -S(O)(NCN)R, -S(NCN)R, -C(O)R, -C(O)OR, -C(O )NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)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;

[0104] R B In each case, independently C 1-6 aliphatic chain; phenyl; naphthyl; cubanyl; adamantyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocycle; a 5-12 membered saturated or partially unsaturated bicyclic carbocycle; a 3-7 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0105] R1C 、R 2C 、R TC 、R TTC 、R 11C 、R 22C 、R T1C 、R TLC and R LC wherein each occurrence is independently oxo, deuterium, halogen, —CN, —NO, —OR, —SF, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0106] R is independently hydrogen at each occurrence or an optionally substituted group selected from the group consisting of: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or

[0107] The two R groups on the same nitrogen atom, together with their intervening atoms, form a 4-7 membered saturated, partially unsaturated or heteroaryl ring having, in addition to nitrogen, 0-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; and

[0108] n, m, q, p 1 、p 2 、p 3 、p 4 、p 5 、r 1 、r 2 、r 3 and r 4 Each independently is 0, 1, 2, 3, 4 or 5.

[0109] As generally defined above, Cy 1is phenyl; naphthyl; cubanyl; adamantyl; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein Cy 1 By n R 1 replace.

[0110] In some embodiments, Cy 1 Is phenyl, where Cy 1 By n R 1 In some embodiments, Cy 1 is naphthyl, where Cy 1 By n R 1 In some embodiments, Cy 1 Is a cubic alkyl group, where Cy 1 By n R 1 In some embodiments, Cy 1 is adamantyl, where Cy 1 By n R 1 In some embodiments, Cy 1 is a 3-7 membered saturated or partially unsaturated monocyclic carbon ring, wherein Cy 1 By n R 1 In some embodiments, Cy 1 is a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 1 By n R 1 In some embodiments, Cy 1 is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 1 By n R 1 In some embodiments, Cy 1 is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 1 By n R 1 replace.

[0111] In some embodiments, Cy 1 yes where R 1 and n are as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1and n are as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 and n are as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 and n are as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 and n are as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 and n are as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 and n are as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 and n are as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 and n are as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 and n are as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 and n are as defined in the Examples and classes and subclasses herein.

[0112] In some embodiments, Cy 1 yes where R 1 is halogen and n is as defined in the Examples and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 In some embodiments, Cy 1 yes where R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 In some embodiments, Cy1 yes where R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 In some embodiments, Cy 1 yes where R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 In some embodiments, Cy 1 yes where R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 It's a halogen.

[0113] In some embodiments, Cy 1 yes where R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 In some embodiments, Cy 1 yes In some embodiments, Cy 1 yes

[0114] In some embodiments, Cy 1 yes where R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 In some embodiments, Cy 1 yes where R 1 In some embodiments, Cy 1 yes where R 1 In some embodiments, Cy 1 yes

[0115] In some embodiments, Cy 1 yes where R 1As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 In some embodiments, Cy 1 yes where R 1 In some embodiments, Cy 1 yes where R 1 In some embodiments, Cy 1 yes

[0116] In some embodiments, Cy 1 yes where R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 In some embodiments, Cy 1 yes where R 1 In some embodiments, Cy 1 yes where R 1 In some embodiments, Cy 1 yes

[0117] In some embodiments, Cy 1 yes where R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where R 1 As defined in the embodiments and classes and subclasses herein.

[0118] In some embodiments, Cy 1 is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein Cy 1 By n R 1 Substituted, where R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 is an 8-10 membered bicyclic heteroaryl ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein Cy 1 By n R 1 Substituted, where R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein.

[0119] In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 1 yes where n and R1 As defined in the embodiments and classes and subclasses herein.

[0120] In some embodiments, Cy 1 is a group selected from the compounds described in Table 1. In some embodiments, Cy 1 Not for

[0121] As generally defined above, Cy 2 is phenyl; naphthyl; cubanyl; adamantyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein Cy 2 By m R 2 replace.

[0122] In some embodiments, Cy 2 Is phenyl, where Cy 2 By m R 2 In some embodiments, Cy 2 is naphthyl, where Cy 2 By m R 2 In some embodiments, Cy 2 Is a cubic alkyl group, where Cy 2 By m R 2 In some embodiments, Cy 2 is adamantyl, where Cy 2 By m R 2 In some embodiments, Cy 2 is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is a 3-7 membered saturated or partially unsaturated monocyclic carbon ring, wherein Cy 2 By m R 2 In some embodiments, Cy 2is a 5-12 membered saturated or partially unsaturated bicyclic carbon ring, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 replace.

[0123] In some embodiments, Cy 2 is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is a 9-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is an 8-9 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is an 8-membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is a 9-membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is a 10-membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 replace.

[0124] In some embodiments, Cy 2 is a 3-7 membered saturated or partially unsaturated monocyclic carbon ring, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is a 4-6 membered saturated or partially unsaturated monocyclic carbon ring, wherein Cy 2By m R 2 In some embodiments, Cy 2 is a 4-5 membered saturated or partially unsaturated monocyclic carbon ring, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is a 5-6 membered saturated or partially unsaturated monocyclic carbon ring, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is a 4-membered saturated or partially unsaturated monocyclic carbon ring, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is a 5-membered saturated or partially unsaturated monocyclic carbon ring, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is a 6-membered saturated or partially unsaturated monocyclic carbon ring, wherein Cy 2 By m R 2 replace.

[0125] In some embodiments, Cy 2 yes where R 2 and m are as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 and m are as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 and m are as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 and m are as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 and m are as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 and m are as defined in the Examples and classes and subclasses herein.

[0126] In some embodiments, Cy 2 yes where R 2As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0127] In some embodiments, Cy 2 is a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is an 8-10 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is an 8-9 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is an 8-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is a 9-membered saturated or partially unsaturated bicyclic heterocycle having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 replace.

[0128] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0129] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0130] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0131] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0132] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0133] In some embodiments, Cy 2 yes wherein R2 is as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0134] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0135] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0136] In some embodiments, Cy 2 yes In some embodiments, Cy2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0137] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0138] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0139] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0140] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0141] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0142] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0143] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0144] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0145] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0146] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0147] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0148] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0149] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0150] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0151] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0152] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0153] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0154] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0155] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0156] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes wherein R2 is as defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the categories and subcategories herein.

[0157] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0158] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the categories and subcategories herein.

[0159] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0160] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0161] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0162] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0163] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0164] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0165] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0166] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0167] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0168] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0169] In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes In some embodiments, Cy 2 yes

[0170] In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes where R 2 As defined in the embodiments and classes and subclasses herein.

[0171] In some embodiments, Cy 2 is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is a 5-6 membered monocyclic heteroaryl ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein Cy 2 By m R 2 In some embodiments, Cy 2 is pyridyl, pyrimidinyl, pyridazinyl, triazinyl or tetrazinyl. In some embodiments, Cy 2 yes Each R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes Each R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes Each R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes Each R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes Each R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes Each R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes Each R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes Each R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes Each R 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, Cy 2 yes Each R 2 As defined in the embodiments and classes and subclasses herein.

[0172] In some embodiments, Cy 2 is a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein Cy 2 By m R 2 In some embodiments, Cy 2 is aziridine, oxirane, azetidinyl, oxetanyl, pyrrolidinyl, piperidinyl, piperazinyl, tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, morpholinyl, tetrahydrothiofuranyl, tetrahydrothiopyranyl, thiomorpholinyl, azepanyl, homomorpholinyl and homothiomorpholinyl. In some embodiments, Cy 2 Is azetidinyl, pyrrolidinyl or piperidinyl. In some embodiments, Cy 2 yes

[0173] In some embodiments, Cy 2 is a group selected from the compounds described in Table 1.

[0174] As generally defined above, Q is L Q , where L Q As defined in the embodiments and classes and subclasses herein.

[0175] In some embodiments, Q is a covalent bond, or C 1-4A divalent saturated or unsaturated linear or branched hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 In some embodiments, Q is a covalent bond. In some embodiments, Q is C 1-4 A divalent saturated or unsaturated linear or branched hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 In some embodiments, Q is C 1-4 A divalent saturated or unsaturated straight or branched hydrocarbon chain.

[0176] In some embodiments, Q is C 1-2 A divalent saturated or unsaturated hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 In some embodiments, Q is C 1-2 A divalent saturated or unsaturated hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, or -O-. In some embodiments, Q is C 1-2 A divalent saturated or unsaturated hydrocarbon chain.

[0177] In some embodiments, Q is -C(O)N(R)-, -C(O)N(R)CH2-, -N(R)-, -CH2C(O)N(R)-, -N(R)C(O)N(R)-, or a covalent bond. In some embodiments, Q is -C(O)N(H)-, -C(O)N(H)CH2-, -N(H)-, -CH2C(O)N(H)-, -N(H)C(O)N(H)-, or a covalent bond. In some embodiments, Q is -C(O)N(H)-, -C(O)N(H)CH2-, or a covalent bond. In some embodiments, Q is -C(O)N(H)- or -C(O)N(H)CH2-. In some embodiments, Q is -C(O)N(H)-. In some embodiments, Q is -C(O)N(H)-. In some embodiments, Q is -C(O)N(H)CH2-. In some embodiments, Q is -N(H)-. In some embodiments, Q is -CH2C(O)N(H)-. In some embodiments, Q is -N(H)C(O)N(H)-. In some embodiments, Q is a covalent bond.

[0178] In some embodiments, Q is selected from the groups depicted in the compounds in Table 1.

[0179] As generally defined above, T is the sum of q R T Substituted divalent C 1-3 In some embodiments, T is replaced by q R T Substituted divalent C 2-3 In some embodiments, T is replaced by q R T Substituted divalent C 1-2 In some embodiments, T is replaced by q R T In some embodiments, T is replaced by q R T In some embodiments, T is replaced by q R T Substituted divalent C3 aliphatic chain.

[0180] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein.

[0181] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein.

[0182] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein.

[0183] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein.

[0184] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein.

[0185] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein.

[0186] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein.

[0187] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein.

[0188] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein.

[0189] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein.

[0190] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TAs defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 and wherein RT is as defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R T As defined in the embodiments and classes and subclasses herein.

[0191] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein.

[0192] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TCAs defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where RTC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TC and r 3 As defined in the embodiments and classes and subclasses herein.

[0193] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein.

[0194] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where RTTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein.

[0195] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein.

[0196] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where RTTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in Indicates the key connected to Q Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein.

[0197] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1As defined in the embodiments and classes and subclasses herein.

[0198] In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is in represents the bond to Q and Indicates connection to Cy 1 The key, and where R TTC and p 1 As defined in the embodiments and classes and subclasses herein. In some embodiments, T is Each R TC As defined in the embodiments and classes and subclasses herein. In some embodiments, T is Each R TC As defined in the embodiments and classes and subclasses herein. In some embodiments, T is Each R TC are independently deuterium, halogen or optionally substituted selected from C 1-6 In some embodiments, T is In some embodiments, T is In some embodiments, T is In some embodiments, T is In some embodiments, T is In some embodiments, T is In some embodiments, T is In some embodiments, T is In some embodiments, T is

[0199] In some embodiments, T is selected from the groups depicted in the compounds in Table 1.

[0200] As generally defined above, each R 1 Independently -L 1 -R 1A ; or two R 1 Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 2 R 11C Replace; or an R T With an R 1 Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 4 R T1C replace.

[0201] In some embodiments, each R 1 Independently -L 1 -R 1A In some embodiments, each R 1 Independently -R 1A .

[0202] In some embodiments, each R 1 Independently R A In some embodiments, each R 1 (i.e., -L 1 -R 1A together) are independently oxo, deuterium, halogen, -CN, -NO2, -OR, -SF5, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -S(O)(NCN)R, -S(NCN)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R )OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2; wherein R is as defined in the embodiments and classes and subclasses herein.

[0203] In some embodiments, R 1 In some embodiments, R 1 In some embodiments, each R 1 In some embodiments, R 1 In some embodiments, R 1 In some embodiments, each R 1 is independently -OR, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, R 1 In some embodiments, each R 1 is independently -SR, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -NR2, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -S(O)2R, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -S(O)2NR2, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, R 1 is -S(O)2F. In some embodiments, each R 1 is independently -S(O)R, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -S(O)NR2, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -S(O)(NR)R, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -S(O)(NCN)R, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -S(NCN)R, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -C(O)R, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -C(O)OR, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -C(O)NR2, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1is independently -C(O)N(R)OR, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -OC(O)R, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -OC(O)NR2, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -N(R)C(O)OR, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -N(R)C(O)R, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -N(R)C(O)NR2, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -N(R)C(NR)NR2, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -N(R)S(O)2NR2, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -N(R)S(O)2R, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -P(O)R2, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -P(O)(R)OR, wherein R is as defined in the Examples and classes and subclasses herein. In some embodiments, each R 1 is independently -B(OR)2, wherein R is as defined in the Examples and classes and subclasses herein.

[0204] In some embodiments, each R 1 Independently 1 R 1C Replaced R B In some embodiments, R 1 (i.e., -L 1 -R 1A Together) is C 1-6aliphatic chain; phenyl; naphthyl; cubanyl; adamantyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is replaced by r 1 R 1C replace.

[0205] In some embodiments, each R 1 (i.e., -L 1 -R 1A together) are independently halogen, -CN, -OR or r 1 Halogen-substituted C 1-6 In some embodiments, each R 1 are independently halogen, -CN, -OR or C substituted by 0-5 halogens 1-6 In some embodiments, each R 1 are independently halogen, -CN, -O-(C 1-6 Aliphatic chain) or C substituted by 0-5 halogens 1-6 In some embodiments, each R 1 is independently halogen or C substituted by 0-5 halogens 1-6 In some embodiments, each R 1 is independently halogen or C substituted by 0-4 halogens 1-6 In some embodiments, each R 1 is independently halogen or C substituted by 0-3 halogens 1-6 In some embodiments, each R 1 is independently halogen or C substituted by 0-3 halogens 1-3 In some embodiments, each R 1 C is independently halogen or substituted by 0-2 halogens 1-3 Aliphatic chain.

[0206] In some embodiments, each R 1 is independently a halogen selected from Br, Cl, and F. In some embodiments, each R 1 is independently a halogen selected from Cl and F. In some embodiments, R 1 In some embodiments, R 1 It's F.

[0207] In some embodiments, at least one R 1 In some embodiments, at least two R 1 In some embodiments, at least three R 1 In some embodiments, one R 1 In some embodiments, the two R 1 In some embodiments, one R 1 is F. In some embodiments, two R 1 is F. In some embodiments, an R 1 is Cl, and an R 1 is F. In some embodiments, two R 1 is Cl, and an R 1 is F. In some embodiments, an R 1 is Cl, and both R 1 It's F.

[0208] In some embodiments, each R 1 is independently C substituted by 0-5 halogens 1-6 In some embodiments, each R 1 is independently C substituted by 0-4 halogens 1-6 In some embodiments, each R 1 is independently C substituted by 0-3 halogens 1-6 In some embodiments, each R 1 is independently C substituted by 0-3 halogens 1-3 In some embodiments, each R 1 is independently C substituted by 0-2 halogens 1-3 Aliphatic chain.

