Compounds for inhibiting or degrading target proteins, compositions containing same, methods for making same, and methods for using same

Abstract

Provided herein are heterobifunctional compounds that find use as modulators of targeted ubiquitination. Also provided herein are pharma- ceutically acceptable compositions comprising the compounds and methods of using the compounds and compositions in the treatment of various diseases, conditions, or disorders.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 304,497, filed January 28, 2022, and U.S. Provisional Patent Application No. 63 / 183,619, filed May 3, 2021, the entire contents of which are incorporated herein by reference.

[0002] Technical Field FIELD OF THE DISCLOSURE

[0002] The present disclosure provides heterobifunctional compounds for proteolyzing target proteins and methods for treating diseases regulated by the target proteins. [Background technology]

[0003]

[0003] Degradation of cellular proteins is required for the normal maintenance of cellular functions, including proliferation, differentiation, and cell death. The irreversible nature of proteolysis makes it well suited to act as a regulatory switch to control unidirectional processes. This principle is evident in the control of the cell cycle, where the initiation of DNA replication, chromosome segregation, and exit from mitosis are triggered by the destruction of key regulatory proteins.

[0004]

[0004] In eukaryotes, protein degradation is primarily mediated through the ubiquitin pathway, in which proteins targeted for destruction are ligated to the polypeptide ubiquitin. The process of protein ubiquitination proceeds through an enzyme cascade consisting of ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and E3 ubiquitin ligases (E3). E3 ligases are diverse proteins that selectively modify proteins by covalently attaching ubiquitin to lysine, serine, threonine, or cysteine ​​residues within the substrate of each specific E3.

[0005] Modulation of E3 ligases as therapeutic agents may be more attractive than general proteasome inhibitors due to their specificity for specific protein substrates. Specific degradation of target proteins can be achieved using heterobifunctional small molecules that recruit target proteins to ubiquitin ligases, thereby promoting ubiquitination and proteasomal degradation of the target protein. Summary of the Invention [Means for solving the problem]

[0006]

[0006] Provided herein are heterobifunctional compounds of formula (I), compositions comprising the compounds, methods of making the compounds, and methods of using the compounds and compositions in the treatment of diseases or disorders mediated by target proteins. In certain embodiments, the compounds degrade the target protein via the ubiquitin proteolytic pathway.

[0007] In one aspect, provided herein are compounds of formula (I), or stereoisomers and / or pharmaceutically acceptable salts thereof: [ka] The left side of the molecule is a ubiquitin ligase harness. The right side of the molecule (the Y portion) is capable of binding to a target protein. The middle portion of the molecule (the L portion) is a linker. W is -CH or -N. Z is [ka] The compounds are described in detail herein.

[0008] In one aspect, provided herein are compounds of formula (I), or stereoisomers and / or pharmaceutically acceptable salts thereof: [ka] The left side of the molecule is a ubiquitin ligase harness. The right side of the molecule (the Y portion) is capable of binding to a target protein. The middle portion of the molecule (the L portion) is a linker. W is -CH or -N. Z is [ka] The compounds are described in detail herein.

[0009]

[0009] In another aspect, provided herein is a composition comprising a compound of Formula (I). In certain embodiments, the composition is a pharmaceutical composition. The pharmaceutical composition comprises the compound and any suitable pharmaceutically acceptable carrier, excipient, or diluent.

[0010] In another aspect, provided herein is a method for making a degradation compound. The method comprises linking a target-binding moiety, Y, that binds to a target protein to a degron, either directly or via a linker, L, to form a degradation compound. In certain embodiments, the target-binding moiety, Y, is a moiety described herein. In certain embodiments, the degron is a harness described herein. In certain embodiments, the linker, L, is a linker described herein. The degron can be linked to L and then to Y, or Y can be linked to L and then to the degron. In certain embodiments, the method further comprises contacting the target protein with the degradation compound.

[0011] In another aspect, provided herein are methods of using the compounds or compositions described herein. In certain embodiments, the method is for treating a disease or disorder mediated by a target protein in a patient in need thereof. In certain embodiments, the target protein is Bruton's tyrosine kinase (BTK). In certain embodiments, the target protein is tyrosine-protein kinase (ITK / TSK). In certain embodiments, the target protein is bromodomain-containing protein 4 (BRD4). In certain embodiments, the target protein is FMS-like tyrosine kinase 3 (FLT-3). In certain embodiments, the target protein is Brg / Brahma-associated factor (BAF complex). In certain embodiments, the target protein is inducible myeloid leukemia cell differentiation protein (MCL-1). In certain embodiments, the target protein is signal transducer and activator of transcription 3 (STAT3). In certain embodiments, the target protein is barrier to autointegration factor (BAF). In certain embodiments, the target protein is BCR-ABL. In certain embodiments, the disease is cancer. In certain embodiments, the disease is an autoimmune disease. In certain embodiments, the target protein is selected from the group consisting of CDK4, CDK6, SHP-2, FGFR1, FGFR3, FGFR1 fusion, FGFR3 fusion, MDM2, TRIM24, SARS-COV2 proteins (e.g., Mpro or nsp5), PI3K, PI3K delta, MEK, BCR-ABL, MLL, MALT1, IRAK1, IRAK4, and kinases (e.g., broad-spectrum). In certain embodiments, the disease is an autoimmune disease. In certain embodiments, the target protein is selected from the group consisting of CDK4, CDK6, SHP-2, FGFR1, FGFR3, FGFR1 fusion, FGFR3 fusion, MDM2, TRIM24, SARS-COV2 proteins (e.g., Mpro or nsp5), PI3K, PI3K delta, MEK, BCR-ABL, MLL, and MALT1. In certain embodiments, the target protein is SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2).In certain embodiments, the target protein is a fibroblast growth factor receptor (FGFR). In certain embodiments, the target protein is an FGFR1 fusion. In certain embodiments, the target protein is an FGFR3 fusion. In certain embodiments, the target protein is a mouse double minute 2 homolog (MDM2). In certain embodiments, the target protein is a tripartite motif-containing 24 (TRIM24). In certain embodiments, the target protein is SARS-COV2 main protease (Mpro). In certain embodiments, the target protein is phosphoinositide 3-kinase (PI3K) delta. In certain embodiments, the target protein is a mitogen-activated protein kinase kinase (MEK). In certain embodiments, the target protein is histone-lysine N-methyltransferase 2A (MLL). In certain embodiments, the target protein is mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1). In certain embodiments, the target protein is interleukin-1 receptor-associated kinase 1 (IRAK1). In certain embodiments, the target protein is one or more kinases. In certain embodiments, the target protein is multiple kinases.