[0209] In some embodiments, at least one R 1 is C optionally substituted by 1-3 halogens 1-3 In some embodiments, at least one R 1 is -OC optionally substituted by 1-3 halogens 1-3 Aliphatic group.

[0210] In some embodiments, each R 1 (i.e., -L 1 -R 1A together) are independently halogen, -OH, -OCH3 or C optionally substituted by 1-3 halogen 1-3 In some embodiments, each R 1is independently fluorine, chlorine, -OCH3 or -CH3. In some embodiments, R 1 In some embodiments, R 1 In some embodiments, R 1 In some embodiments, R 1 In some embodiments, R 1 It is -CHF2.

[0211] In some embodiments, two R 1 Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 2 R 11C Replacement; where p 2 and R 11C As defined in the embodiments and classes and subclasses herein.

[0212] In some embodiments, an R T and an R 1 Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 4 R T1C Replacement; where p 4 and R T1C As defined in the embodiments and classes and subclasses herein.

[0213] In some embodiments, R 1 is a group selected from the compounds described in Table 1.

[0214] As generally defined above, each R2 is independently -L 2 -R 2A ; or two R 2 Together with its intervening atoms, it forms a 3-7 membered saturated, partially unsaturated or aromatic carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 3 R 22C replace.

[0215] In some embodiments, each R 2 Independently -L 2 -R 2A In some embodiments, each R 2 Independently R 2A .

[0216] In some embodiments, R 2 (i.e., -L 2 -R 2A Together) is-N(R)-R 2A , where R and R 2A As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A Together) is -NH-R 2A , where R 2A As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A Together) is -CH(R L )-R 2A , where R and R 2A As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A Together) is -CH2-R 2A , where R 2A As defined in the embodiments and classes 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 classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A Together) is -NHC(O)-R 2A , where R 2A As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is -N(R)C(O)CH(R L )-R 2A , where R and R 2A As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A Together) is -NHC(O)CH2-R 2A , where R 2A As defined in the embodiments and classes and subclasses herein. In some embodiments, R2 (i.e., -L 2 -R 2A Together) is -N(R)C(O)N(R)-R 2A , where R and R 2A As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A Together) is -NHC(O)NH-R 2A , where R 2A is as defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is -N(R)C(O)CH(R L )OR 2A , where R and R 2A As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A Together) is -NHC(O)CH2O-R 2A , where R 2A As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A Together) is -CH(R L )N(R)-R 2A , where R and R 2A As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A Together) is -CH(R L )OR 2A , where R and R 2A As defined in the embodiments and classes and subclasses herein.

[0217] In some embodiments, R 2 Yes-N(R)-R 2A 、-N(R)C(O)-R 2A 、-CH(R L )N(R)-R 2A 、-N(R)C(O)CH(R L )-R 2A 、-CH(R L )OR 2A 、-CH(R L)-R 2A or -R 2A In some embodiments, R 2 Yes-N(R)-R 2A 、-N(R)C(O)-R 2A 、-CH(R L )N(R)-R 2A or -R 2A In some embodiments, R 2 Yes-N(R)-R 2A 、-N(R)C(O)-R 2A or -R 2A In some embodiments, R 2 Yes-N(R)C(O)-R 2A or -R 2A .

[0218] In some embodiments, R 2 Yes-N(H)-R 2A 、-N(H)C(O)-R 2A 、-CH2N(H)-R 2A 、-N(H)C(O)CH2-R 2A 、-CH2O-R 2A 、-CH2-R 2A or -R 2A In some embodiments, R 2 Yes-N(H)-R 2A 、-N(H)C(O)-R 2A 、-CH2N(H)-R 2A or -R 2A In some embodiments, R 2 Yes-N(H)-R 2A 、-N(H)C(O)-R 2A or -R 2A In some embodiments, R 2 is -N(H)C(O)-R 2A or -R 2A .

[0219] In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein.

[0220] In some embodiments, R 2 (i.e., -L2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein.

[0221] In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2As defined in the embodiments and classes and subclasses herein.

[0222] In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein.

[0223] In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2Atogether) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein.

[0224] In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein.

[0225] In some embodiments, R 2 (i.e., -L 2 -R 2A together) is

[0226] In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein.

[0227] In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein.

[0228] In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein.

[0229] In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein.

[0230] In some embodiments, R 2(i.e., -L 2 -R 2A together) is

[0231] where R 2C and r 2 As defined in the embodiments and classes and subclasses herein.

[0232] In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2As defined in the embodiments and classes and subclasses herein.

[0233] In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2A 、R 2C and r 2 As defined in the embodiments and classes and subclasses herein.

[0234] In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein. In some embodiments, R 2 (i.e., -L 2 -R 2A together) is where R 2C and r 2 As defined in the embodiments and classes and subclasses herein.

[0235] In some embodiments, each R2 (i.e., -L 2 -R 2A together) are independently halogen, -OH, -OCH3 or C optionally substituted by 1-3 halogen 1-3 In some embodiments, each R 2 is independently fluorine, chlorine, -OCH3 or -CH3. In some embodiments, R 2 In some embodiments, R 2 In some embodiments, R 2 In some embodiments, R 2 In some embodiments, R 2 It is -CHF2.

[0236] In some embodiments, two R 2 Together with its intervening atoms, it forms a 3-7 membered saturated, partially unsaturated or aromatic carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 3 R 22C In some embodiments, two R 2 Together with its intervening atoms, it forms a 3-7 membered saturated, partially unsaturated or aromatic carbocyclic ring; wherein the ring is 3 R 22C In some embodiments, two R 2 Together with its intervening atoms, it forms a 6-membered aromatic carbocyclic ring; wherein the ring is p 3 R 22C replace.

[0237] In some embodiments, R 2 is a group selected from the compounds described in Table 1.

[0238] As generally defined above, each R T Independently -L T -R TA ; or two R T Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 1 R TTC Replace; or one RT and one R 1 Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 4 RT1C Replace; or an R T and an R L Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 5 R TLC replace.

[0239] In some embodiments, each R T Independently -L T -R TA In some embodiments, each R T Independently -R TA In some embodiments, each R T Independently R A In some embodiments, each R T Independently 3 R TC Replaced R B .

[0240] In some embodiments, R T (i.e., -LT-R TA Together) is C 1-6 aliphatic chain; phenyl; naphthyl; cubanyl; adamantyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is replaced by r 3 R TC replace.

[0241] In some embodiments, R T It is C 1-6 aliphatic chain; adamantyl; a 3-7 membered saturated or partially unsaturated monocyclic carbocycle; a 5-12 membered saturated or partially unsaturated bicyclic carbocycle; a 3-7 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC replace.

[0242] In some embodiments, R Tis a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; each of which is r 3 R TC In some embodiments, RT is a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each of which is replaced by r 3 R TC replace.

[0243] In some embodiments, R T is a 3-7 membered saturated monocyclic carbocycle; a 5-12 membered saturated bicyclic carbocycle; a 3-7 membered saturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC In some embodiments, R T is a 3-7 membered saturated monocyclic carbocyclic ring; or a 5-12 membered saturated bicyclic carbocyclic ring; each of which is r 3 R TC In some embodiments, R T is a 3-7 membered saturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC replace.

[0244] In some embodiments, R T (i.e., -L T -R TA Together) is r 3 R TC Substituted C 1-6 In some embodiments, R T (i.e., -L T -R TA Together) is r 3 R TC In some embodiments, R T (i.e., -L T -R TA Together) is r 3 R TC In some embodiments, R T (i.e., -L T -R TA Together) is r 3 R TCIn some embodiments, R T (i.e., -L T -R TA Together) is r 3 R TC In some embodiments, R T (i.e., -L T -R TA together) is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the ring is r 3 R TC In some embodiments, R T (i.e., -L T -R TA together) is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the ring is r 3 R TC In some embodiments, R T (i.e., -L T -R TA together) is a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, wherein the ring is r 3 R TC In some embodiments, RT (ie, -L T -R TA together) is a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring, wherein the ring is surrounded by r 3 R TC In some embodiments, R T (i.e., -L T -R TA together) is a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the ring is r 3 R TC In some embodiments, R T (i.e., -L T -R TA together) is a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the ring is r 3 R TC replace.

[0245] In some embodiments, RT is

[0246] In some embodiments, R T yes In some embodiments, R T yes In some embodiments, R T yes In some embodiments, R T yes In some embodiments, R T yes In some embodiments, R T yes In some embodiments, R T yes In some embodiments, R T yes In some embodiments, R T yes In some embodiments, R T is CF3. In some embodiments, R T is r 3 R TC Substituted C 1-6 In some embodiments, R T is r 3 R TC Substituted C 3-8 Cycloalkyl.

[0247] In some embodiments, two R r Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 1 R TTC replace.

[0248] In some embodiments, an R T and an R 1 Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 4 R T1C replace.

[0249] In some embodiments, an R T and an R L Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is p 5 R TLC replace.

[0250] In some embodiments, R T is a group selected from the compounds described in Table 1.

[0251] As generally defined above, L 1 Is a covalent bond or C 1-4 A divalent saturated or unsaturated linear or branched hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 In some embodiments, L 1 is a covalent bond. In some embodiments, L 1 It is C 1-4 A divalent saturated or unsaturated linear or branched hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 In some embodiments, L 1 It is C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chain.

[0252] In some embodiments, L 1 It is C 1-2 A divalent saturated or unsaturated hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 In some embodiments, L 1 It is C 1-2 A divalent saturated or unsaturated hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(RL )-、-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 It is C 1-2 A divalent saturated or unsaturated hydrocarbon chain.

[0253] In some embodiments, L 1 is a group selected from the compounds described in Table 1.

[0254] As generally defined above, L 2 Is a covalent bond or C 1-4 A divalent saturated or unsaturated linear or branched hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 In some embodiments, L 2 is a covalent bond. In some embodiments, L 2 It is C 1-4 A divalent saturated or unsaturated linear or branched hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 In some embodiments, L 2 It is C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chain.

[0255] In some embodiments, L 2 It is C 1-2 A divalent saturated or unsaturated hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6Cycloalkylene, C 3-6 In some embodiments, L 2 It is C 1-2 A divalent saturated or unsaturated hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, or -O-. In some embodiments, L 2 It is C 1-2 A divalent saturated or unsaturated hydrocarbon chain.

[0256] In some embodiments, L 2 Is -N(R)-, -N(R)C(O)-, -CH(R L )N(R)-、-N(R)C(O)CH(R L )-、-CH(R L )O-、-CH(R L )- or covalent bond. In some embodiments, R 2 Is -N(R)-, -N(R)C(O)-, -CH(R L )N(R)- or covalent bond. In some embodiments, R 2 is -N(R)-, -N(R)C(O)- or a covalent bond. In some embodiments, R 2 It is -N(R)C(O)- or a covalent bond.

[0257] In some embodiments, R 2 is -N(H)-, -N(H)C(O)-, -CH2N(H)-, -N(H)C(O)CH2-, -CH2O-, -CH2-, or a covalent bond. In some embodiments, R 2 is -N(H)-, -N(H)C(O)-, -CH2N(H)- or a covalent bond. In some embodiments, R 2 is -N(H)-, -N(H)C(O)- or a covalent bond. In some embodiments, R 2 It is -N(H)C(O)- or a covalent bond.

[0258] In some embodiments, L 2 is -N(R)C(O)- or -N(R)C(O)N(R)-. In some embodiments, L2 is -N(H)C(O)- or -N(H)C(O)N(H)-. In some embodiments, L 2 is -N(R)C(O)-. In some embodiments, L 2 is -N(H)C(O)-. In some embodiments, L 2 is -N(R)C(O)N(R)-. In some embodiments, L 2 is -N(H)C(O)N(H)-. In some embodiments, L 2 is -N(R)-. In some embodiments, L 2 is -N(H)-. In some embodiments, L 2 is a covalent bond. In some embodiments, L 2 is -CH(R L )N(R)-. In some embodiments, L 2 is -N(R)C(O)CH(R L )-. In some embodiments, L 2 is -CH(R L )O-. In some embodiments, L 2 is -CH(R L )-.

[0259] In some embodiments, L 2 is a group selected from the compounds described in Table 1.

[0260] As generally defined above, L Q Is a covalent bond or C 1-4 A divalent saturated or unsaturated linear or branched hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 In some embodiments, L Q is a covalent bond. In some embodiments, L Q It is C 1-4 A divalent saturated or unsaturated linear or branched hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6In some embodiments, L Q It is C 1-4 Divalent saturated or unsaturated, straight or branched hydrocarbon chain.

[0261] In some embodiments, L Q It is C 1-2 A divalent saturated or unsaturated hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 In some embodiments, LQ is C 1-2 A divalent saturated or unsaturated hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, or -O-. In some embodiments, L Q It is C 1-2 A divalent saturated or unsaturated hydrocarbon chain.

[0262] In some embodiments, L Q is -C(O)N(R)-, -C(O)N(R)CH2-, -N(R)-, -CH2C(O)N(R)-, -N(R)C(O)N(R)-, or a covalent bond. In some embodiments, L Q is -C(O)N(H)-, -C(O)N(H)CH2-, -N(H)-, -CH2C(O)N(H)-, -N(H)C(O)N(H)-, or a covalent bond. In some embodiments, L Q is -C(O)N(H)-, -C(O)N(H)CH2- or a covalent bond. In some embodiments, L Q is -C(O)N(H)- or -C(O)N(H)CH2-. In some embodiments, L Q is -C(O)N(H)-. In some embodiments, LQ is -C(O)N(H)CH2-. In some embodiments, L Q is -N(H)-. In some embodiments, L Q is -CH2C(O)N(H)-. In some embodiments, L Q is -N(H)C(O)N(H)-. In some embodiments, L Q It is a covalent bond.

[0263] In some embodiments, L Q is a group selected from the compounds described in Table 1.

[0264] As generally defined above, L T Is a covalent bond or C 1-4 A divalent saturated or unsaturated linear or branched hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 In some embodiments, L T is a covalent bond. In some embodiments, L T It is C 1-4 A divalent saturated or unsaturated linear or branched hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 In some embodiments, L X It is C 1-4 A divalent saturated or unsaturated straight or branched hydrocarbon chain.

[0265] In some embodiments, L T It is C 1-2 A divalent saturated or unsaturated hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L)2-、C 3-6 Cycloalkylene, C 3-6 In some embodiments, L T It is C 1-2 A divalent saturated or unsaturated hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-, -N(R)-, -N(R)C(O)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, or -O-. In some embodiments, L T It is C 1-2 A divalent saturated or unsaturated hydrocarbon chain.

[0266] In some embodiments, L T is a group selected from the compounds described in Table 1.

[0267] As generally defined above, each R 1A Independently 1 R 1C Replaced R A or R B In some embodiments, each R 1A Independently R A In some embodiments, each R 1A Independently 1 R 1C Replaced R B .

[0268] In some embodiments, R 1A is phenyl; naphthyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R 1A R 1 R 1C replace.

[0269] In some embodiments, R 1Ais r 1 R 1C In some embodiments, R 1A is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R 1A R 1 R 1C In some embodiments, R 1A is phenyl or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R 1A R 1 R 1C replace.

[0270] In some embodiments, R 1A is phenyl; naphthyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; wherein R 1A R 1 R 1C replace.

[0271] In some embodiments, R 1A is r 1 wherein the phenyl group is substituted with one or more of the following groups: oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR), and optionally substituted C(O) 1-6 In some embodiments, R 1A is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R 1A R 1wherein the substituted radicals are selected from the group consisting of oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR), and optionally substituted C(O) 1-6 In some embodiments, R 1A is phenyl or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R 1A R 1 wherein the substituted radicals are selected from the group consisting of oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR), and optionally substituted C(O) 1-6 Aliphatic group.

[0272] In some embodiments, R 1A Is 1-3 R 1C In some embodiments, R 1A It is 2 R 1C In some embodiments, R 1A Is 1 R 1C Substituted phenyl.

[0273] In some embodiments, R 1A is phenyl substituted by 1-3 groups independently selected from the group consisting of halogen, -CN, -O-(optionally substituted C 1-6 aliphatic) and optionally substituted C 1-6 In some embodiments, R 1A is phenyl substituted by 1-3 groups independently selected from the group consisting of halogen and C optionally substituted by 1-3 halogens1-3 In some embodiments, R 1A is phenyl substituted with 1 to 3 groups independently selected from fluoro, chloro, -CH3, -CHF2 and -CF3.

[0274] In some embodiments, R 1A is phenyl substituted by 2 groups independently selected from the group consisting of halogen, -CN, -O-(optionally substituted C 1-6 aliphatic) and optionally substituted C 1-6 In some embodiments, R 1A is phenyl substituted by 2 groups independently selected from the group consisting of halogen and C optionally substituted by 1-3 halogens 1-3 In some embodiments, R 1A is phenyl substituted with two groups independently selected from the group consisting of fluoro, chloro, -CH3, -CHF2 and -CF3.

[0275] In some embodiments, R 1A is phenyl substituted by a group selected from halogen, -CN, -O-(optionally substituted C 1-6 aliphatic) and optionally substituted C 1-6 In some embodiments, R 1A is phenyl substituted by one halogen or C optionally substituted by 1 to 3 halogens 1-3 In some embodiments, R 1A It is a phenyl group substituted by one fluorine, chlorine, -CH3, -CHF2 or -CF3.

[0276] In some embodiments, each R 1A and -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, -B(OR), or deuterium.

[0277] In some embodiments, each R 1Aand -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR).

[0278] In some embodiments, R 1A In some embodiments, each R 1A In some embodiments, R 1A In some embodiments, R 1A In some embodiments, each R 1A In some embodiments, each R 1A In some embodiments, each R 1A In some embodiments, each R 1A is independently -S(O)2R. In some embodiments, each R 1A In some embodiments, R 1A is -S(O)2F. In some embodiments, each R 1A is independently -S(O)R. In some embodiments, each R 1A is independently -S(O)NR2. In some embodiments, each R 1A is independently -S(O)(NR)R. In some embodiments, each R 1A is independently -C(O)R. In some embodiments, each R 1A is independently -C(O)OR. In some embodiments, each R 1A is independently -C(O)NR2. In some embodiments, each R 1A is independently -C(O)N(R)OR. In some embodiments, each R 1A is independently -OC(O)R. In some embodiments, each R 1A In some embodiments, each R 1A is independently -N(R)C(O)OR. In some embodiments, each R 1Ais independently -N(R)C(O)R. In some embodiments, each R 1A is independently -N(R)C(O)NR2. In some embodiments, each R 1A is independently -N(R)C(NR)NR2. In some embodiments, each R 1A is independently -N(R)S(O)2NR2. In some embodiments, each R 1A is independently -N(R)S(O)2R. In some embodiments, each R 1A is independently -P(O)R2. In some embodiments, each R 1A is independently -P(O)(R)OR. In some embodiments, each R 1A is independently -B(OR)2. In some embodiments, R 1A It's deuterium.

[0279] In some embodiments, R 1A Is halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC (O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0280] In some embodiments, R 1A is halogen, -CN or -NO2. In some embodiments, R 1A Is -OR, -SR or -NR2. In some embodiments, R 1A is -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2 or -S(O)(NR)R. In some embodiments, R 1A is -C(O)R, -C(O)OR, -C(O)NR2 or -C(O)N(R)OR. In some embodiments, R 1A Is -OC(O)R or -OC(O)NR2. In some embodiments, R 1A In some embodiments, R 1AIt is -P(O)R2 or -P(O)(R)OR.

[0281] In some embodiments, R 1A is -OR, -OC(O)R or -OC(O)NR2. In some embodiments, R 1A 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.

[0282] In some embodiments, R 1A is -S(O)2R, -S(O)2NR2 or -S(O)2F. In some embodiments, R 1A is -S(O)R, -S(O)NR2 or -S(O)(NR)R. In some embodiments, R 1A Is -SR, -S(O)2R or -S(O)R. In some embodiments, R 1A is -S(O)2NR2, -S(O)NR2 or -S(O)(NR)R. In some embodiments, R 1A Is -S(O)2NR2 or -S(O)NR2. In some embodiments, R 1A It is -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0283] In some embodiments, R 1A is -N(R)C(O)OR, -N(R)C(O)R or -N(R)C(O)NR2. In some embodiments, R 1A is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R 1A is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R 1A is -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R 1A It is -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0284] In some embodiments, R 1A is -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)C(O)NR2. In some embodiments, R 1Ais -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.

[0285] In some embodiments, R 1A It is C 1-6 aliphatic chain; phenyl; naphthyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is replaced by r 1 R 1C replace.

[0286] In some embodiments, R 1A is r 1 R 1C Substituted C 1-6 In some embodiments, R 1A is r 1 R 1C In some embodiments, R 1A is r 1 R 1C In some embodiments, R 1A is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r 1 R 1C In some embodiments, R 1A is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r 1 R 1C In some embodiments, R 1A is r 1 R 1C substituted 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring. 1A is r 1 R 1C substituted 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring. 1A is a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r1 R 1C In some embodiments, R 1A is a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r 1 R 1C replace.

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

[0288] In some embodiments, R 1A is phenyl; naphthyl; 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; or 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; each of which is r 1 R 1C In some embodiments, R 1A is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is replaced by 1 R 1C replace.

[0289] In some embodiments, R 1A is phenyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 1 R 1C In some embodiments, R 1Ais naphthyl; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 1 R 1C replace.

[0290] In some embodiments, R 1A is phenyl or naphthyl; each of which is r 1 R 1C In some embodiments, R 1A is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 1 R 1C In some embodiments, R 1A is a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; each of which is replaced by r1 R 1C In some embodiments, R 1A is a 3-7 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 1 R 1C replace.

[0291] In some embodiments, R 1A is phenyl or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is replaced by r 1 R 1C In some embodiments, R 1A is a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 1 R 1C In some embodiments, R 1A is naphthyl or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 1 R 1C In some embodiments, R 1A is a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring, or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 1 R1C replace.

[0292] In some embodiments, R 1A is phenyl or a 3-7 membered saturated or partially unsaturated monocyclic carbon ring; each of which is r 1 R 1C In some embodiments, R 1A is naphthyl or a 5-12 membered saturated or partially unsaturated bicyclic carbon ring; each of which is r 1 R 1C In some embodiments, R 1A is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 1 R 1C In some embodiments, R 1A is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 1 R 1C replace.

[0293] In some embodiments, R 1A It is C 1-6 aliphatic chain; a 3-7 membered saturated or partially unsaturated monocyclic carbocycle; a 5-12 membered saturated or partially unsaturated bicyclic carbocycle; a 3-7 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 1 R 1C In some embodiments, R 1A It is C 1-6 Aliphatic chain; phenyl; naphthyl; 3-7 membered saturated or partially unsaturated monocyclic carbon ring; or 5-12 membered saturated or partially unsaturated bicyclic carbon ring; each of which is r 1 R 1C In some embodiments, R 1A It is C 1-6 aliphatic chain; phenyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 1 R 1C replace.

[0294] In some embodiments, R 1A It is C 1-6 aliphatic chain, a 3-7 membered saturated or partially unsaturated monocyclic carbon ring, or a 5-12 membered saturated or partially unsaturated bicyclic carbon ring; each of which is r 1 R 1C In some embodiments, R 1A It is C 1-6 an aliphatic chain, a 3-7 membered saturated or partially unsaturated monocyclic carbon ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 1 R 1C In some embodiments, R 1A It is C 1-6 Aliphatic chain, phenyl or 3-7 membered saturated or partially unsaturated monocyclic carbon ring; each of which is r 1 R 1C replace.

[0295] In some embodiments, each R 1A are independently halogen, -CN, -OR or r 1 Halogen-substituted C 1-6 In some embodiments, each R 1A are independently halogen, -CN, -OR or C substituted by 0-5 halogens 1-6 In some embodiments, each R 1A are independently halogen, -CN, -O-(C 1-6 Aliphatic chain) or C substituted by 0-5 halogens 1-6 In some embodiments, each R 1A is independently halogen or C substituted by 0-5 halogens 1-6 In some embodiments, each R 1A is independently halogen or C substituted by 0-4 halogens 1-6 In some embodiments, each R 1A is independently halogen or C substituted by 0-3 halogens 1-6 In some embodiments, each R 1A is independently halogen or C substituted by 0-3 halogens 1-3 In some embodiments, each R 1A C is independently halogen or substituted by 0-2 halogens 1-3 Aliphatic chain.

[0296] In some embodiments, each R 1A is independently a halogen selected from Br, Cl, and F. In some embodiments, each R1A is independently a halogen selected from Cl and F. In some embodiments, R 1A In some embodiments, R 1A It's F.

[0297] In some embodiments, at least one R 1A In some embodiments, at least two R 1A In some embodiments, at least three R 1A In some embodiments, one R 1A In some embodiments, the two R 1A is C1. In some embodiments, an R 1A is F. In some embodiments, two R 1A is F. In some embodiments, an R 1A is Cl, and an R 1A is F. In some embodiments, two R 1A is Cl, and an R 1A is F. In some embodiments, an R 1A is Cl, and both R 1A It's F.

[0298] In some embodiments, R 1A is C substituted with 0-5 halogens 1-6 In some embodiments, R 1A is C substituted by 0-4 halogens 1-6 In some embodiments, R 1A is C substituted by 0-3 halogens 1-6 In some embodiments, R 1A is C substituted by 0-3 halogens 1-3 In some embodiments, R 1A is C substituted by 0-2 halogens 1-3 Aliphatic chain.

[0299] In some embodiments, at least one R 1A is C optionally substituted by 1-3 halogens 1-3 In some embodiments, at least one R 1A is -OC optionally substituted by 1-3 halogens 1-3 Aliphatic group.

[0300] In some embodiments, each R 1A is independently halogen, -OH, -OCH3 or C optionally substituted by 1-3 halogens 1-3 In some embodiments, each R1A is independently fluorine, chlorine, -OCH3 or -CH3. In some embodiments, R 1A In some embodiments, R 1A In some embodiments, R 1A In some embodiments, R 1A In some embodiments, R 1A It is -CHF2.

[0301] In some embodiments, R 1A is a group selected from the compounds described in Table 1.

[0302] As generally defined above, each R 2A Independently 2 R 2C Replaced R A or R B In some embodiments, each R 2A It is R A In some embodiments, each R 2A is r 2 R 2C Replaced R B .

[0303] In some embodiments, R 2A is phenyl; naphthyl; cubanyl; adamantyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R 2A is r 2 R 2C replace.

[0304] In some embodiments, R 2A is phenyl; naphthyl; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R 2A R 2 R 2C In some embodiments, R 2Ais phenyl; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R 2A R 2 R 2C In some embodiments, R 2A is phenyl or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R 2A R 2 R 2C replace.

[0305] In some embodiments, R 2A is phenyl; naphthyl; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R 2A R 2 wherein the substituted radicals are selected from the group consisting of oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR), and optionally substituted C(O) 1-6 In some embodiments, R 2A is phenyl; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R 2A R 2wherein the substituted radicals are selected from the group consisting of oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR), and optionally substituted C(O) 1-6 In some embodiments, R 2A is phenyl or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R 2A R 2 wherein the substituted radicals are selected from the group consisting of oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR), and optionally substituted C(O) 1-6 Aliphatic group.

[0306] In some embodiments, R 2A is r 2 R 2C In some embodiments, R 2A is r 2wherein the phenyl group is substituted with one or more of the following groups: oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR), and optionally substituted C(O) 1-6 Aliphatic group.

[0307] In some embodiments, R 2A is phenyl substituted by 1-3 groups independently selected from the group consisting of halogen, -CN, -O-(optionally substituted C 1-6 aliphatic) and optionally substituted C 1-6 In some embodiments, R 2A is phenyl substituted by 1-3 groups independently selected from the group consisting of halogen and C optionally substituted by 1-3 halogens 1-3 In some embodiments, R 2A is phenyl substituted with 1 to 3 groups independently selected from fluoro, chloro, -CH3, -CHF2 and -CF3.

[0308] In some embodiments, R 2A is phenyl substituted by 2 groups independently selected from the group consisting of halogen, -CN, -O-(optionally substituted C 1-6 aliphatic) and optionally substituted C 1-6 In some embodiments, R 2A is phenyl substituted by 2 groups independently selected from the group consisting of halogen and C optionally substituted by 1-3 halogens 1-3 In some embodiments, R 2A It is phenyl substituted with two groups independently selected from the group consisting of fluorine, chlorine, -CH3, -CHF2 and -CF3.

[0309] In some embodiments, R 2A is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R 2A R 2 R 2C In some embodiments, R 2Ais an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R 2A R 2 wherein the substituted radicals are selected from the group consisting of oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, -B(OR), and optionally substituted C(O) 1-6 Aliphatic group.

[0310] In some embodiments, R 2A is an 8-10 membered bicyclic heteroaryl ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R 2A R 2 R 2C In some embodiments, R 2A is an 8-10 membered bicyclic heteroaryl ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R 2A R 2 wherein the substituted alkyl radicals are selected from the group consisting of oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2, and optionally substituted C(O) 1-6 Aliphatic group.

[0311] In some embodiments, R 2A is an 8-10 membered bicyclic heteroaryl ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R 2A is substituted by 0-2 groups independently selected from the group consisting of halogen, -CN, -O-(optionally substituted C 1-6 aliphatic) and optionally substituted C1-6 In some embodiments, R 2A is an 8-10 membered bicyclic heteroaryl ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R 2A is substituted by 0-2 groups independently selected from the group consisting of halogen and C optionally substituted by 1-3 halogens 1-3 In some embodiments, R 2A is an 8-10 membered bicyclic heteroaryl ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R 2A Substituted with 0-2 groups independently selected from fluoro, chloro, -CH3, -CHF2 and -CF3.

[0312] In some embodiments, R 2A Is oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -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.