[0012]

[0012] In one aspect, provided herein are methods for treating or preventing cancer in a subject in need thereof. In certain embodiments, the method comprises orally administering to the subject an amount of a heterobifunctional compound capable of inducing proteolysis of a target protein, wherein the target protein is selected from the group consisting of BTK; ITK / TSK; BRD4; FLT-3; BAF; BAF complex; MCL-1; STAT3; and BCR-ABL. In certain embodiments, the method comprises orally administering to the subject an amount of a heterobifunctional compound capable of inducing proteolysis of a target protein, wherein the target protein is selected from the group consisting of CDK4, CDK6, SHP-2, FGFR1, FGFR3, FGFR1 fusion, FGFR3 fusion, MDM2, TRIM24, a SARS-COV2 protein (e.g., Mpro or nsp5), PI3K, PI3K delta, MEK, BCR-ABL, MLL, and MALT1. In certain embodiments, the method comprises orally administering to a subject an amount of a heterobifunctional compound capable of inducing proteolysis of a target protein, wherein the target protein is selected from the group consisting of CDK4, CDK6, SHP-2, FGFR1, FGFR3, FGFR1 fusion, FGFR3 fusion, MDM2, TRIM24, a SARS-COV2 protein (e.g., Mpro, or nsp5), PI3K, PI3K delta, MEK, BCR-ABL, MLL, MALT1, IRAK1, and a kinase (e.g., broad spectrum). In certain embodiments, the amount is effective to treat or prevent cancer.

[0013]

[0013] Also provided herein are uses of the compounds described herein, and compositions thereof, for the treatment of cancer. Also provided herein are uses of the compounds described herein, and compositions thereof, for the treatment of autoimmune and inflammatory diseases. [Brief explanation of the drawings]

[0014] [Figure 1]

[0014] Figure 1 shows in vitro degradation of ITK in the HiBiT cell line. [Figure 2A]

[0015] 1 shows the in vivo degradation of ITK in mouse splenocytes after administration of compounds 30 and 31 provided herein as observed by Western blotting. [Figure 2B]

[0015] Figure 1 shows a graph of ITK levels in mouse splenocytes after administration of compounds 30 and 32 provided herein. [Figure 3A]

[0016] 1 shows the in vivo degradation of ITK in mouse splenocytes after administration of compounds 30 and 29 provided herein as observed by Western blotting. [Figure 3B]

[0016] Figure 1 shows a graph of ITK levels in mouse splenocytes after administration of compounds 30 and 29 provided herein. [Figure 3C]

[0016] Figure 1 shows the concentration of compound 30 over time in vivo. DETAILED DESCRIPTION OF THE INVENTION

[0015] Detailed Description of the Preferred Embodiments

[0017] Provided herein are heterobifunctional compounds that induce proteolysis of a target protein via the ubiquitin proteolytic pathway. Also provided herein are compounds of formula (I-XXIX), (Ia-If), (IIa-IIw), or (I1-I115), and stereoisomers and / or pharmaceutically acceptable salts thereof.

[0016]

[0018] As used herein, the following definitions shall apply unless otherwise indicated.

[0017] definition

[0019] As used herein, the term "hydroxyl" or "hydroxy" refers to an --OH moiety.

[0018]

[0020] As used herein, the term "aliphatic" encompasses the terms alkyl, alkenyl, and alkynyl, each of which is optionally substituted as described below.

[0019]

[0021] As used herein, an "alkyl" group refers to a saturated aliphatic hydrocarbon group containing 1 to 12 (e.g., 1 to 8, 1 to 6, or 1 to 4) carbon atoms. The alkyl group can be straight-chained or branched. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-heptyl, or 2-ethylhexyl. Alkyl groups include halo, phospho, alicyclic (e.g., cycloalkyl or cycloalkenyl), heteroalicyclic (e.g., heterocycloalkyl or heterocycloalkenyl), aryl, heteroaryl, alkoxy, aroyl, heteroaroyl, acyl (e.g., (aliphatic)carbonyl, (alicyclic)carbonyl, or (heteroalicyclic)carbonyl), nitro, cyano, amido (e.g., (cycloalkylalkyl)carbonylamino, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkylalkyl)carbonylamino, heteroarylcarbonylamino, heteroaralkylcarbonylamino, alkylaminocarbonyl, and the like). and optionally substituted with one or more substituents such as aryl, cycloalkylaminocarbonyl, heterocycloalkylaminocarbonyl, arylaminocarbonyl, or heteroarylaminocarbonyl), amino (e.g., aliphatic amino, cycloaliphatic amino, or heteroalicyclic amino), sulfonyl (e.g., aliphatic -SO2-), sulfinyl, sulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamido, oxo, carboxy, carbamoyl, cycloaliphatic oxy, heterocycloaliphatic oxy, aryloxy, heteroaryloxy, aralkyloxy, heteroarylalkoxy, alkoxycarbonyl, alkylcarbonyloxy, or hydroxy.Some examples of substituted alkyl include, but are not limited to, carboxyalkyl (such as HOOC-alkyl, alkoxycarbonylalkyl, and alkylcarbonyloxyalkyl), cyanoalkyl, hydroxyalkyl, alkoxyalkyl, acylalkyl, aralkyl, (alkoxyaryl)alkyl, (sulfonylamino)alkyl (such as (alkyl-SO2-amino)alkyl), aminoalkyl, amidoalkyl, (alicyclic)alkyl, or haloalkyl.

[0020]

[0022] As used herein, an "alkenyl" group refers to an aliphatic carbon group containing 2 to 8 (e.g., 2 to 4 or 2 to 6) carbon atoms and at least one double bond. Like an alkyl group, an alkenyl group can be straight-chained or branched. Examples of alkenyl groups include, but are not limited to, allyl, 1- or 2-isopropenyl, 2-butenyl, and 2-hexenyl. Alkenyl groups include halo, phospho, alicyclic (e.g., cycloalkyl or cycloalkenyl), heteroalicyclic (e.g., heterocycloalkyl or heterocycloalkenyl), aryl, heteroaryl, alkoxy, aroyl, heteroaroyl, acyl (e.g., (aliphatic)carbonyl, (alicyclic)carbonyl, or (heteroalicyclic)carbonyl), nitro, cyano, amido (e.g., (cycloalkylalkyl)carbonylamino, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkylalkyl)carbonylamino, heteroarylcarbonylamino, heteroaralkylcarbonylamino, alkylaminocarbonyl, cycloalkenyl, The alkyl group may be optionally substituted with one or more substituents such as alkylaminocarbonyl, heterocycloalkylaminocarbonyl, arylaminocarbonyl, or heteroarylaminocarbonyl), amino (e.g., aliphatic amino, alicyclic amino, heteroalicyclic amino, or aliphatic sulfonylamino), sulfonyl (e.g., alkyl-SO2-, alicyclic-SO2-, or aryl-SO2-), sulfinyl, sulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamido, oxo, carboxy, carbamoyl, alicyclicoxy, heteroalicyclicoxy, aryloxy, heteroaryloxy, aralkyloxy, heteroaralkoxy, alkoxycarbonyl, alkylcarbonyloxy, or hydroxy.Some examples of substituted alkenyls include, but are not limited to, cyanoalkenyl, alkoxyalkenyl, acylalkenyl, hydroxyalkenyl, aralkenyl, (alkoxyaryl)alkenyl, (sulfonylamino)alkenyl (such as (alkyl-SO2-amino)alkenyl), aminoalkenyl, amidoalkenyl, (alicyclic)alkenyl, or haloalkenyl.