[0313] In some embodiments, R 2A Is oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, - OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0314] In some embodiments, R 2A In some embodiments, R 2A In some embodiments, R 2A In some embodiments, R 2A In some embodiments, R 2A In some embodiments, R2A In some embodiments, R 2A In some embodiments, R 2A is -S(O)2R. In some embodiments, R 2A In some embodiments, R 2A is -S(O)2F. In some embodiments, R 2A is -S(O)R. In some embodiments, R 2A is -S(O)NR2. In some embodiments, R 2A is -S(O)(NR)R. In some embodiments, R 2A is -C(O)R. In some embodiments, R 2A In some embodiments, R 2A In some embodiments, R 2A is -C(O)N(R)OR. In some embodiments, R 2A is -OC(O)R. In some embodiments, R 2A In some embodiments, R 2A is -N(R)C(O)OR. In some embodiments, R 2A is -N(R)C(O)R. In some embodiments, R 2A is -N(R)C(O)NR2. In some embodiments, R 2A is -N(R)C(NR)NR2. In some embodiments, R 2A is -N(R)S(O)2NR2. In some embodiments, R 2A is -N(R)S(O)2R. In some embodiments, R 2A is -P(O)R2. In some embodiments, R 2A is -P(O)(R)OR. In some embodiments, R 2A is -B(OR)2. In some embodiments, R 2A It's deuterium.

[0315] In some embodiments, R 2AIs 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.

[0316] In some embodiments, R 2A is halogen, -CN or -NO2. In some embodiments, R 2A Is -OR, -SR or -NR2. In some embodiments, R 2A In some embodiments, R 2A is -C(O)R, -C(O)OR, -C(O)NR2 or -C(O)N(R)OR. In some embodiments, R 2A Is -OC(O)R or -OC(O)NR2. In some embodiments, R 2A In some embodiments, R 2A It is -P(O)R2 or -P(O)(R)OR.

[0317] In some embodiments, R 2A is -OR, -OC(O)R or -OC(O)NR2. In some embodiments, R 2A 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.

[0318] In some embodiments, R 2A is -S(O)2R, -S(O)2NR2 or -S(O)2F. In some embodiments, R 2Ais -S(O)R, -S(O)NR2 or -S(O)(NR)R. In some embodiments, R 2A Is -SR, -S(O)2R or -S(O)R. In some embodiments, R 2A is -S(O)2NR2, -S(O)NR2 or -S(O)(NR)R. In some embodiments, R 2A Is -S(O)2NR2 or -S(O)NR2. In some embodiments, R 2A It is -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0319] In some embodiments, R 2A is -N(R)C(O)OR, -N(R)C(O)R or -N(R)C(O)NR2. In some embodiments, R 2A is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R 2A is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R 2A is -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R 2A It is -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0320] In some embodiments, R 2A is -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)C(O)NR2. In some embodiments, R 2A is -NR2, -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R 2A It is -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0321] In some embodiments, R 2A It is C 1-6 aliphatic chain; phenyl; naphthyl; cubanyl; adamantyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is replaced by r 2 R2C replace.

[0322] In some embodiments, R 2A is r 2 R 2C Substituted C 1-6 In some embodiments, R 2A is r 2 R 2C In some embodiments, R 2A is r 2 R 2C In some embodiments, R 2A is r 2 R 2C In some embodiments, R 2A is r 2 R 2C In some embodiments, R 2A is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r 2 R 2C In some embodiments, R 2A is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r 2 R 2C In some embodiments, R 2A is r 2 R 2C substituted 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring. 2A is r 2 R 2C In some embodiments, R 2A is a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r 2 R 2C In some embodiments, R 2A is a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r 2 R 2C replace.

[0323] In some embodiments, R 2Ais phenyl; naphthyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 2 R 2C In some embodiments, R 2A is a cubic alkyl group; an adamantyl group; a 3-7 membered saturated or partially unsaturated monocyclic carbocycle; a 5-12 membered saturated or partially unsaturated bicyclic carbocycle; a 3-7 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 2 R 2C replace.

[0324] In some embodiments, R 2A is phenyl; naphthyl; cubic alkyl; adamantyl; 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; or 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; each of which is r 2 R 2C In some embodiments, R 2A is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is replaced by 2 R 2C replace.

[0325] In some embodiments, R 2A is phenyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 2 R 2C In some embodiments, R 2A is naphthyl; cubic alkyl; adamantyl; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 2 R 2C replace.

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

[0327] In some embodiments, R 2A is phenyl or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is replaced by r 2 R 2C In some embodiments, R 2A is a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 2 R 2C In some embodiments, R 2A is naphthyl or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 2 R 2C In some embodiments, R 2A is a cubic alkyl group; adamantyl group; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 2 R 2C replace.

[0328] In some embodiments, R 2A is phenyl or a 3-7 membered saturated or partially unsaturated monocyclic carbon ring; each of which is r 2 R 2C In some embodiments, R2A is naphthyl; cubic alkyl; adamantyl; or a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; each of which is r 2 R 2C In some embodiments, R 2A is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 2 R 2C In some embodiments, R 2A is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 2 R 2C replace.

[0329] In some embodiments, R 2A It is C 1-6 aliphatic chain; cubic alkyl; adamantyl; 3-7 membered saturated or partially unsaturated monocyclic carbocycle; 5-12 membered saturated or partially unsaturated bicyclic carbocycle; 3-7 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 2 R 2C In some embodiments, R 2A It is C 1-6 Aliphatic chain; phenyl; naphthyl; cubic alkyl; adamantyl; 3-7 membered saturated or partially unsaturated monocyclic carbon ring; or 5-12 membered saturated or partially unsaturated bicyclic carbon ring; each of which is r 2 R 2C In some embodiments, R 2A It is C 1-6 aliphatic chain; phenyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 2 R 2C replace.

[0330] In some embodiments, R 2A It is C 1-6 aliphatic chain, cubic alkyl, adamantyl, 3-7 membered saturated or partially unsaturated monocyclic carbon ring, or 5-12 membered saturated or partially unsaturated bicyclic carbon ring; each of which is r 2R 2C In some embodiments, R 2A It is C 1-6 an aliphatic chain, a 3-7 membered saturated or partially unsaturated monocyclic carbon ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 2 R 2C In some embodiments, R 2A It is C 1-6 Aliphatic chain, phenyl or 3-7 membered saturated or partially unsaturated monocyclic carbon ring; each of which is r 2 R 2C replace.

[0331] In some embodiments, R 2A is a group selected from the compounds described in Table 1.

[0332] As generally defined above, each R TA Independently 3 R TC Replaced R A or R B In some embodiments, each R T Independently R A In some embodiments, each R T Independently 3 R TC Replaced R B .

[0333] In some embodiments, R TA Is oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -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.

[0334] In some embodiments, R TAIs 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.

[0335] In some embodiments, R TA In some embodiments, R TA In some embodiments, R TA In some embodiments, R TA In some embodiments, R TA In some embodiments, R TA In some embodiments, R TA In some embodiments, R TA is -S(O)2R. In some embodiments, R TA In some embodiments, R TA is -S(O)2F. In some embodiments, R TA is -S(O)R. In some embodiments, R TA is -S(O)NR2. In some embodiments, R TA is -S(O)(NR)R. In some embodiments, R TA is -C(O)R. In some embodiments, R SA In some embodiments, R TA In some embodiments, R TA is -C(O)N(R)OR. In some embodiments, R TA is -OC(O)R. In some embodiments, R TA In some embodiments, R TA is -N(R)C(O)OR. In some embodiments, R TA is -N(R)C(O)R. In some embodiments, R TA is -N(R)C(O)NR2. In some embodiments, R TA is -N(R)C(NR)NR2. In some embodiments, R TAis -N(R)S(O)2NR2. In some embodiments, R TA is -N(R)S(O)2R. In some embodiments, R TA is -P(O)R2. In some embodiments, R TA is -P(O)(R)OR. In some embodiments, R TA is -B(OR)2. In some embodiments, R TA It's deuterium.

[0336] In some embodiments, R TA Is halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC (O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0337] In some embodiments, R TA is halogen, -CN or -NO2. In some embodiments, R TA Is -OR, -SR or -NR2. In some embodiments, R TA In some embodiments, R TA is -C(O)R, -C(O)OR, -C(O)NR2 or -C(O)N(R)OR. In some embodiments, R SA Is -OC(O)R or -OC(O)NR2. In some embodiments, R SA In some embodiments, R TA It is -P(O)R2 or -P(O)(R)OR.

[0338] In some embodiments, R TA is -OR, -OC(O)R or -OC(O)NR2. In some embodiments, R TAIn some embodiments, R SA 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.

[0339] In some embodiments, R TA is -S(O)2R, -S(O)2NR2 or -S(O)2F. In some embodiments, R TA is -S(O)R, -S(O)NR2 or -S(O)(NR)R. In some embodiments, R TA Is -SR, -S(O)2R or -S(O)R. In some embodiments, R TA is -S(O)2NR2, -S(O)NR2 or -S(O)(NR)R. In some embodiments, R TA Is -S(O)2NR2 or -S(O)NR2. In some embodiments, R TA It is -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

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

[0341] In some embodiments, R TA is -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)C(O)NR2. In some embodiments, R TA is -NR2, -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R TA It is -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0342] In some embodiments, R TA It is C 1-6 aliphatic chain; phenyl; naphthyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is replaced by r 3 R TC replace.

[0343] In some embodiments, R TA is r 3 R TC Substituted C 1-6 In some embodiments, R TA is r 3 R TC In some embodiments, R TA is r 3 R TC In some embodiments, R TA is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r 3 R TC In some embodiments, R TA is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r 3 R TC In some embodiments, R TA is r 3 R TC substituted 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring. TA is r 3 R TC In some embodiments, R TA is a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r 3 R TC In some embodiments, R TA is a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r 3 RTC replace.

[0344] In some embodiments, R TA is phenyl; naphthyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is replaced by r 3 R TC replace.

[0345] In some embodiments, R TA is phenyl; naphthyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC In some embodiments, R TA is a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC replace.

[0346] In some embodiments, R TA is phenyl; naphthyl; 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; or 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; each of which is r 3 R TC In some embodiments, R TA is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is replaced by 3 R TC replace.

[0347] In some embodiments, R TAis phenyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC In some embodiments, R TA is naphthyl; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC replace.

[0348] In some embodiments, R TA is phenyl or naphthyl; each of which is r 3 R TC In some embodiments, R TA is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC In some embodiments, R TA is a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring or a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; each of which is r 3 R TC In some embodiments, R TA is a 3-7 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC replace.

[0349] In some embodiments, R TA is phenyl or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is replaced by r 3 R TC In some embodiments, R TA is a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC In some embodiments, R TAis naphthyl or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC In some embodiments, R TA is a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring, or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC replace.

[0350] In some embodiments, R TA is phenyl or a 3-7 membered saturated or partially unsaturated monocyclic carbon ring; each of which is r 3 R TC In some embodiments, R TA is naphthyl or a 5-12 membered saturated or partially unsaturated bicyclic carbon ring; each of which is r 3 R TC In some embodiments, R TA is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC In some embodiments, R TA is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC replace.

[0351] In some embodiments, R TA It is C 1-6 aliphatic chain; a 3-7 membered saturated or partially unsaturated monocyclic carbocycle; a 5-12 membered saturated or partially unsaturated bicyclic carbocycle; a 3-7 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC In some embodiments, R TA It is C 1-6 Aliphatic chain; phenyl; naphthyl; 3-7 membered saturated or partially unsaturated monocyclic carbon ring; or 5-12 membered saturated or partially unsaturated bicyclic carbon ring; each of which is r 3 R TC In some embodiments, R TA It is C1-6 aliphatic chain; phenyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC replace.

[0352] In some embodiments, R TA It is C 1-6 aliphatic chain, a 3-7 membered saturated or partially unsaturated monocyclic carbon ring, or a 5-12 membered saturated or partially unsaturated bicyclic carbon ring; each of which is r 3 R TC In some embodiments, R TA It is C 1-6 an aliphatic chain, a 3-7 membered saturated or partially unsaturated monocyclic carbon ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 3 R TC In some embodiments, R TA It is C 1-6 Aliphatic chain, phenyl or 3-7 membered saturated or partially unsaturated monocyclic carbon ring; each of which is r 3 R TC replace.

[0353] In some embodiments, R TA is a group selected from the compounds described in Table 1.

[0354] As generally defined above, each R L Independently 4 R LC Replaced R A or R B In some embodiments, each R L Independently R A In some embodiments, each R L Independently 4 R LC Replaced R B .

[0355] In some embodiments, R LIs 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.

[0356] In some embodiments, R L Is oxo, halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, - OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0357] In some embodiments, R L In some embodiments, R L In some embodiments, R L In some embodiments, R L In some embodiments, R L In some embodiments, R L In some embodiments, R L In some embodiments, R L In some embodiments, R L In some embodiments, R L is -S(O)2F. In some embodiments, R L is -S(O)R. In some embodiments, R L is -S(O)NR2. In some embodiments, R L is -S(O)(NR)R. In some embodiments, R L is -C(O)R. In some embodiments, R LIn some embodiments, R L In some embodiments, R L is -C(O)N(R)OR. In some embodiments, R L is -OC(O)R. In some embodiments, R L In some embodiments, R L is -N(R)C(O)OR. In some embodiments, R L is -N(R)C(O)R. In some embodiments, R L is -N(R)C(O)NR2. In some embodiments, R L is -N(R)C(NR)NR2. In some embodiments, R L is -N(R)S(O)2NR2. In some embodiments, R L is -N(R)S(O)2R. In some embodiments, R L is -P(O)R2. In some embodiments, R L is -P(O)(R)OR. In some embodiments, R L is -B(OR)2. In some embodiments, R L It's deuterium.

[0358] In some embodiments, R L Is halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC (O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0359] In some embodiments, R L is halogen, -CN or -NO2. In some embodiments, R L Is -OR, -SR or -NR2. In some embodiments, R L In some embodiments, R L is -C(O)R, -C(O)OR, -C(O)NR2 or -C(O)N(R)OR. In some embodiments, RL Is -OC(O)R or -OC(O)NR2. In some embodiments, R L In some embodiments, R L It is -P(O)R2 or -P(O)(R)OR.

[0360] In some embodiments, R L is -OR, -OC(O)R or -OC(O)NR2. In some embodiments, R L 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.

[0361] In some embodiments, R L is -S(O)2R, -S(O)2NR2 or -S(O)2F. In some embodiments, R L is -S(O)R, -S(O)NR2 or -S(O)(NR)R. In some embodiments, R L Is -SR, -S(O)2R or -S(O)R. In some embodiments, R L is -S(O)2NR2, -S(O)NR2 or -S(O)(NR)R. In some embodiments, R L Is -S(O)2NR2 or -S(O)NR2. In some embodiments, R L It is -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0362] In some embodiments, R L is -N(R)C(O)OR, -N(R)C(O)R or -N(R)C(O)NR2. In some embodiments, R L is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R L is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R L is -N(R)C(O)NR2 or -N(R)S(O)2NR2. In some embodiments, R LIt is -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0363] In some embodiments, R L is -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)C(O)NR2. In some embodiments, R L is -NR2, -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R L It is -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0364] In some embodiments, R L It is C 1-6 aliphatic chain; phenyl; naphthyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is replaced by r 4 R LC replace.

[0365] In some embodiments, R L is r 4 R LC Substituted C 1-6 In some embodiments, R L is r 4 R LC In some embodiments, R L is r 4 R LC In some embodiments, R L is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r 4 R LC In some embodiments, R L is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r 4 R LC In some embodiments, R L is r 4 R LCsubstituted 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring. L is r 4 R LC In some embodiments, R L is a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r 4 R LC In some embodiments, R L is a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r 4 R LC replace.

[0366] In some embodiments, R L is phenyl; naphthyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is replaced by r 4 R LC replace.

[0367] In some embodiments, R L is phenyl; naphthyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 4 R LC In some embodiments, R L is a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 4 R LC replace.

[0368] In some embodiments, R L is phenyl; naphthyl; 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; or 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; each of which is r 4R LC In some embodiments, R L is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is replaced by 4 R LC replace.

[0369] In some embodiments, R L is phenyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 4 R LC In some embodiments, R L is naphthyl; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 4 R LC replace.

[0370] In some embodiments, R L is phenyl or naphthyl; each of which is r 4 R LC In some embodiments, R L is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 4 R LC In some embodiments, R L is a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; each of which is r 4 R LC In some embodiments, R L is a 3-7 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 4 R LC replace.

[0371] In some embodiments, R L is phenyl or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is replaced by r 4 R LC In some embodiments, R L is a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 4 R LC In some embodiments, R L is naphthyl or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 4 R LC In some embodiments, R L is a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring, or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 4 R LC replace.

[0372] In some embodiments, R L is phenyl or a 3-7 membered saturated or partially unsaturated monocyclic carbon ring; each of which is r 4 R LC In some embodiments, R L is naphthyl or a 5-12 membered saturated or partially unsaturated bicyclic carbon ring; each of which is r 4 R LC In some embodiments, R L is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 4 R LC In some embodiments, R L is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 4 R LC replace.

[0373] In some embodiments, R L It is C 1-6aliphatic chain; a 3-7 membered saturated or partially unsaturated monocyclic carbocycle; a 5-12 membered saturated or partially unsaturated bicyclic carbocycle; a 3-7 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 4 R LC In some embodiments, R L It is C 1-6 Aliphatic chain; phenyl; naphthyl; 3-7 membered saturated or partially unsaturated monocyclic carbon ring; or 5-12 membered saturated or partially unsaturated bicyclic carbon ring; each of which is r 4 R LC In some embodiments, R L It is C 1-6 aliphatic chain; phenyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 4 R LC replace.

[0374] In some embodiments, R L It is C 1-6 aliphatic chain, a 3-7 membered saturated or partially unsaturated monocyclic carbon ring, or a 5-12 membered saturated or partially unsaturated bicyclic carbon ring; each of which is r 4 R LC In some embodiments, R L It is C 1-6 an aliphatic chain, a 3-7 membered saturated or partially unsaturated monocyclic carbon ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; each of which is r 4 R LC In some embodiments, R L It is C 1-6 Aliphatic chain, phenyl or 3-7 membered saturated or partially unsaturated monocyclic carbon ring; each of which is r 4 R LC replace.

[0375] In some embodiments, R L is a group selected from the compounds described in Table 1.

[0376] As generally defined above, R Aand -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR).

[0377] In some embodiments, R A -C(O)R, -C(O)OR, -C(O)NR, -C(O)N(R)OR, -OC(O)R, -OC(O)NR, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR).

[0378] In some embodiments, R A In some embodiments, R A In some embodiments, R A In some embodiments, R A In some embodiments, R A In some embodiments, R A In some embodiments, R A In some embodiments, R A In some embodiments, R A is -S(O)2R. In some embodiments, R A In some embodiments, R A is -S(O)2F. In some embodiments, R A is -S(O)R. In some embodiments, R A is -S(O)NR2. In some embodiments, R A is -S(O)(NR)R. In some embodiments, RA is -C(O)R. In some embodiments, R A In some embodiments, R A In some embodiments, R A is -C(O)N(R)OR. In some embodiments, R A is -OC(O)R. In some embodiments, R A In some embodiments, R A is -N(R)C(O)OR. In some embodiments, R A is -N(R)C(O)R. In some embodiments, R A is -N(R)C(O)NR2. In some embodiments, R A is -N(R)C(NR)NR2. In some embodiments, R A is -N(R)S(O)2NR2. In some embodiments, R A is -N(R)S(O)2R. In some embodiments, R A is -P(O)R2. In some embodiments, R A is -P(O)(R)OR. In some embodiments, R A is -B(OR)2. In some embodiments, R A It's deuterium.

[0379] In some embodiments, R A Is halogen, -CN, -NO2, -OR, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC (O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)C(NR)NR2, -N(R)S(O)2NR2, -N(R)S(O)2R, -P(O)R2, -P(O)(R)OR, or -B(OR)2.

[0380] In some embodiments, R A is halogen, -CN or -NO2. In some embodiments, R A Is -OR, -SR or -NR2. In some embodiments, R A In some embodiments, R Ais -C(O)R, -C(O)OR, -C(O)NR2 or -C(O)N(R)OR. In some embodiments, R A Is -OC(O)R or -OC(O)NR2. In some embodiments, R A In some embodiments, R A It is -P(O)R2 or -P(O)(R)OR.

[0381] In some embodiments, R A is -OR, -OC(O)R or -OC(O)NR2. In some embodiments, R A 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.

[0382] In some embodiments, R A is -S(O)2R, -S(O)2NR2 or -S(O)2F. In some embodiments, R A is -S(O)R, -S(O)NR2 or -S(O)(NR)R. In some embodiments, R A Is -SR, -S(O)2R or -S(O)R. In some embodiments, R A is -S(O)2NR2, -S(O)NR2 or -S(O)(NR)R. In some embodiments, R A Is -S(O)2NR2 or -S(O)NR2. In some embodiments, R A It is -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0383] In some embodiments, R A is -N(R)C(O)OR, -N(R)C(O)R or -N(R)C(O)NR2. In some embodiments, R A is -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R A is -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R Ais -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.

[0384] In some embodiments, R A is -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)C(O)NR2. In some embodiments, R A is -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.

[0385] In some embodiments, R A is a group selected from the compounds described in Table 1.

[0386] As generally defined above, R B In each case, independently C 1-6 aliphatic chain; phenyl; naphthyl; cubanyl; adamantyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocycle; a 5-12 membered saturated or partially unsaturated bicyclic carbocycle; a 3-7 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0387] In some embodiments, R B It is C 1-6 In some embodiments, R B In some embodiments, R B In some embodiments, R B In some embodiments, R B In some embodiments, R B is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur. In some embodiments, R B is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur. In some embodiments, R B is a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring. Bis a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring. B is a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. B is a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0388] In some embodiments, R B is phenyl; naphthyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0389] In some embodiments, R B is phenyl; naphthyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur. In some embodiments, R B is a 3-7 membered saturated or partially unsaturated monocyclic carbocycle; a 5-12 membered saturated or partially unsaturated bicyclic carbocycle; a 3-7 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0390] In some embodiments, R B is phenyl; naphthyl; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring. In some embodiments, R B is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0391] In some embodiments, R Bis phenyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. In some embodiments, R B is naphthyl; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0392] In some embodiments, R B is phenyl or naphthyl. In some embodiments, R B is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur. In some embodiments, R B is a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring. B is a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0393] In some embodiments, R B is phenyl or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur. In some embodiments, R B is a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. B is naphthyl or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur. In some embodiments, R B is a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring, or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0394] In some embodiments, R B is phenyl or a 3-7 membered saturated or partially unsaturated monocyclic carbon ring. B is naphthyl or a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring. Bis a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. In some embodiments, R B is an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0395] In some embodiments, R B It is C 1-6 aliphatic chain; a 3-7 membered saturated or partially unsaturated monocyclic carbocycle; a 5-12 membered saturated or partially unsaturated bicyclic carbocycle; a 3-7 membered saturated or partially unsaturated monocyclic heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocycle having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur. In some embodiments, R B It is C 1-6 aliphatic chain; phenyl; naphthyl; 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; or 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring. In some embodiments, R B It is C 1-6 an aliphatic chain; a phenyl group; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0396] In some embodiments, R B It is C 1-6 aliphatic chain, a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring. B It is C 1-6 an aliphatic chain, a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. B It is C 1-6 Aliphatic chain, phenyl or 3-7 membered saturated or partially unsaturated monocyclic carbon ring.

[0397] In some embodiments, R B is a group selected from the compounds described in Table 1.

[0398] As generally defined above, R 1Cwherein each occurrence is independently oxo, deuterium, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0399] In some embodiments, R 1C wherein each occurrence is independently oxo, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0400] In some embodiments, R 1C-C(O)R, -C(O)OR, -C(O)NR, -C(O)N(R)OR, -OC(O)R, -OC(O)NR, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR). In some embodiments, R 1C is independently in each case an optionally substituted group selected from the group consisting of: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0401] In some embodiments, R 1C In some embodiments, R 1C In some embodiments, R 1C In some embodiments, R 1C In some embodiments, R 1C In some embodiments, R 1C In some embodiments, R 1C In some embodiments, R 1C In some embodiments, R 1C In some embodiments, R 1C In some embodiments, R 1C is -S(O)2F. In some embodiments, R 1C is -S(O)R. In some embodiments, R 1C is -S(O)NR2. In some embodiments, R 1C is -S(O)(NR)R. In some embodiments, R 1C is -C(O)R. In some embodiments, R 1C In some embodiments, R 1C In some embodiments, R 1C is -C(O)N(R)OR. In some embodiments, R 1C is -OC(O)R. In some embodiments, R1C In some embodiments, R 1C is -N(R)C(O)OR. In some embodiments, R 1C is -N(R)C(O)R. In some embodiments, R 1C is -N(R)C(O)NR2. In some embodiments, R 1C is -N(R)C(NR)NR2. In some embodiments, R 1C is -N(R)S(O)2NR2. In some embodiments, R 1C is -N(R)S(O)2R. In some embodiments, R 1C is -P(O)R2. In some embodiments, R 1C is -P(O)(R)OR. In some embodiments, R 1C It is -B(OR)2.

[0402] In some embodiments, R 1C -C(O)R, -C(O)OR, -C(O)NR, -C(O)N(R)OR, -OC(O)R, -OC(O)NR, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR).

[0403] In some embodiments, R 1C In some embodiments, R 1C In some embodiments, R 1C In some embodiments, R 1C In some embodiments, R 1C In each case, R is independently -OC(O)R or -OC(O)NR2. 1CIn some embodiments, R 1C Each occurrence is independently -P(O)R2 or -P(O)(R)OR.

[0404] In some embodiments, R 1C In some embodiments, R 1C In some embodiments, R 1C Each occurrence 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.

[0405] In some embodiments, R 1C In each case, R is independently -S(O)2R, -S(O)2NR2, or -S(O)2F. 1C In some embodiments, R 1C Each occurrence is independently -SR, -S(O)2R, or -S(O)R. In some embodiments, R 1C In some embodiments, R 1C In each case, R is independently -S(O)2NR2 or -S(O)NR2. 1C Each occurrence is independently -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0406] In some embodiments, R 1C In some embodiments, R 1C Each occurrence is independently -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R 1CEach occurrence is independently -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R 1C In each case, R is independently -N(R)C(O)NR2 or -N(R)S(O)2NR2. 1C and -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0407] In some embodiments, R 1C In some embodiments, R 1C Each occurrence is independently -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R 1C Each occurrence is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0408] In some embodiments, R 1C is independently at each occurrence an optionally substituted C 1-6 In some embodiments, R 1C In some embodiments, R 1C is independently in each case an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. 1C Each occurrence is independently an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0409] In some embodiments, R 1C is independently at each occurrence an optionally substituted C 1-6 aliphatic, or an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. 1C Each occurrence is independently optionally substituted phenyl, or an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0410] In some embodiments, R 1C is independently at each occurrence an optionally substituted C 1-6 aliphatic or optionally substituted phenyl. In some embodiments, R 1CIn each occurrence is independently an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0411] In some embodiments, R 1C is independently at each occurrence an optionally substituted group selected from phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0412] In some embodiments, R 1C In each case, independently C 1-6 In some embodiments, R 1C In some embodiments, R 1C is independently in each occurrence a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. In some embodiments, R 1C Each occurrence is independently a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0413] In some embodiments, R 1C In each case, independently C 1-6 aliphatic, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. 1C Each occurrence is independently phenyl or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0414] In some embodiments, R 1C In each case, independently C 1-6 In some embodiments, R 1C Each occurrence is independently a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0415] In some embodiments, R 1C Each occurrence is independently phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0416] In some embodiments, R 1C is independently halogen, -CN, -O-(optionally substituted C 1-6 aliphatic) or an optionally substituted C 1-6 In some embodiments, R 1C is independently at each occurrence halogen, -CN, -O-(C 1-6 Aliphatic) or C 1-6 aliphatic group; wherein each C 1-6 The aliphatic group is optionally substituted with one or more halogen atoms. 1C is independently halogen or C optionally substituted with 1-3 halogens at each occurrence 1-3 In some embodiments, R 1C is independently in each instance fluoro, chloro, -CH3, -CHF2 or -CF3.

[0417] In some embodiments, R 1C wherein each occurrence is independently oxo, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or optionally substituted C(O) or C(O) 1-6 Aliphatic group.

[0418] In some embodiments, R 1C is independently in each case selected from the groups depicted in the compounds in Table 1.

[0419] As generally defined above, R 2Cwherein each occurrence is independently oxo, deuterium, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0420] In some embodiments, R 2C wherein each occurrence is independently oxo, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0421] In some embodiments, R 2C-C(O)R, -C(O)OR, -C(O)NR, -C(O)N(R)OR, -OC(O)R, -OC(O)NR, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR). In some embodiments, R 2C is independently in each case an optionally substituted group selected from the group consisting of: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0422] In some embodiments, R 2C In some embodiments, R 2C In some embodiments, R 2C In some embodiments, R 2C In some embodiments, R 2C In some embodiments, R 2C In some embodiments, R 2C In some embodiments, R 2C In some embodiments, R 2C In some embodiments, R 2C In some embodiments, R 2C is -S(O)2F. In some embodiments, R 2C is -S(O)R. In some embodiments, R 2C is -S(O)NR2. In some embodiments, R 2C is -S(O)(NR)R. In some embodiments, R 2C is -C(O)R. In some embodiments, R 2C In some embodiments, R 2C In some embodiments, R 2C is -C(O)N(R)OR. In some embodiments, R 2C is -OC(O)R. In some embodiments, R2C In some embodiments, R 2C is -N(R)C(O)OR. In some embodiments, R 2C is -N(R)C(O)R. In some embodiments, R 2C is -N(R)C(O)NR2. In some embodiments, R 2C is -N(R)C(NR)NR2. In some embodiments, R 2C is -N(R)S(O)2NR2. In some embodiments, R 2C is -N(R)S(O)2R. In some embodiments, R 2C is -P(O)R2. In some embodiments, R 2C is -P(O)(R)OR. In some embodiments, R 2C It is -B(OR)2.