[0021]

[0023] As used herein, an "alkynyl" group refers to an aliphatic carbon group containing 2 to 8 (e.g., 2 to 4 or 2 to 6) carbon atoms and having at least one triple bond. Alkynyl groups can be straight-chained or branched. Examples of alkynyl groups include, but are not limited to, propargyl and butynyl. Alkynyl groups include aroyl, heteroaroyl, alkoxy, cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy, nitro, carboxy, cyano, halo, hydroxy, sulfo, mercapto, sulfanyl (e.g., aliphatic sulfanyl or alicyclic sulfanyl), sulfinyl (e.g., aliphatic sulfinyl or alicyclic sulfinyl), sulfonyl (e.g., aliphatic -SO2-, aliphatic amino-SO2-, or alicyclic -SO2-), amido (e.g., aminocarbonyl, alkylaminocarbonyl, alkylcarbonylamino, cycloalkylaminocarbonyl, heterocycloalkylaminocarbonyl, cycloalkylcarbonylamino, arylaminocarbonyl,

[0047] The cycloaliphatic amino group may be optionally substituted with one or more substituents such as cycloaliphatic, ...

[0022]

[0024] As used herein, "amide" encompasses both "aminocarbonyl" and "carbonylamino." These terms, when used alone or with another group, include -N(R X )-C(O)-R Y or -C(O)-N(RX )2, and -C(O)-N(R when used internally X )- or -N(R X )-C(O)-, where R X and R Y can be aliphatic, alicyclic, aryl, araliphatic, heteroalicyclic, heteroaryl, or heteroaraliphatic. Examples of amide groups include alkylamido (such as alkylcarbonylamino or alkylaminocarbonyl), (heteroalicyclic)amide, (heteroaralkyl)amide, (heteroaryl)amide, (heterocycloalkyl)alkylamide, arylamide, aralkylamide, (cycloalkyl)alkylamide, or cycloalkylamide.

[0023]

[0025] As used herein, an "amino" group is -NR X R Y where R X and R Y is independently hydrogen (H or -H), aliphatic, alicyclic, (alicyclic)aliphatic, aryl, araliphatic, heteroalicyclic, (heteroalicyclic)aliphatic, heteroaryl, carboxy, sulfanyl, sulfinyl, sulfonyl, (aliphatic)carbonyl, (alicyclic)carbonyl, ((alicyclic)aliphatic)carbonyl, arylcarbonyl, (araliphatic)carbonyl, (heteroalicyclic)carbonyl, ((heteroalicyclic)aliphatic)carbonyl, (heteroaryl)carbonyl, or (heteroaraliphatic)carbonyl, each of which is defined herein and optionally substituted. Examples of amino groups include alkylamino, dialkylamino, or arylamino. When the term "amino" is not a terminal group (e.g., alkylcarbonylamino), it is not an -NR X - where R X has the same meaning as defined above.

[0024]

[0026] As used herein, an "aryl" group, used alone or as part of a larger moiety, such as "aralkyl," "aralkoxy," or "aryloxyalkyl," refers to monocyclic (e.g., phenyl); bicyclic (e.g., indenyl, naphthalenyl, tetrahydronaphthyl, or tetrahydroindenyl); and tricyclic (e.g., fluorenyltetrahydrofluorenyl, tetrahydroanthracenyl, or anthracenyl) ring systems, where the monocyclic ring system is aromatic or at least one of the rings of the bicyclic or tricyclic ring system is aromatic. Bicyclic and tricyclic groups include benzo-fused 2- to 3-membered carbocyclic rings. For example, benzo-fused groups include groups having two or more C 4~8 Included are phenyls fused to carbocyclic moieties. Aryl includes aliphatic (e.g., alkyl, alkenyl, or alkynyl); alicyclic; (alicyclic)aliphatic; heteroalicyclic; (heteroalicyclic)aliphatic; aryl; heteroaryl; alkoxy; (alicyclic)oxy; (heteroalicyclic)oxy; aryloxy; heteroaryloxy; (araliphatic)oxy; (heteroaraliphatic)oxy; aroyl; heteroaroyl; amino; oxo (on the non-aromatic carbocyclic ring of a benzo-fused bicyclic or tricyclic aryl); nitro; carboxy; amido; acyl (e.g., (aliphatic)carbonyl; (alicyclic)carbonyl). Aryl is optionally substituted with one or more substituents including: ((alicyclic)aliphatic)carbonyl; (araliphatic)carbonyl; (heteroalicyclic)carbonyl; ((heteroalicyclic)aliphatic)carbonyl; or (heteroaraliphatic)carbonyl); sulfonyl (e.g., aliphatic -SO2- or amino-SO2-); sulfinyl (e.g., aliphatic -S(O)- or alicyclic -S(O)-); sulfanyl (e.g., aliphatic -S-); cyano; halo; hydroxy; mercapto; sulfoxy; urea; thiourea; sulfamoyl; sulfamido; or carbamoyl. Alternatively, aryl can be unsubstituted.

[0025]

[0027] Non-limiting examples of substituted aryls include haloaryls (e.g., mono-, di-(p,m-dihaloaryls, etc.), and (trihalo)aryls); (carboxy)aryls (e.g., (alkoxycarbonyl)aryls, ((aralkyl)carbonyloxy)aryls, and (alkoxycarbonyl)aryls); (amido)aryls (e.g., (aminocarbonyl)aryls, (((alkylamino)alkyl)aminocarbonyl)aryls, (alkylcarbonyl)aminoaryls, (arylaminocarbonyl)aryls, and (((heteroaryl)amino)carbonyl)aryls); aminoaryls (e.g., ((alkylsulfonyl)amino)aryls or ((dialkyl)amino)aryls); (cyanoalkyl)aryls; (alkoxy)aryls; (sulfamoyl)aryls (e.g., (amino) (aminosulfonyl)aryl; (alkylsulfonyl)aryl; (cyano)aryl; (hydroxyalkyl)aryl; ((alkoxy)alkyl)aryl; (hydroxy)aryl, ((carboxy)alkyl)aryl; (((dialkyl)amino)alkyl)aryl; (nitroalkyl)aryl; (((alkylsulfonyl)amino)alkyl)aryl; ((heteroalicyclic)carbonyl)aryl; ((alkylsulfonyl)alkyl)aryl; (cyanoalkyl)aryl; (hydroxyalkyl)aryl; (alkylcarbonyl)aryl; alkylaryl; (trihaloalkyl)aryl; p-amino-m-alkoxycarbonylaryl; p-amino-m-cyanoaryl; p-halo-m-aminoaryl; or (m-(heteroalicyclic)-o-(alkyl))aryl.

[0026]

[0028] As used herein, "araliphatic," such as an "aralkyl" group, refers to an aliphatic group substituted with an aryl group (e.g., C 1~4 "Aliphatic", "alkyl", and "aryl" are defined herein. An example of an araliphatic, such as an aralkyl, group is benzyl.