[0423] In some embodiments, R 2C -C(O)R, -C(O)OR, -C(O)NR, -C(O)N(R)OR, -OC(O)R, -OC(O)NR, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR).

[0424] In some embodiments, R 2C In some embodiments, R 2C In some embodiments, R 2C In some embodiments, R 2C In some embodiments, R 2C In each case, R is independently -OC(O)R or -OC(O)NR2. 2CIn some embodiments, R 2C Each occurrence is independently -P(O)R2 or -P(O)(R)OR.

[0425] In some embodiments, R 2C In some embodiments, R 2C In some embodiments, R 2C Each occurrence 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.

[0426] In some embodiments, R 2C In each case, R is independently -S(O)2R, -S(O)2NR2, or -S(O)2F. 2C In some embodiments, R 2C Each occurrence is independently -SR, -S(O)2R, or -S(O)R. In some embodiments, R 2C In some embodiments, R 2C In each case, R is independently -S(O)2NR2 or -S(O)NR2. 2C Each occurrence is independently -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0427] In some embodiments, R 2C In some embodiments, R 2C Each occurrence is independently -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R 2CEach occurrence is independently -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R 2C In each case, R is independently -N(R)C(O)NR2 or -N(R)S(O)2NR2. 2C and -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0428] In some embodiments, R 2C In some embodiments, R 2C In some embodiments, R 2C Each occurrence is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0429] In some embodiments, R 2C is independently at each occurrence an optionally substituted C 1-6 In some embodiments, R 2C In some embodiments, R 2C is independently in each case an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. 2C Each occurrence is independently an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0430] In some embodiments, R 2C is independently at each occurrence an optionally substituted C 1-6 aliphatic, or an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. 2C Each occurrence is independently optionally substituted phenyl, or an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0431] In some embodiments, R 2C is independently at each occurrence an optionally substituted C 1-6 aliphatic or optionally substituted phenyl. In some embodiments, R 2CIn each occurrence is independently an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0432] In some embodiments, R 2C is independently at each occurrence an optionally substituted group selected from phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0433] In some embodiments, R 2C In each case, independently C 1-6 In some embodiments, R 2C In some embodiments, R 2C is independently in each occurrence a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. In some embodiments, R 2C Each occurrence is independently a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0434] In some embodiments, R 2C In each case, independently C 1-6 aliphatic, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. 2C Each occurrence is independently phenyl, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0435] In some embodiments, R 2C In each case, independently C 1-6 In some embodiments, R 2C Each occurrence is independently a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0436] In some embodiments, R 2C Each occurrence is independently phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0437] In some embodiments, R 2C is independently halogen, -CN, -O-(optionally substituted C 1-6 aliphatic) or an optionally substituted C 1-6 In some embodiments, R 2C is independently at each occurrence halogen, -CN, -O-(C 1-6 Aliphatic) or C 1-6 aliphatic group; wherein each C 1-6 The aliphatic group is optionally substituted with one or more halogen atoms. 2C is independently halogen or C optionally substituted with 1-3 halogens at each occurrence 1-3 In some embodiments, R 2C is independently in each instance fluoro, chloro, -CH3, -CHF2 or -CF3.

[0438] In some embodiments, R 2C wherein each occurrence is independently oxo, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or optionally substituted C(O) or C(O) 1-6 Aliphatic group.

[0439] In some embodiments, R 2C In each case, independently C 1-6 aliphatic, which is optionally substituted by: (i) 1 or 2 independently selected from -O-(C 1-6 Aliphatic), -OH, -N(C 1-6 and (ii) 1, 2 or 3 atoms independently selected from halogen and deuterium. In some embodiments, R 2C In each case, independently C 1-6 aliphatic, which is optionally substituted by: (i) 1 or 2 independently selected from -O-(C 1-6 Aliphatic), -OH, -N(C 1-6 In some embodiments, R2C In each case, independently C 1-6 aliphatic, which is optionally substituted by 1 or 2 independently selected from -O-(C 1-6 Aliphatic), -OH, -N(C 1-6 In some embodiments, R 2C In each case, independently C 1-6 aliphatic, which is optionally substituted by 1, 2 or 3 atoms independently selected from halogen and deuterium. In some embodiments, R 2C In each case, independently C 1-6 Aliphatic groups are optionally substituted with 1, 2 or 3 atoms independently selected from halogen.

[0440] In some embodiments, R 2C is independently at each occurrence oxo, deuterium, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 The aliphatic group is optionally substituted with one or more halogen atoms. 2C is independently oxo, deuterium, halogen, or -CN at each occurrence. In some embodiments, R 2C is independently oxo, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 The aliphatic group is optionally substituted with one or more halogen atoms. 2C is independently in each case -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 The aliphatic group is optionally substituted with one or more halogen atoms. 2C is independently in each case -O-(C 1-3 Aliphatic) or C 1-3 Aliphatic group.

[0441] In some embodiments, R 2C is independently in each case selected from the groups depicted in the compounds in Table 1.

[0442] As generally defined above, R TCwherein each occurrence is independently oxo, deuterium, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0443] In some embodiments, R TC wherein each occurrence is independently oxo, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0444] In some embodiments, R TC-C(O)R, -C(O)OR, -C(O)NR, -C(O)N(R)OR, -OC(O)R, -OC(O)NR, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR). In some embodiments, R TC is independently in each case an optionally substituted group selected from the group consisting of: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0445] In some embodiments, R TC In some embodiments, R TC In some embodiments, R TC In some embodiments, R TC In some embodiments, R TC In some embodiments, R TC In some embodiments, R TC In some embodiments, R TC In some embodiments, R TC In some embodiments, R TC In some embodiments, R TC is -S(O)2F. In some embodiments, R TC is -S(O)R. In some embodiments, R TC is -S(O)NR2. In some embodiments, R TC is -S(O)(NR)R. In some embodiments, R TC is -C(O)R. In some embodiments, R TC In some embodiments, R TC In some embodiments, R TC is -C(O)N(R)OR. In some embodiments, R TC is -OC(O)R. In some embodiments, RTC In some embodiments, R TC is -N(R)C(O)OR. In some embodiments, R TC is -N(R)C(O)R. In some embodiments, R TC is -N(R)C(O)NR2. In some embodiments, R TC is -N(R)C(NR)NR2. In some embodiments, R TC is -N(R)S(O)2NR2. In some embodiments, R TC is -N(R)S(O)2R. In some embodiments, R TC is -P(O)R2. In some embodiments, R TC is -P(O)(R)OR. In some embodiments, R TC It is -B(OR)2.

[0446] In some embodiments, R TC -C(O)R, -C(O)OR, -C(O)NR, -C(O)N(R)OR, -OC(O)R, -OC(O)NR, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR).

[0447] In some embodiments, R TC In some embodiments, R TC In some embodiments, R TC In some embodiments, R TC In some embodiments, R TC In each case, R is independently -OC(O)R or -OC(O)NR2. TCIn some embodiments, R TC Each occurrence is independently -P(O)R2 or -P(O)(R)OR.

[0448] In some embodiments, R TC In some embodiments, R TC Each occurrence is independently -SR, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, or -S(O)(NR)R. In some embodiments, R TC Each occurrence 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.

[0449] In some embodiments, RT C In each case, R is independently -S(O)2R, -S(O)2NR2, or -S(O)2F. TC In some embodiments, R TC Each occurrence is independently -SR, -S(O)2R, or -S(O)R. In some embodiments, R TC In some embodiments, R TC In each case, R is independently -S(O)2NR2 or -S(O)NR2. TC Each occurrence is independently -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0450] In some embodiments, R TC In some embodiments, R TC In each case, R is independently -N(R)S(O)2NR2 or -N(R)S(O)2R. TCEach occurrence is independently -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R TC In each case, R is independently -N(R)C(O)NR2 or -N(R)S(O)2NR2. TC and -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0451] In some embodiments, R TC In some embodiments, R TC In some embodiments, R TC Each occurrence is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0452] In some embodiments, R TC is independently at each occurrence an optionally substituted C 1-6 In some embodiments, R TC In some embodiments, R TC is independently in each case an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. TC Each occurrence is independently an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0453] In some embodiments, R TC is independently at each occurrence an optionally substituted C 1-6 aliphatic, or an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. TC Each occurrence is independently optionally substituted phenyl, or an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0454] In some embodiments, R TC is independently at each occurrence an optionally substituted C 1-6 aliphatic or optionally substituted phenyl. In some embodiments, R TCIn each occurrence is independently an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0455] In some embodiments, R TC is independently at each occurrence an optionally substituted group selected from phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0456] In some embodiments, R TC In each case, independently C 1-6 In some embodiments, R TC In some embodiments, R TC is independently in each occurrence a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. In some embodiments, R TC Each occurrence is independently a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0457] In some embodiments, R TC In each case, independently C 1-6 aliphatic, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. TC Each occurrence is independently phenyl or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0458] In some embodiments, R TC In each case, independently C 1-6 In some embodiments, R TC Each occurrence is independently a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0459] In some embodiments, R TC Each occurrence is independently phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0460] In some embodiments, R TC is independently halogen, -CN, -O-(optionally substituted C 1-6 aliphatic) or an optionally substituted C 1-6 In some embodiments, R TC is independently at each occurrence halogen, -CN, -O-(C 1-6 Aliphatic) or C 1-6 aliphatic group; wherein each C 1-6 The aliphatic group is optionally substituted with one or more halogen atoms. TC is independently halogen or C optionally substituted with 1-3 halogens at each occurrence 1-3 In some embodiments, R TC is independently in each instance fluoro, chloro, -CH3, -CHF2 or -CF3.

[0461] In some embodiments, R TC In each case it is C 1-6 aliphatic, which is optionally substituted by: (i) 1 or 2 independently selected from -O-(C 1-6 Aliphatic), -OH, -N(C 1-6 and (ii) 1, 2 or 3 atoms independently selected from halogen and deuterium. In some embodiments, R TC In each case it is C 1-6 aliphatic, which is optionally substituted by: (i) 1 or 2 independently selected from -O-(C 1-6 Aliphatic), -OH, -N(C 1-6 In some embodiments, R TC In each case it is C 1-6 aliphatic, which is optionally substituted by 1 or 2 groups independently selected from: -O-(C 1-6 Aliphatic), -OH, -N(C 1-6 In some embodiments, R TC In each case it is C 1-6 aliphatic, which is optionally substituted by 1, 2 or 3 atoms independently selected from halogen and deuterium. In some embodiments, R TC In each case it is C 1-6 Aliphatic groups are optionally substituted with 1, 2 or 3 atoms independently selected from halogen.

[0462] In some embodiments, R TCis independently at each occurrence oxo, deuterium, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 The aliphatic group is optionally substituted with one or more halogen atoms. TC is independently oxo, deuterium, halogen, or -CN at each occurrence. In some embodiments, R TC is independently oxo, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 The aliphatic group is optionally substituted with one or more halogen atoms. TC is independently in each case -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 The aliphatic group is optionally substituted with one or more halogen atoms. TC is independently in each case -O-(C 1-3 Aliphatic) or C 1-3 Aliphatic group.

[0463] In some embodiments, R TC is independently at each occurrence halogen, -CN, -OH, -O-(optionally substituted C 1-3 aliphatic) or an optionally substituted C 1-3 In some embodiments, R TC is independently at each occurrence halogen, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 Aliphatic groups are optionally substituted with 1-3 halogens. TC In some embodiments, R TC is independently in each instance fluoro or -OH.

[0464] In some embodiments, R TC is independently at each occurrence oxo, deuterium, halogen, -CN, -OH, -O-(optionally substituted C 1-3 aliphatic) or an optionally substituted C 1-3 In some embodiments, R TC is independently at each occurrence oxo, deuterium, halogen, -CN, -OH, -O-(C 1-3Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 The aliphatic group is optionally substituted with one or more halogen atoms. TC is independently at each occurrence oxo, deuterium, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 Aliphatic groups are optionally substituted with 1-3 halogens. TC In some embodiments, R TC In some embodiments, R TC is independently oxo, deuterium, -CN, -CH3, or -CHF2 at each occurrence. In some embodiments, R TC is independently in each instance deuterium, -CN, -CH3 or -CHF2.

[0465] In some embodiments, R TC is independently at each occurrence oxo, halogen, -CN, -OH, -O-(optionally substituted C 1-3 aliphatic) or an optionally substituted C 1-3 In some embodiments, R TC is independently at each occurrence oxo, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 The aliphatic group is optionally substituted with one or more halogen atoms. TC is independently at each occurrence oxo, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 Aliphatic groups are optionally substituted with 1-3 halogens. TC In some embodiments, R TC In some embodiments, R TC In some embodiments, R TCis independently in each instance -CN, -CH3 or -CHF2.

[0466] In some embodiments, R TC is independently in each case selected from the groups depicted in the compounds in Table 1.

[0467] As generally defined above, R TTC wherein each occurrence is independently oxo, deuterium, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0468] In some embodiments, R TTC wherein each occurrence is independently oxo, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0469] In some embodiments, R TTC-C(O)R, -C(O)OR, -C(O)NR, -C(O)N(R)OR, -OC(O)R, -OC(O)NR, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR). In some embodiments, R TTC is independently in each case an optionally substituted group selected from the group consisting of: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0470] In some embodiments, R TTC In some embodiments, R TTC In some embodiments, R TTC In some embodiments, R TTC In some embodiments, R TTC In some embodiments, R TTC In some embodiments, R TTC In some embodiments, R TTC In some embodiments, R TTC is -S(O)2R. In some embodiments, R TTC In some embodiments, R TTC is -S(O)2F. In some embodiments, R TTC is -S(O)R. In some embodiments, R TTC is -S(O)NR2. In some embodiments, R TTC is -S(O)(NR)R. In some embodiments, R TTC is -C(O)R. In some embodiments, R TTC In some embodiments, R TTC In some embodiments, R TTC is -C(O)N(R)OR. In some embodiments, R TTC is -OC(O)R. In some embodiments, RTTC In some embodiments, R TTC is -N(R)C(O)OR. In some embodiments, R TTC is -N(R)C(O)R. In some embodiments, R TTC is -N(R)C(O)NR2. In some embodiments, R TTC is -N(R)C(NR)NR2. In some embodiments, R TTC is -N(R)S(O)2NR2. In some embodiments, R TTC is -N(R)S(O)2R. In some embodiments, R TTC is -P(O)R2. In some embodiments, R TTC is -P(O)(R)OR. In some embodiments, R TTC It is -B(OR)2.

[0471] In some embodiments, R TTC -C(O)R, -C(O)OR, -C(O)NR, -C(O)N(R)OR, -OC(O)R, -OC(O)NR, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR).