[0027]

[0029] As used herein, an "aralkyl" group refers to an alkyl group substituted with an aryl group (e.g., C 1~4 "Alkyl" and "aryl" are both defined above. An example of an aralkyl group is benzyl. Aralkyl refers to an aliphatic (e.g., alkyl, alkenyl, or alkynyl, including carboxyalkyl, hydroxyalkyl, or haloalkyl, including trifluoromethyl), alicyclic (e.g., cycloalkyl or cycloalkenyl), (cycloalkyl)alkyl, heterocycloalkyl, (heterocycloalkyl)alkyl, aryl, heteroaryl, alkoxy, cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy, heteroaralkyloxy, aroyl, heteroaroyl, nitro, carboxy, alkoxycarbonyl, alkylcarbonyl and optionally substituted with one or more substituents such as aryloxy, amido (e.g., aminocarbonyl, alkylcarbonylamino, cycloalkylcarbonylamino, (cycloalkylalkyl)carbonylamino, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkylalkyl)carbonylamino, heteroarylcarbonylamino, or heteroaralkylcarbonylamino), cyano, halo, hydroxy, acyl, mercapto, alkylsulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamido, oxo, or carbamoyl.

[0028]

[0030] As used herein, "bicyclic ring system" includes 6- to 12-membered (e.g., 8- to 12-membered or 9-, 10-, or 11-membered) structures forming two rings, where the two rings have at least one atom in common (e.g., two atoms in common). Bicyclic ring systems include bicycloaliphatic (e.g., bicycloalkyl or bicycloalkenyl), bicycloheteroaliphatic, bicyclic aryl, and bicyclic heteroaryl.

[0029]

[0031] As used herein, an "alicyclic" group encompasses a "cycloalkyl" group and a "cycloalkenyl" group, each of which is optionally substituted as described below.

[0030]

[0032] As used herein, a "cycloalkyl" group refers to a saturated carbocyclic monocyclic or bicyclic (fused or bridged) ring of 3 to 10 (e.g., 5 to 10) carbon atoms. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, norbornyl, cubyl, octahydro-indenyl, decahydro-naphthyl, bicyclo[3.2.1]octyl, bicyclo[2.2.2]octyl, bicyclo[3.3.1]nonyl, bicyclo[3.3.2]decyl, bicyclo[2.2.2]octyl, adamantyl, or ((aminocarbonyl)cycloalkyl)cycloalkyl.

[0031]

[0033] As used herein, a "cycloalkenyl" group refers to a non-aromatic carbocyclic ring of 3 to 10 (e.g., 4 to 8) carbon atoms having one or more double bonds. Examples of cycloalkenyl groups include cyclopentenyl, 1,4-cyclohexa-dienyl, cycloheptenyl, cyclooctenyl, hexahydro-indenyl, octahydro-naphthyl, cyclohexenyl, bicyclo[2.2.2]octenyl, or bicyclo[3.3.1]nonenyl.

[0032]

[0034] A cycloalkyl or cycloalkenyl group can be phospho, aliphatic (e.g., alkyl, alkenyl, or alkynyl), alicyclic, (alicyclic)aliphatic, heteroalicyclic, (heteroalicyclic)aliphatic, aryl, heteroaryl, alkoxy, (alicyclic)oxy, (heteroalicyclic)oxy, aryloxy, heteroaryloxy, (araliphatic)oxy, (heteroaraliphatic)oxy, aroyl, heteroaroyl, amino, amido (e.g., (aliphatic)carbonylamino, (alicyclic)carbonylamino, ((alicyclic)aliphatic)carbonylamino, (aryl)carbonylamino, (araliphatic)carbonylamino, (heteroalicyclic)carbonylamino, ((heteroalicyclic)aliphatic)carbonylamino, (heteroaryl)carbonylamino, or or (heteroaraliphatic)carbonylamino), nitro, carboxy (e.g., HOOC-, alkoxycarbonyl, or alkylcarbonyloxy), acyl (e.g., (alicyclic)carbonyl, ((alicyclic)aliphatic)carbonyl, (araliphatic)carbonyl, (heteroalicyclic)carbonyl, ((heteroalicyclic)aliphatic)carbonyl, or (heteroaraliphatic)carbonyl), cyano, halo, hydroxy, mercapto, sulfonyl (e.g., alkyl-SO- and aryl-SO-), sulfinyl (e.g., alkyl-S(O)-), sulfanyl (e.g., alkyl-S-), sulfoxy, urea, thiourea, sulfamoyl, sulfamido, oxo, or carbamoyl.

[0033]

[0035] As used herein, the term "heteroalicyclic" encompasses heterocycloalkyl and heterocycloalkenyl groups, each of which is optionally substituted as described below.

[0034]

[0036] As used herein, a "heterocycloalkyl" group refers to a 3- to 10-membered monocyclic or bicyclic (fused, bridged, or spiro) (e.g., 5- to 10-membered monocyclic or bicyclic) saturated ring structure in which one or more of the ring atoms is a heteroatom (e.g., nitrogen (N), oxygen (O), sulfur (S), or a combination thereof). Non-limiting examples of heterocycloalkyl groups include piperidyl, piperazyl, tetrahydropyranyl, tetrahydrofuryl, 1,4-dioxolanyl, 1,4-dithianyl, 1,3-dioxolanyl, oxazolidyl, isoxazolidyl, morpholinyl, thiomorpholinyl, octahydrobenzofuryl, octahydrochromenyl, octahydrothiochromenyl, octahydroindolyl, octahydropyrindinyl, decahydroquinolinyl, o- ... octahydrobenzo[b]thiopheneyl, 2-oxa-bicyclo[2.2.2]octyl, 1-aza-bicyclo[2.2.2]octyl, 3-aza-bicyclo[3.2.1]octyl, decahydro-2,7-naphthyridine, 2,8-diazaspiro[4.5]decane, 2,7-diazaspiro[3.5]nonane, octahydropyrrolo[3,4-c]pyrrole, octahydro-1H-pyrrolo[3,4-b]pyridine, and 2,6-dioxa-tricyclo[3.3.1.0]octyl. 3,7 Monocyclic heterocycloalkyl groups can be fused with a phenyl moiety to form structures such as tetrahydroisoquinoline, which can be classified as heteroaryls.

[0035]

[0037] As used herein, a "heterocycloalkenyl" group refers to a monocyclic or bicyclic (e.g., 5- to 10-membered monocyclic or bicyclic) non-aromatic ring structure having one or more double bonds, in which one or more of the ring atoms is a heteroatom (e.g., N, O, or S). Monocyclic and bicyclic heteroalicyclic rings are numbered according to standard chemical nomenclature.

[0036]

[0038] A heterocycloalkyl or heterocycloalkenyl group can be phospho, aliphatic (e.g., alkyl, alkenyl, or alkynyl), alicyclic, (alicyclic)aliphatic, heteroalicyclic, (heteroalicyclic)aliphatic, aryl, heteroaryl, alkoxy, (alicyclic)oxy, (heteroalicyclic)oxy, aryloxy, heteroaryloxy, (araliphatic)oxy, (heteroaraliphatic)oxy, aroyl, heteroaroyl, amino, amido (e.g., (aliphatic)carbonylamino, (alicyclic)carbonylamino, ((alicyclic)aliphatic)carbonylamino, (aryl)carbonylamino, (araliphatic)carbonylamino, (heteroalicyclic)carbonylamino, ((heteroalicyclic)aliphatic)carbonylamino, (heteroaryl)carbonylamino, or or (heteroaraliphatic)carbonylamino), nitro, carboxy (e.g., HOOC-, alkoxycarbonyl, or alkylcarbonyloxy), acyl (e.g., (alicyclic)carbonyl, ((alicyclic)aliphatic)carbonyl, (araliphatic)carbonyl, (heteroalicyclic)carbonyl, ((heteroalicyclic)aliphatic)carbonyl, or (heteroaraliphatic)carbonyl), nitro, cyano, halo, hydroxy, mercapto, sulfonyl (e.g., alkylsulfonyl or arylsulfonyl), sulfinyl (e.g., alkylsulfinyl), sulfanyl (e.g., alkylsulfanyl), sulfoxy, urea, thiourea, sulfamoyl, sulfamido, oxo, or carbamoyl.

[0037]

[0039] As used herein, a "heteroaryl" group refers to a monocyclic, bicyclic, or tricyclic ring system having 4 to 15 ring atoms, one or more of which is a heteroatom (e.g., N, O, S, or a combination thereof), and in which the monocyclic ring system is aromatic or in which at least one of the rings of a bicyclic or tricyclic ring system is aromatic. Heteroaryl groups include benzo-fused ring systems having two to three rings. For example, benzo-fused groups include benzo (e.g., indolyl, indolyl, isoindolyl, 3H-indolyl, indolinyl, benzo[b]furyl, benzo[b]thiophen-yl, quinolinyl, or isoquinolinyl) fused with one or two 4- to 8-membered heteroalicyclic moieties. Some examples of heteroaryl are azetidinyl, pyridyl, 1H-indazolyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, tetrazolyl, benzofuryl, isoquinolinyl, benzthiazolyl, xanthene, thioxanthene, phenothiazine, dihydroindole, benzo[1,3]dioxole, benzo[b]furyl, benzo[b]thiophenyl, indazolyl, benzimidazolyl, benzthiazolyl, puryl, cinnolyl, quinolyl, quinazolyl, phthalazyl, quinazolyl, quinoxalyl, isoquinolyl, 4H-quinolidyl, benzo-1,2,5-thiadiazolyl, or 1,8-naphthyridyl. Other examples of heteroaryls include 1,2,3,4-tetrahydroisoquinoline and 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine.

[0038]

[0040] Monocyclic heteroaryls include, but are not limited to, furyl, thiophen-yl, 2H-pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, 1,3,4-thiadiazolyl, 2H-pyranyl, 4H-pyranyl, pyridyl, pyridazyl, pyrimidyl, pyrazolyl, pyrazyl, or 1,3,5-triazyl. Monocyclic heteroaryls are numbered according to standard chemical nomenclature.

[0039]

[0041] Bicyclic heteroaryls include, but are not limited to, indolyl, indolyl, isoindolyl, 3H-indolyl, indolinyl, benzo[b]furyl, benzo[b]thiophenyl, quinolinyl, isoquinolinyl, indazolyl, benzimidazyl, benzthiazolyl, purinyl, 4H-quinolizyl, quinolyl, isoquinolyl, cinnolyl, phthalazyl, quinazolyl, quinoxalyl, 1,8-naphthyridyl, or pteridyl. Bicyclic heteroaryls are numbered according to standard chemical nomenclature.

[0040]

[0042] Heteroaryl includes aliphatic (e.g., alkyl, alkenyl, or alkynyl); alicyclic; (alicyclic)aliphatic; heteroalicyclic; (heteroalicyclic)aliphatic; aryl; heteroaryl; alkoxy; (alicyclic)oxy; (heteroalicyclic)oxy; aryloxy; heteroaryloxy; (araliphatic)oxy; (heteroaraliphatic)oxy; aroyl; heteroaroyl; amino; oxo (on a non-aromatic carbocyclic or heterocyclic ring of a bicyclic or tricyclic heteroaryl); carboxy; amido; acyl (e.g., aliphatic carbonyl; (alicyclic)carbonyl). Heteroaryl is optionally substituted with one or more substituents such as carbonyl; ((alicyclic)aliphatic)carbonyl; (araliphatic)carbonyl; (heteroalicyclic)carbonyl; ((heteroalicyclic)aliphatic)carbonyl; or (heteroaraliphatic)carbonyl; sulfonyl (e.g., aliphatic sulfonyl or aminosulfonyl); sulfinyl (e.g., aliphatic sulfinyl); sulfanyl (e.g., aliphatic sulfanyl); nitro; cyano; halo; hydroxy; mercapto; sulfoxy; urea; thiourea; sulfamoyl; sulfamido; or carbamoyl. Alternatively, heteroaryl can be unsubstituted.

[0041]

[0043] Non-limiting examples of substituted heteroaryls include (halo)heteroaryls (e.g., mono- and di-(halo)heteroaryls); (carboxy)heteroaryls (e.g., (alkoxycarbonyl)heteroaryls); cyanoheteroaryls; aminoheteroaryls (e.g., ((alkylsulfonyl)amino)heteroaryls and ((dialkyl)amino)heteroaryls); (amido)heteroaryls (e.g., aminocarbonylheteroaryls, ((alkylcarbonyl)amino)heteroaryls, ((((alkyl)amino)alkyl)aminocarbonyl)heteroaryls, (((heteroaryl)amino)carbonyl)heteroaryls, ((heteroalicyclic)carbonyl)heteroaryls, and ((alkylcarbonyl)amino)heteroaryls); (cyanoalkyl)heteroaryls; (alkoxy)heteroaryls; (sulfamoyl)heteroaryls. Heteroaryl (e.g., (aminosulfonyl)heteroaryl); (sulfonyl)heteroaryl (e.g., (alkylsulfonyl)heteroaryl); (hydroxyalkyl)heteroaryl; (alkoxyalkyl)heteroaryl; (hydroxy)heteroaryl; ((carboxy)alkyl)heteroaryl; (((dialkyl)amino)alkyl)heteroaryl; (heteroalicyclic)heteroaryl; (alicyclic)heteroaryl; (nitroalkyl)heteroaryl; (((alkylsulfonyl)amino)alkyl)heteroaryl; ((alkylsulfonyl)alkyl)heteroaryl; (cyanoalkyl)heteroaryl; (acyl)heteroaryl (e.g., (alkylcarbonyl)heteroaryl); (alkyl)heteroaryl; or (haloalkyl)heteroaryl (e.g., trihaloalkylheteroaryl).

[0042]

[0044] As used herein, a "heteroaraliphatic" (e.g., heteroaralkyl group) refers to an aliphatic group (e.g., C 1~4 "Aliphatic," "alkyl," and "heteroaryl" are defined above.