[0472] In some embodiments, R TTC In some embodiments, R TTC In some embodiments, R TTC In some embodiments, R TTC In some embodiments, R TTC In each case, R is independently -OC(O)R or -OC(O)NR2. TTCIn some embodiments, R TTC Each occurrence is independently -P(O)R2 or -P(O)(R)OR.

[0473] In some embodiments, R TTC In some embodiments, R TTC In some embodiments, R TTC Each occurrence 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.

[0474] In some embodiments, R TTC In each case, R is independently -S(O)2R, -S(O)2NR2, or -S(O)2F. TTC In some embodiments, R TTC Each occurrence is independently -SR, -S(O)2R, or -S(O)R. In some embodiments, R TTC In some embodiments, R TTC In each case, R is independently -S(O)2NR2 or -S(O)NR2. TTC Each occurrence is independently -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0475] In some embodiments, R TTC In some embodiments, R TTC Each occurrence is independently -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R TTCEach occurrence is independently -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R TTC In each case, R is independently -N(R)C(O)NR2 or -N(R)S(O)2NR2. TTC and -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0476] In some embodiments, R TTC In some embodiments, R TTC In some embodiments, R TTC Each occurrence is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0477] In some embodiments, R TTC is independently at each occurrence an optionally substituted C 1-6 In some embodiments, R TTC In some embodiments, R TTC is independently in each case an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. TTC Each occurrence is independently an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0478] In some embodiments, R TTC is independently at each occurrence an optionally substituted C 1-6 aliphatic, or an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. TTC Each occurrence is independently optionally substituted phenyl, or an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0479] In some embodiments, R TTC is independently at each occurrence an optionally substituted C 1-6 aliphatic or optionally substituted phenyl. In some embodiments, R TTCIn each occurrence is independently an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0480] In some embodiments, R TTC is independently at each occurrence an optionally substituted group selected from phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0481] In some embodiments, R TTC In each case, independently C 1-6 In some embodiments, R TTC In some embodiments, R TTC is independently in each occurrence a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. In some embodiments, R TTC Each occurrence is independently a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0482] In some embodiments, R TTC In each case, independently C 1-6 aliphatic, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. TTC Each occurrence is independently phenyl, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0483] In some embodiments, R TTC In each case, independently C 1-6 In some embodiments, R TTC Each occurrence is independently a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0484] In some embodiments, R TTC Each occurrence is independently phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0485] In some embodiments, R TTC wherein each occurrence is independently oxo, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or optionally substituted C(O) or C(O) 1-6 Aliphatic group.

[0486] In some embodiments, R TTC is independently at each occurrence halogen, -CN, -OH, -O-(optionally substituted C 1-3 aliphatic) or an optionally substituted C 1-3 In some embodiments, R TTC is independently at each occurrence halogen, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 Aliphatic groups are optionally substituted with 1-3 halogens. TTC In some embodiments, R TTC is independently in each instance fluoro or -OH.

[0487] In some embodiments, R TTC is independently at each occurrence oxo, deuterium, halogen, -CN, -OH, -O-(optionally substituted C 1-3 aliphatic) or an optionally substituted C 1-3 In some embodiments, R TTC is independently at each occurrence oxo, deuterium, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 The aliphatic group is optionally substituted with one or more halogen atoms. TTC is independently at each occurrence oxo, deuterium, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C1-3 Aliphatic groups are optionally substituted with 1-3 halogens. TTC In some embodiments, R TTC In some embodiments, R TTC is independently oxo, deuterium, -CN, -CH3, or -CHF2 at each occurrence. In some embodiments, R TTC is independently in each instance deuterium, -CN, -CH3 or -CHF2.

[0488] In some embodiments, R TTC is independently at each occurrence oxo, halogen, -CN, -OH, -O-(optionally substituted C 1-3 aliphatic) or an optionally substituted C 1-3 In some embodiments, R TTC is independently at each occurrence oxo, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 The aliphatic group is optionally substituted with one or more halogen atoms. TTC is independently at each occurrence oxo, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 Aliphatic groups are optionally substituted with 1-3 halogens. TTC In some embodiments, R TTC In some embodiments, R TTC In some embodiments, R TTC is independently in each instance -CN, -CH3 or -CHF2.

[0489] In some embodiments, R TTC is independently in each case selected from the groups depicted in the compounds in Table 1.

[0490] As generally defined above, R 11Cwherein each occurrence is independently oxo, deuterium, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0491] In some embodiments, R 11C wherein each occurrence is independently oxo, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0492] In some embodiments, R 11C-C(O)R, -C(O)OR, -C(O)NR, -C(O)N(R)OR, -OC(O)R, -OC(O)NR, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR). In some embodiments, R 11C is independently in each case an optionally substituted group selected from the group consisting of: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0493] In some embodiments, R 11C In some embodiments, R 11C In some embodiments, R 11C In some embodiments, R 11C In some embodiments, R 11C In some embodiments, R 11C In some embodiments, R 11C In some embodiments, R 11C In some embodiments, R 11C is -S(O)2R. In some embodiments, R 11C In some embodiments, R 11C is -S(O)2F. In some embodiments, R 11C is -S(O)R. In some embodiments, R 11C is -S(O)NR2. In some embodiments, R 11C is -S(O)(NR)R. In some embodiments, R 11C is -C(O)R. In some embodiments, R 11C In some embodiments, R 11C In some embodiments, R 11C is -C(O)N(R)OR. In some embodiments, R 11C is -OC(O)R. In some embodiments, R11C In some embodiments, R 11C is -N(R)C(O)OR. In some embodiments, R 11C is -N(R)C(O)R. In some embodiments, R 11C is -N(R)C(O)NR2. In some embodiments, R 11C is -N(R)C(NR)NR2. In some embodiments, R 11C is -N(R)S(O)2NR2. In some embodiments, R 11C is -N(R)S(O)2R. In some embodiments, R 11C is -P(O)R2. In some embodiments, R 11C is -P(O)(R)OR. In some embodiments, R 11C It is -B(OR)2.

[0494] In some embodiments, R 11C -C(O)R, -C(O)OR, -C(O)NR, -C(O)N(R)OR, -OC(O)R, -OC(O)NR, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR).

[0495] In some embodiments, R 11C In some embodiments, R 11C In some embodiments, R 11C In some embodiments, R 11C In some embodiments, R 11C In each case, R is independently -OC(O)R or -OC(O)NR2. 11CIn some embodiments, R 11C Each occurrence is independently -P(O)R2 or -P(O)(R)OR.

[0496] In some embodiments, R 11C In some embodiments, R 11C Each occurrence 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 11C Each occurrence 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.

[0497] In some embodiments, R 11C In each case, R is independently -S(O)2R, -S(O)2NR2, or -S(O)2F. 11C In some embodiments, R 11C Each occurrence is independently -SR, -S(O)2R, or -S(O)R. In some embodiments, R 11C In some embodiments, R 11C In each case, R is independently -S(O)2NR2 or -S(O)NR2. 11C Each occurrence is independently -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0498] In some embodiments, R 11C In some embodiments, R 11C In each case, R is independently -N(R)S(O)2NR2 or -N(R)S(O)2R. 11CEach occurrence is independently -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R 11C In each case, R is independently -N(R)C(O)NR2 or -N(R)S(O)2NR2. 11C and -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0499] In some embodiments, R 11C In some embodiments, R 11C In some embodiments, R 11C Each occurrence is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0500] In some embodiments, R 11C is independently at each occurrence an optionally substituted C 1-6 In some embodiments, R 11C In some embodiments, R 11C is independently in each case an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. 11C Each occurrence is independently an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0501] In some embodiments, R 11C is independently at each occurrence an optionally substituted C 1-6 aliphatic, or an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. 11C Each occurrence is independently optionally substituted phenyl, or an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0502] In some embodiments, R 11C is independently at each occurrence an optionally substituted C 1-6 aliphatic or optionally substituted phenyl. In some embodiments, R 11CIn each occurrence is independently an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0503] In some embodiments, R 11C is independently at each occurrence an optionally substituted group selected from phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0504] In some embodiments, R 11C In each case, independently C 1-6 In some embodiments, R 11C In some embodiments, R 11C is independently in each occurrence a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. In some embodiments, R 11C Each occurrence is independently a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0505] In some embodiments, R 11C In each case, independently C 1-6 aliphatic, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. 11C Each occurrence is independently phenyl, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0506] In some embodiments, R 11C In each case, independently C 1-6 In some embodiments, R 11C Each occurrence is independently a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0507] In some embodiments, R 11C Each occurrence is independently phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0508] In some embodiments, R 11C wherein each occurrence is independently oxo, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or optionally substituted C(O) or C(O) 1-6 Aliphatic group.

[0509] In some embodiments, R 11C is independently at each occurrence halogen, -CN, -OH, -O-(optionally substituted C 1-3 aliphatic) or an optionally substituted C 1-3 In some embodiments, R 11C is independently at each occurrence halogen, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 Aliphatic groups are optionally substituted with 1-3 halogens. 11C In some embodiments, R 11C is independently in each instance fluoro or -OH.

[0510] In some embodiments, R 11C is independently at each occurrence oxo, deuterium, halogen, -CN, -OH, -O-(optionally substituted C 1-3 aliphatic) or an optionally substituted C 1-3 In some embodiments, R 11C is independently at each occurrence oxo, deuterium, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 The aliphatic group is optionally substituted with one or more halogen atoms. 11C is independently at each occurrence oxo, deuterium, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C1-3 Aliphatic groups are optionally substituted with 1-3 halogens. 11C In some embodiments, R 11C In some embodiments, R 11C is independently oxo, deuterium, -CN, -CH3, or -CHF2 at each occurrence. In some embodiments, R 11C is independently in each instance deuterium, -CN, -CH3 or -CHF2.

[0511] In some embodiments, R 11C is independently at each occurrence oxo, halogen, -CN, -OH, -O-(optionally substituted C 1-3 aliphatic) or an optionally substituted C 1-3 In some embodiments, R 11C is independently at each occurrence oxo, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 The aliphatic group is optionally substituted with one or more halogen atoms. 11C is independently at each occurrence oxo, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 Aliphatic groups are optionally substituted with 1-3 halogens. 11C In some embodiments, R 11C In some embodiments, R 11C In some embodiments, R 11C is independently in each instance -CN, -CH3 or -CHF2.

[0512] In some embodiments, R 11C is independently in each case selected from the groups depicted in the compounds in Table 1.

[0513] As generally defined above, R 22Cwherein each occurrence is independently oxo, deuterium, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0514] In some embodiments, R 22C wherein each occurrence is independently oxo, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0515] In some embodiments, R 22C-C(O)R, -C(O)OR, -C(O)NR, -C(O)N(R)OR, -OC(O)R, -OC(O)NR, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR). In some embodiments, R 22C is independently in each case an optionally substituted group selected from the group consisting of: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0516] In some embodiments, R 22C In some embodiments, R 22C In some embodiments, R 22C In some embodiments, R 22C In some embodiments, R 22C In some embodiments, R 22C In some embodiments, R 22C In some embodiments, R 22C In some embodiments, R 22C In some embodiments, R 22C In some embodiments, R 22C is -S(O)2F. In some embodiments, R 22C is -S(O)R. In some embodiments, R 22C is -S(O)NR2. In some embodiments, R 22C is -S(O)(NR)R. In some embodiments, R 22C is -C(O)R. In some embodiments, R 22C In some embodiments, R 22C In some embodiments, R 22C is -C(O)N(R)OR. In some embodiments, R 22C is -OC(O)R. In some embodiments, R22C In some embodiments, R 22C is -N(R)C(O)OR. In some embodiments, R 22C Is -N(R)C(O)R. In some embodiments, R2 2C is -N(R)C(O)NR2. In some embodiments, R 22C is -N(R)C(NR)NR2. In some embodiments, R 22C is -N(R)S(O)2NR2. In some embodiments, R 22C is -N(R)S(O)2R. In some embodiments, R 22C is -P(O)R2. In some embodiments, R 22C is -P(O)(R)OR. In some embodiments, R 22C It is -B(OR)2.

[0517] In some embodiments, R 22C -C(O)R, -C(O)OR, -C(O)NR, -C(O)N(R)OR, -OC(O)R, -OC(O)NR, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR).

[0518] In some embodiments, R 22C In some embodiments, R 22C In some embodiments, R 22C In some embodiments, R 22C In some embodiments, R 22C In each case, R is independently -OC(O)R or -OC(O)NR2. 22CIn some embodiments, R 22C Each occurrence is independently -P(O)R2 or -P(O)(R)OR.

[0519] In some embodiments, R 22C In some embodiments, R 22C Each occurrence 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 22C Each occurrence 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.

[0520] In some embodiments, R 22C In each case, R is independently -S(O)2R, -S(O)2NR2, or -S(O)2F. 22C In some embodiments, R 22C Each occurrence is independently -SR, -S(O)2R, or -S(O)R. In some embodiments, R 22C In some embodiments, R 22C In each case, R is independently -S(O)2NR2 or -S(O)NR2. 22C Each occurrence is independently -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0521] In some embodiments, R 22C In some embodiments, R 22C In each case, R is independently -N(R)S(O)2NR2 or -N(R)S(O)2R. 22CEach occurrence is independently -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R 22C In each case, R is independently -N(R)C(O)NR2 or -N(R)S(O)2NR2. 22C and -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0522] In some embodiments, R 22C In some embodiments, R 22C Each occurrence is independently -NR2, -N(R)C(O)OR, or -N(R)C(O)R. In some embodiments, R 22C Each occurrence is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0523] In some embodiments, R 22C is independently at each occurrence an optionally substituted C 1-6 In some embodiments, R 22C In some embodiments, R 22C is independently in each case an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. 22C Each occurrence is independently an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0524] In some embodiments, R 22C is independently at each occurrence an optionally substituted C 1-6 aliphatic, or an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. 22C Each occurrence is independently optionally substituted phenyl, or an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0525] In some embodiments, R 22C is independently at each occurrence an optionally substituted C 1-6 aliphatic or optionally substituted phenyl. In some embodiments, R 22CIn each occurrence is independently an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0526] In some embodiments, R 22C is independently at each occurrence an optionally substituted group selected from phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0527] In some embodiments, R 22C In each case, independently C 1-6 In some embodiments, R 22C In some embodiments, R 22C is independently in each occurrence a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. In some embodiments, R 22C Each occurrence is independently a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0528] In some embodiments, R 22C In each case, independently C 1-6 aliphatic, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. 22C Each occurrence is independently phenyl, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0529] In some embodiments, R 22C In each case, independently C 1-6 In some embodiments, R 22C Each occurrence is independently a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0530] In some embodiments, R 22C Each occurrence is independently phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0531] In some embodiments, R 22C wherein each occurrence is independently oxo, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or optionally substituted C(O) or C(O) 1-6 Aliphatic group.

[0532] In some embodiments, R 22C is independently at each occurrence halogen, -CN, -OH, -O-(optionally substituted C 1-3 aliphatic) or an optionally substituted C 1-3 In some embodiments, R 22C is independently at each occurrence halogen, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 Aliphatic groups are optionally substituted with 1-3 halogens. 22C In some embodiments, R 22C is independently in each instance fluoro or -OH.

[0533] In some embodiments, R 22C is independently at each occurrence oxo, deuterium, halogen, -CN, -OH, -O-(optionally substituted C 1-3 aliphatic) or an optionally substituted C 1-3 In some embodiments, R 22C is independently at each occurrence oxo, deuterium, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 The aliphatic group is optionally substituted with one or more halogen atoms. 22C is independently at each occurrence oxo, deuterium, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C1-3 Aliphatic groups are optionally substituted with 1-3 halogens. 22C In some embodiments, R 22C In some embodiments, R 22C is independently oxo, deuterium, -CN, -CH3, or -CHF2 at each occurrence. In some embodiments, R 22C is independently in each instance deuterium, -CN, -CH3 or -CHF2.

[0534] In some embodiments, R 22C is independently at each occurrence oxo, halogen, -CN, -OH, -O-(optionally substituted C 1-3 aliphatic) or an optionally substituted C 1-3 In some embodiments, R 22C is independently at each occurrence oxo, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 The aliphatic group is optionally substituted with one or more halogen atoms. 22C is independently at each occurrence oxo, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 Aliphatic groups are optionally substituted with 1-3 halogens. 22C In some embodiments, R 22C In some embodiments, R 22C In some embodiments, R 22C is independently in each instance -CN, -CH3 or -CHF2.

[0535] In some embodiments, R 22C is independently in each case selected from the groups depicted in the compounds in Table 1.

[0536] As generally defined above, R T1Cwherein each occurrence is independently oxo, deuterium, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0537] In some embodiments, R T1C wherein each occurrence is independently oxo, halogen, —CN, —NO, —OR, —SR, —NR, —S(O)R, —S(O)NR, —S(O)F, —S(O)R, —S(O)NR, —S(O)(NR)R, —C(O)R, —C(O)OR, —C(O)NR, —C(O)N(R)OR, —OC(O)R, —OC(O)NR, —N(R)C(O)OR, —N(R)C(O)R, —N(R)C(O)NR, —N(R)C(NR)NR, —N(R)S(O)NR, —N(R)S(O)R, —P(O)R, —P(O)(R)OR, —B(OR), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0538] In some embodiments, R T1C-C(O)R, -C(O)OR, -C(O)NR, -C(O)N(R)OR, -OC(O)R, -OC(O)NR, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR). In some embodiments, R T1C is independently in each case an optionally substituted group selected from the group consisting of: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0539] In some embodiments, R T1C In some embodiments, R T1C In some embodiments, R T1C In some embodiments, R T1C In some embodiments, R T1C In some embodiments, R T1C In some embodiments, R T1C In some embodiments, R T1C In some embodiments, R T1C In some embodiments, R T1C In some embodiments, R T1C is -S(O)2F. In some embodiments, R T1C is -S(O)R. In some embodiments, R T1C is -S(O)NR2. In some embodiments, R T1C is -S(O)(NR)R. In some embodiments, R T1C is -C(O)R. In some embodiments, R T1C In some embodiments, R T1C In some embodiments, R T1C is -C(O)N(R)OR. In some embodiments, R T1C is -OC(O)R. In some embodiments, RT1C In some embodiments, R T1C is -N(R)C(O)OR. In some embodiments, R T1C is -N(R)C(O)R. In some embodiments, R T1C is -N(R)C(O)NR2. In some embodiments, R T1C is -N(R)C(NR)NR2. In some embodiments, R T1C is -N(R)S(O)2NR2. In some embodiments, R T1C is -N(R)S(O)2R. In some embodiments, R T1C is -P(O)R2. In some embodiments, R T1C is -P(O)(R)OR. In some embodiments, R T1C It is -B(OR)2.

[0540] In some embodiments, R T1C -C(O)R, -C(O)OR, -C(O)NR, -C(O)N(R)OR, -OC(O)R, -OC(O)NR, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR, -N(R)C(NR)NR, -N(R)S(O)NR, -N(R)S(O)R, -P(O)R, -P(O)(R)OR, or -B(OR).

[0541] In some embodiments, R T1C In some embodiments, R T1C In some embodiments, R T1C In some embodiments, R T1C In some embodiments, R T1C In each case, R is independently -OC(O)R or -OC(O)NR2. T1CIn some embodiments, R T1C Each occurrence is independently -P(O)R2 or -P(O)(R)OR.

[0542] In some embodiments, R T1C In some embodiments, R T1C In some embodiments, R T1C Each occurrence 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.

[0543] In some embodiments, R T1C In each case, R is independently -S(O)2R, -S(O)2NR2, or -S(O)2F. T1C In some embodiments, R T1C Each occurrence is independently -SR, -S(O)2R, or -S(O)R. In some embodiments, R T1C In some embodiments, R T1C In each case, R is independently -S(O)2NR2 or -S(O)NR2. T1C Each occurrence is independently -SR, -S(O)2R, -S(O)2NR2 or -S(O)R.

[0544] In some embodiments, R T1C In some embodiments, R T1C Each occurrence is independently -N(R)S(O)2NR2 or -N(R)S(O)2R. In some embodiments, R T1CEach occurrence is independently -N(R)C(O)OR or -N(R)C(O)R. In some embodiments, R T1C In each case, R is independently -N(R)C(O)NR2 or -N(R)S(O)2NR2. T1C and -N(R)C(O)OR, -N(R)C(O)R, or -N(R)S(O)2R.

[0545] In some embodiments, R T1C In some embodiments, R T1C In some embodiments, R T1C Each occurrence is independently -NR2, -N(R)C(O)OR, -N(R)C(O)R or -N(R)S(O)2R.

[0546] In some embodiments, R T1C is independently at each occurrence an optionally substituted C 1-6 In some embodiments, R T1C In some embodiments, R T1C is independently in each case an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. T1C Each occurrence is independently an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0547] In some embodiments, R T1C is independently at each occurrence an optionally substituted C 1-6 aliphatic, or an optionally substituted 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur. T1C Each occurrence is independently optionally substituted phenyl, or an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur. [0...

Claims

1. A compound of formula I, or a pharmaceutically acceptable salt thereof, wherein: Cy 1 is phenyl; naphthyl; cubanyl; adamantyl; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein Cy 1 By n R 1 replace; Cy 2 is phenyl; naphthyl; cubanyl; adamantyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein Cy 2 By m R 2 replace; Q is for L Q ; T is divided by q R T Substituted divalent C 1-3 Aliphatic chain; Each R 1 Independently -L 1 -R 1A ; Each R 2 Independently -L 2 -R 2A ; Each R T Independently -L T -R TA ;or Two R's T Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is 1 R TTC replace; Two R's 1 Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is 2 R 11C replace; Two R's 2 Together with its intervening atoms, it forms a 3-7 membered saturated, partially unsaturated or aromatic carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is 3 R 22C replace; One R T With an R 1 Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is 4 R T1C replace; or One R T With an R L Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is 5 R TLC replace; L 1 , L 2 , L Q and L T Each independently is a covalent bond or C 1-4 A divalent saturated or unsaturated, linear or branched hydrocarbon chain, wherein one or two methylene units of the chain are optionally and independently replaced by: -CH(R L )-、-C(R L )2-、C 3-6 Cycloalkylene, C 3-6 heterocycloalkylene, -N(R)-, -N(R)C(O)-, -N(R)C(NR)-, -N(R)C(NOR)-, -N(R)C(NCN)-, -C(O)N(R)-, -N(R)S(O)2-, -S(O)2N(R)-, -O-, -C(O)-, -OC(O)-, -C(O)O-, -S-, -S(O)-, or -S(O)2-; Each R 1A Independently 1 R 1C Replaced by R A or R B ; Each R 2A Independently 2 R 2C Replaced by R A or R B ; Each R TA Independently 3 R TC Replaced by R A or R B ; Each R L Independently 4 R LC Replaced by R A or R B ; R A is independently at each occurrence oxo, deuterium, halogen, -CN, -NO2, -OR, -SF5, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)2F, -S(O)R, -S(O)NR2, -S(O)(NR)R, -S(O)(NCN)R, -S(NCN)R, -C(O)R, -C(O)OR, -C(O )NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)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; R B In each case independently C 1-6 aliphatic chain; phenyl; naphthyl; cubanyl; adamantyl; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring; a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; R 1C , R 2C , R TC , R TTC , R 11C , R 22C , R T1C , R TLC and R LC wherein each occurrence is independently oxo, deuterium, halogen, -CN, -NO, -OR, -SF, -SR, -NR, -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), or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; R is independently hydrogen at each occurrence or an optionally substituted group selected from: C 1-6 aliphatic; phenyl; a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or The two R groups on the same nitrogen atom together with their intervening atoms form a 4-7 membered saturated, partially unsaturated or heteroaryl ring having, in addition to nitrogen, 0-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; and n, m, q, p 1 、p 2 、p 3 、p 4 、p 5 、r 1 、r 2 、r 3 and r 4 Each independently is 0, 1, 2, 3, 4 or 5.

2. The compound according to claim 1, wherein Cy 1 yes 3. The compound according to claim 1 or 2, wherein the compound is a compound of formula II: or a pharmaceutically acceptable salt thereof.

4. A compound according to any one of the preceding claims, wherein Q is -C(O)N(R)-, -C(O)N(R)CH2-, -N(R)-, -CH2C(O)N(R)-, -N(R)C(O)N(R)- or a covalent bond.

5. A compound according to any one of the preceding claims, wherein T is in represents the bond to Q, and Indicates connection to Cy 1 key.

6. A compound according to any one of the preceding claims, wherein the compound is a compound of formula V, VI, VII, VIII, IX or X: or a pharmaceutically acceptable salt thereof.

7. A compound according to any one of the preceding claims, wherein both R T Together with its intervening atoms, it forms a 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is 1 R TTC replace.

8. A compound according to any one of claims 1 to 5, wherein T is in represents the bond to Q, and Indicates connection to Cy 1 key.

9. The compound according to any one of claims 1 to 6 and claim 8, wherein the compound is a compound of formula XI, XII, XIII, XIV, XV, XVI, XVII, XVIII or XIX: or a pharmaceutically acceptable salt thereof.

10. The compound according to any one of claims 1 to 3, wherein the compound is a compound of formula XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, XXXIII, XXXIV, XXXV or XXXVI: or a pharmaceutically acceptable salt thereof.

11. A compound according to any one of the preceding claims, wherein Cy 2 yes 12. The compound according to any one of claims 1 to 10, wherein Cy 2 yes 13. The compound according to any one of claims 1 to 6, wherein the compound is a compound of formula XX, XXI, XXII, XXIII, XXIV or XXV: or a pharmaceutically acceptable salt thereof.

14. The compound according to any one of claims 1 to 6 and 10 to 13, wherein R T is a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 5-12 membered saturated or partially unsaturated bicyclic carbocyclic ring; each of which is 3 R TC replace.

15. A compound according to any one of the preceding claims, wherein L 1 It is a covalent bond.

16. A compound according to any one of the preceding claims, wherein each R 1 are independently halogen, -CN, -O-(C 1-6 Aliphatic chain) or C substituted by 0-5 halogens 1-6 Aliphatic chain.

17. A compound according to any one of the preceding claims, wherein at least one R 1 It's a halogen.

18. A compound according to any one of the preceding claims, wherein at least two R 1 It's a halogen.

19. A compound according to any one of the preceding claims, wherein at least three R 1 It's a halogen.

20. A compound according to any one of the preceding claims, wherein at least one R 1 is C optionally substituted by 1 to 3 halogens 1-3 Aliphatic group.

21. A compound according to any one of the preceding claims, wherein at least one R 1 is -OC optionally substituted by 1 to 3 halogens 1-3 Aliphatic group.

22. A compound according to any one of the preceding claims, wherein n is 1, 2, 3, 4 or 5.

23. A compound according to any one of the preceding claims, wherein R 2 Yes-N(R)-R 2A 、-N(R)C(O)-R 2A 、-CH(R L )N(R)-R 2A 、-N(R)C(O)CH(R L )-R 2A 、-CH(R L )OR 2A 、-CH(R L )-R 2A or -R 2A .

24. A compound according to any one of the preceding claims, wherein R 2 Yes-N(H)-R 2A 、-N(H)C(O)-R 2A or -CH2-R 2A .

25. A compound according to any one of the preceding claims, wherein R 2A is r 2 R 2C Replaced by R B .

26. A compound according to any one of the preceding claims, wherein R 2A is phenyl; naphthyl; an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R 2A By r 2 R 2C replace.

27. A compound according to any one of the preceding claims, wherein R 2A is r 2 R 2C Substituted phenyl.

28. A compound according to any one of claims 1 to 25, wherein R 2A is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is r 2 R 2C replace.

29. The compound according to any one of claims 1 to 25, wherein R 2A is a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the ring is surrounded by r2 R 2C replace.

30. The compound according to any one of claims 1 to 25, wherein R 2 yes 31. A compound according to any one of claims 1 to 25, wherein R 2 yes 32. A compound according to any one of claims 1 to 25, wherein R 2 yes 33. A compound according to any one of the preceding claims, wherein m is 1.

34. The compound according to any one of claims 1 to 33, wherein R 2C is independently in each case C optionally substituted by 1-6 Aliphatic group: (i) 1 or 2 independently selected from -O-(C 1-6 Aliphatic), -OH, -N(C 1-6 aliphatic) 2 and -CN; and (ii) 1, 2 or 3 atoms independently selected from halogen and deuterium.

35. The compound according to any one of claims 1 to 33, wherein R 2C is independently at each occurrence oxo, deuterium, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 Aliphatic groups are optionally substituted with one or more halogen atoms.

36. The compound according to any one of claims 1 to 35, wherein R TC is independently at each occurrence oxo, deuterium, halogen, -CN, -OH, -O-(C 1-3 Aliphatic) or C 1-3 An aliphatic group, in which each C 1-3 Aliphatic groups are optionally substituted with one or more halogen atoms.

37. A compound selected from those shown in Table 1 or a pharmaceutically acceptable salt thereof.

38. A pharmaceutical composition comprising a compound according to any one of the preceding claims and a pharmaceutically acceptable carrier.

39. A method of inhibiting PI3Kα signaling activity in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to any one of claims 1 to 37 or a pharmaceutical composition according to claim 38.

40. A method of treating a PI3Kα-mediated disorder in a subject, comprising administering to the subject in need thereof a therapeutically effective amount of a compound according to any one of claims 1 to 37 or a pharmaceutical composition according to claim 38.

41. A method of treating a cell proliferative disease in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to any one of claims 1 to 37 or a pharmaceutical composition according to claim 38.

42. The method of claim 41, wherein the cell proliferative disorder is cancer.

43. The method of claim 42, wherein the cancer is breast cancer.

44. The method of claim 42, wherein the cancer is ovarian cancer.

45. The method of claim 44, wherein the ovarian cancer is clear cell ovarian cancer.

46. ​​The method of any one of claims 39 to 45, wherein the subject has a P13Kα containing at least one of the following mutations: H1047R, E542K, and E545K.

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