[0043]

[0045] As used herein, a "heteroaralkyl" group refers to an alkyl group substituted with a heteroaryl group (e.g., C 1~4 "Heteroaralkyl" refers to alkyl (including carboxyalkyl, hydroxyalkyl, and haloalkyl such as trifluoromethyl), alkenyl, alkynyl, cycloalkyl, (cycloalkyl)alkyl, heterocycloalkyl, (heterocycloalkyl)alkyl, aryl, heteroaryl, alkoxy, cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy, heteroaralkyloxy, aroyl, heteroaroyl, nitro, carboxy, alkoxycarbonyl, alkylcarbonyloxy, aminocarbonyl, and optionally substituted with one or more substituents such as carboxyl, alkylcarbonylamino, cycloalkylcarbonylamino, (cycloalkylalkyl)carbonylamino, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkylalkyl)carbonylamino, heteroarylcarbonylamino, heteroaralkylcarbonylamino, cyano, halo, hydroxy, acyl, mercapto, alkylsulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamido, oxo, or carbamoyl.

[0044]

[0046] As used herein, "cyclic moiety" and "cyclic group" refer to monocyclic, bicyclic, and tricyclic ring systems, including alicyclic, heteroalicyclic, aryl, or heteroaryl, each of which has been previously defined.

[0045]

[0047] As used herein, "bridged bicyclic ring system" refers to a bicyclic heteroalicyclic ring system or a bicyclic alicyclic ring system in which the rings are bridged. Examples of bridged bicyclic ring systems include, but are not limited to, adamantanyl, norbornanyl, bicyclo[3.2.1]octyl, bicyclo[2.2.2]octyl, bicyclo[3.3.1]nonyl, bicyclo[3.3.2]decyl, 2-oxabicyclo[2.2.2]octyl, 1-azabicyclo[2.2.2]octyl, 3-azabicyclo[3.2.1]octyl, and 2,6-dioxa-tricyclo[3.3.1.0]octyl. 3,7 Bridged bicyclic ring systems include alkyl (including carboxyalkyl, hydroxyalkyl, and haloalkyl such as trifluoromethyl), alkenyl, alkynyl, cycloalkyl, (cycloalkyl)alkyl, heterocycloalkyl, (heterocycloalkyl)alkyl, aryl, heteroaryl, alkoxy, cycloalkyloxy, heterocycloalkyloxy, aryloxy, heteroaryloxy, aralkyloxy, heteroaralkyloxy, aroyl, heteroaroyl, nitro, carboxy, alkoxycarbonyl, alkylcarbonyloxy, aminocarbonyl, and the like. The heteroarylcarbonylamino may be optionally substituted with one or more substituents such as aryl, alkylcarbonylamino, cycloalkylcarbonylamino, (cycloalkylalkyl)carbonylamino, arylcarbonylamino, aralkylcarbonylamino, (heterocycloalkyl)carbonylamino, (heterocycloalkylalkyl)carbonylamino, heteroarylcarbonylamino, heteroaralkylcarbonylamino, cyano, halo, hydroxy, acyl, mercapto, alkylsulfanyl, sulfoxy, urea, thiourea, sulfamoyl, sulfamido, oxo, or carbamoyl.

[0046]

[0048] As used herein, an "acyl" group refers to a formyl group or R X -C(O)- (e.g., alkyl-C(O)-, also known as "alkylcarbonyl"), where R X and "alkyl" has been previously defined. Acetyl and pivaloyl are examples of acyl groups.

[0047]

[0049] As used herein, "aroyl" or "heteroaroyl" refers to aryl-C(O)- or heteroaryl-C(O)-, where the aryl and heteroaryl portions of the aroyl or heteroaroyl are optionally substituted as previously defined herein.

[0048]

[0050] As used herein, an "alkoxy" group refers to an alkyl-O- group, where "alkyl" has been previously defined herein.

[0049]

[0051] As used herein, a "carbamoyl" group refers to a group having the structure -O-CO-NR X R Y or -NR X -CO-OR Z where R X and R Y is defined above, and R Z can be aliphatic, aryl, araliphatic, heteroalicyclic, heteroaryl, or heteroaraliphatic.

[0050]

[0052] As used herein, a "carboxy" group refers to -COOH when used as a terminal group; or -OC(O)-, or -C(O)O- when used as an internal group.

[0051]

[0053] As used herein, an ester is an ester when used as a terminal group. X or -COOR when used as an internal group X - refers to where R X is defined above.

[0052]

[0054] As used herein, formate refers to —OC(O)H.

[0053]

[0055] As used herein, acetate is —OC(O)RX where R X is defined above.

[0054]

[0056] As used herein, a "haloaliphatic" group refers to an aliphatic group substituted with one to three halogens. For example, the term haloalkyl includes the group -CF.

[0055]

[0057] As used herein, a "mercapto" or a "sulfhydryl" group refers to --SH.

[0056]

[0058] As used herein, a "sulfo" group is -SO3H when used terminally, or -SO3R X , or S(O)3- when used internally.

[0057]

[0059] As used herein, a "sulfamido" group has the structure -NR when used terminally. X -S(O)2-NR Y R Z , and -NR when used internally X -S(O)2-NR Y - refers to where R X , R Y , and R Z is defined above.

[0058]

[0060] As used herein, a "sulfamoyl" group refers to a group having the structure -OS(O)-NR Y R Z where R Y , and R Z is defined above.

[0059]

[0061] As used herein, a "sulfonamide" group has the structure -S(O)-NR when used terminally. X R Y , or -NR X -S(O)2-R Z or -S(O)2-NR when used internallyX - or -NR X -S(O)2-, where R X , R Y , and R Z is defined above.

[0060]

[0062] As used herein, a "sulfanyl" group is defined as -SR when used terminally. X , and when used internally refers to -S-, where R X is defined above. Examples of sulfanyl include aliphatic-S-, alicyclic-S-, aryl-S-, and the like.

[0061]

[0063] As used herein, a "sulfinyl" group when used terminally is -S(O)-R X , and when used internally refers to -S(O)-, where R X is defined above. Examples of sulfinyl groups include aliphatic -S(O)-, aryl-S(O)-, (alicyclic (aliphatic))-S(O)-, cycloalkyl-S(O)-, heteroalicyclic-S(O)-, heteroaryl-S(O)-, and the like.

[0062]

[0064] As used herein, a "sulfonyl" group refers to a group that is -S(O)-R when used terminally. X and when used internally refers to -S(O)2-, where R X is defined above. Examples of sulfonyl groups include aliphatic -S(O)-, aryl-S(O)-, (alicyclic(aliphatic))-S(O)-, alicyclic-S(O)-, heteroalicyclic-S(O)-, heteroaryl-S(O)-, (alicyclic(amido(aliphatic)))-S(O)-, and the like.

[0063]

[0065] As used herein, a "sulfoxy" group refers to a group that, when used terminally, is -OS(O)-R X , or -S(O)-OR X, and when used internally refers to -OS(O)-, or -S(O)-O-, where R X is defined above.

[0064]

[0066] As used herein, a "halogen" or "halo" group refers to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I).

[0065]

[0067] As used herein, "alkoxycarbonyl," encompassed by the term carboxy, used alone or with another group, refers to groups such as alkyl-OC(O)-.

[0066]

[0068] As used herein, "alkoxyalkyl" refers to an alkyl group such as alkyl-O-alkyl-, where alkyl is defined above.

[0067]

[0069] As used herein, "carbonyl" refers to --C(O)--.

[0068]

[0070] As used herein, "oxo" refers to =O.

[0069]

[0071] As used herein, the term "phospho" refers to phosphinates and phosphonates. Examples of phosphinates and phosphonates include -P(O)(R P )2, where R P is aliphatic, alkoxy, aryloxy, heteroaryloxy, (alicyclic)oxy, (heteroalicyclic)oxy, aryl, heteroaryl, alicyclic or amino.

[0070]

[0072] As used herein, an “aminoalkyl” refers to a group having the structure (R X )2N-alkyl-.

[0071]

[0073] As used herein, a "cyanoalkyl" refers to the structure (NC)-alkyl-.

[0072]

[0074] As used herein, a "urea" group has the structure -NR X -CO-NR Y R Z and "thiourea" groups have the structure -NR when used at the terminal end. X -CS-NR Y R Z , and -NR when used internally, respectively. X -CO-NR Y -or-NR X -CS-NR Y - refers to where R X , R Y , and R Z is defined above.

[0073]

[0075] As used herein, a "guanidine" group refers to a group having the structure -N=C(N(R X R Y ))N(R X R Y ) or -NR X -C(=NR X )NR X R Y where R X and R Y is defined above.

[0074]

[0076] As used herein, the term "amidino" group refers to a group having the structure -C=(NR X )N(R X R Y ), where R X and R Y is defined above.

[0075]

[0077] As used herein, the term "vicinal" generally refers to the arrangement of substituents on a group containing two or more carbon atoms, where the substituents are attached to adjacent carbon atoms.

[0076]

[0078] As used herein, the term "geminal" generally refers to the arrangement of substituents on a group containing two or more carbon atoms, wherein the substituents are attached to the same carbon atom.

[0077]

[0079] The terms "terminally" and "internally" refer to the location of a group within a substituent. A group is terminal if it is at the end of the substituent and is not further attached to the remainder of the chemical structure. Carboxyalkyl (i.e., R X An example of a carboxy group used terminally is an alkylcarboxy (e.g., alkyl-C(O)O- or alkyl-OC(O)-) and an alkylcarboxyaryl (e.g., alkyl-C(O)O-aryl- or alkyl-O(CO)-aryl-) are examples of carboxy groups used internally. An example of a carboxy group used terminally is an alkylcarboxy (e.g., alkyl-C(O)O- or alkyl-OC(O)-) and an alkylcarboxyaryl (e.g., alkyl-C(O)O-aryl- or alkyl-O(CO)-aryl-) are examples of carboxy groups used internally.

[0078]

[0080] As used herein, "aliphatic chain" refers to a branched or straight-chain aliphatic group (e.g., an alkyl group, an alkenyl group, or an alkynyl group). A straight-chain aliphatic chain has the structure -[CH] v -, where v is 1 to 12. A branched aliphatic chain is a linear aliphatic chain substituted with one or more aliphatic groups. A branched aliphatic chain has the structure -[CQQ] v where each Q is independently hydrogen (H or -H) or an aliphatic group; provided that Q is an aliphatic group in at least one instance. The term aliphatic chain includes alkyl chains, alkenyl chains, and alkynyl chains, where alkyl, alkenyl, and alkynyl are defined above.

[0079]

[0081] As used herein, the term "protecting group" refers to a moiety or functional group that is introduced into a molecule by chemical modification of the functional group to obtain chemoselectivity in a subsequent chemical reaction. Standard protecting groups are set forth in Wuts and Greene: "Greene's Protective Groups in Organic Synthesis," 4th Ed., Wuts, P.G.M. and Greene, T.W., Wiley-Interscience, New York: 2006.

[0080]

[0082] The term "optionally substituted," unless otherwise specified, means that a group is unsubstituted or substituted with one or more (e.g., 1, 2, 3, 4, or 5) of the substituents listed for that group, which can be the same or different. In certain embodiments, an optionally substituted group is unsubstituted. In certain embodiments, an optionally substituted group has one substituent. In certain embodiments, an optionally substituted group has two substituents. In certain embodiments, an optionally substituted group has three substituents. In certain embodiments, an optionally substituted group has four substituents. In certain embodiments, an optionally substituted group has 1 to 2, 1 to 3, 1 to 4, or 1 to 5 substituents. When multiple substituents are present, each substituent is independently selected unless otherwise specified. For example, each (C1-C4 alkyl) substituent in the group -N(C1-C4 alkyl)(C1-C4 alkyl) may be selected independently of each other to produce a group such as -N(CH3)(CH2CH3).

[0081]

[0083] As used herein, the term "substituted," whether preceded by the term "optionally" or not, generally refers to the replacement of a hydrogen atom in a given structure with a specified substituent radical. Specific substituents are described above in the definitions and below in the description of compounds and their examples. Unless otherwise specified, an optionally substituted group may have a substituent at each substitutable position of the group, and when two or more positions in any given structure may be substituted with two or more substituents selected from a specified group, the substituents may be the same or different at each position. A ring substituent, such as a heterocycloalkyl, can be bonded to another ring, such as a cycloalkyl, to form a spiro-bicyclic ring system, e.g., both rings share one common atom. Non-limiting examples of spiro-heterocycloalkyl include:

[0084] [ka] Spiro compounds represented by overlapping rings indicate that the rings can be attached at any vertex. For example, a spiro group [ka] In the formula (I), the two rings can be joined at any of the three available vertex atoms on either ring.

[0082]

[0085] One skilled in the art will recognize that combinations of substituents envisioned by this description are those that result in the formation of stable or chemically feasible compounds.

[0083]

[0086] As used herein, the phrase "stable or chemically feasible" refers to a compound that does not change substantially when subjected to conditions that allow for the production, detection, and recovery, purification, and use of the compounds for one or more of the purposes disclosed herein. In certain embodiments, a stable compound or a chemically feasible compound is one that does not change substantially when kept at a temperature of 40° C. or less in the absence of moisture or other chemically reactive conditions for at least one week.

[0084]

[0087] Unless a specific isotope of an element is indicated in a formula, the present disclosure includes all isotopologues of the compounds disclosed herein, for example, deuterated derivatives of the compounds (where H can be 2H, i.e., D). Isotopologues can have isotopic substitution at any or all positions in the structure, or can have atoms present at natural abundance at any or all positions in the structure.

[0085]

[0088] The present disclosure also includes any enantiomeric or diastereomeric forms of the compounds described herein, and all stereochemical forms, including cis / trans or E / Z isomers. Unless stereochemistry is explicitly indicated in a chemical structure or name, the structure or name is intended to encompass all possible stereoisomers of the depicted compound. Furthermore, when a specific stereochemical form is depicted, it is understood that all other stereochemical forms, as well as general non-stereospecific forms and mixtures of the disclosed compounds in any ratio (including mixtures of two or more stereochemical forms of the disclosed compounds in any ratio), are also described and encompassed by the present disclosure, and thus encompass racemic, non-racemic, enantiomerically enriched, and scalemic mixtures of the compounds. Compositions comprising the disclosed compounds, including compositions of substantially pure compounds containing their specific stereochemical forms, are also contemplated. Compositions comprising mixtures of the disclosed compounds in any ratio (including compositions comprising mixtures of two or more stereochemical forms of the disclosed compounds in any ratio) are also encompassed by the present disclosure, and thus racemic, non-racemic, enantiomerically enriched, and scalenic mixtures of the compounds are encompassed by the present disclosure. When stereochemistry is explicitly depicted for one or more portions of a molecule but not for another portion or portions of the molecule, the structure is intended to encompass all possible stereoisomers of the portion or portions where stereochemistry is not explicitly depicted.

[0086]

[0089] The present disclosure also encompasses all tautomers of the compounds described herein.

[0087]

[0090] The present disclosure is intended to encompass all salts of the compounds described herein, as well as methods of using such salts of the compounds. In one embodiment, the salts of the compounds include pharmaceutically acceptable salts. Pharmaceutically acceptable salts are salts that can be administered to humans and / or animals as drugs or pharmaceuticals and that retain at least some of the biological activity of the free compound (neutral or non-salt compound) after administration. The desired salt of a basic compound can be prepared by methods known to those skilled in the art by treating the compound with an acid. Examples of inorganic acids include, but are not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Examples of organic acids include, but are not limited to, formic acid, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, sulfonic acid, and salicylic acid. Salts of basic compounds with amino acids, such as aspartate and glutamate, can also be prepared. The desired salt of an acidic compound can be prepared by treating the compound with a base using methods known to those skilled in the art. Examples of inorganic salts of acidic compounds include, but are not limited to, alkali metal and alkaline earth salts, such as sodium, potassium, magnesium, and calcium salts; ammonium salts; and aluminum salts. Examples of organic salts of acidic compounds include, but are not limited to, procaine, dibenzylamine, N-ethylpiperidine, N,N'-dibenzylethylenediamine, and triethylamine salts. Salts of acidic compounds with amino acids, such as lysine salts, can also be prepared. For a list of pharmaceutically acceptable salts, see, for example, PH Stahl and CG Wermuth (eds.) "Handbook of Pharmaceutical Salts, Properties, Selection and Use" Wiley-VCH, 2011 (ISBN: 978-3-90639-051-2). Some pharmaceutically acceptable salts are also disclosed in Berge, J. Pharm. Sci. 66:1 (1977).

[0088]

[0091] As used herein, the term "about" means within ±10% of a value. For example, a dose of about 100 mg / kg indicates that the dose can be from 90 mg / kg to 110 mg / kg. As a further example, an amount of an additional therapeutic agent in the range of about 50% to about 100% indicates that the amount of additional therapeutic agent ranges from 45-55% to 90-110%. Those of skill in the art will understand the range and application of the term "about" when used to describe other values ​​disclosed herein.

[0089]

[0092] Unless otherwise stated, structures depicted herein are also intended to include all isomeric (e.g., enantiomeric, diastereomeric, and geometric (or conformational)) forms of the structure; for example, the (R)- and (S)-configuration for each asymmetric center, the (Z)- and (E)-double bond isomers, and the (Z)- and (E)-conformational isomers. Thus, single stereochemical isomers as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the present compounds are within the scope of this specification. Alternatively, as used herein, "enantiomeric excess (ee)" refers to a dimensionless molar ratio that represents the purity of a chiral material containing, for example, a single stereocenter. For example, an enantiomeric excess of 0 would indicate a racemate (e.g., a 50:50 mixture of enantiomers, or one enantiomer in excess of the other). As a further example, an enantiomeric excess of 99 would indicate a nearly stereochemically pure enantiomeric compound (i.e., one enantiomer is in large excess over the other). Percentage enantiomeric excess, % ee = ([(R)-compound] - [(S)-compound]) / ([(R)-compound] + [(S)-compound]) × 100, where (R)-compound > (S)-compound; or % ee = ([(S)-compound] - [(R)-compound]) / ([(S)-compound] + [(R)-compound]) × 100, where (S)-compound > (R)-compound. Furthermore, as used herein, "diastereomeric excess (de)" refers to a dimensionless molar ratio that represents the purity of a chiral substance containing two or more stereocenters. For example, a diastereomeric excess of 0 would indicate an equimolar mixture of diastereoisomers. As a further example, a diastereomeric excess of 99 would indicate a nearly stereochemically pure diastereomeric compound (i.e., one diastereomer is in large excess over the other). Diastereomeric excess can be calculated in a similar manner to ee. As will be understood by those skilled in the art, de is usually reported as percent de (% de). % de can be calculated in a similar manner to % ee.

[0090]

[0093] In certain embodiments, the compounds or inhibitors described herein have an ee, de, %ee, or %de range of 90-100. In certain embodiments, the compounds or inhibitors described herein have an ee, de, %ee, or %de range of 95-100. In certain embodiments, the compounds or inhibitors described herein have an ee, de, %ee, or %de range of 97-100. In certain embodiments, the compounds or inhibitors described herein have an ee, de, %ee, or %de range of 98-100. In certain embodiments, the compounds or inhibitors described herein have an ee, de, %ee, or %de range of 99-100.

[0091]

[0094] In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 1. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 2. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 3. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 4. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 5. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 6. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 7. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 8. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 9. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 10. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 11. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 12. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 13. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 14. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 15. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 16. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 17. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 18.In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 19. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 20. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 21. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 22. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 23. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 24. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 25. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 26. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 27. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 28. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 29. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 30. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 31. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 32. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 33. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 34. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 35. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 36.In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 37. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 38. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 39. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 40. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 41. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 42. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 43. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 44. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 45. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 46. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 47. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 48. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 49. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 50. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 51. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 52. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 53. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 54.In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 55. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 56. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 57. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 58. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 59. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 60. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 61. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 62. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 63. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 64. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 65. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 66. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 67. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 68. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 69. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 70. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 71. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 72.In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 73. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 74. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 75. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 76. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 77. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 78. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 79. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 80. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 81. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 82. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 83. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 84. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 85. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 86. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 87. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 88. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 89. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 90.In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 91. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 92. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 93. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 94. In one embodiment of a compound or inhibitor described herein, ee, de, %ee, or %de is 9. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 96. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 97. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 98. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 99. In one embodiment of a compound or inhibitor described herein, the ee, de, %ee, or %de is 100. In certain embodiments, a compound or inhibitor described in Table 1 herein has the ee, de, %ee, or %de as described in this paragraph. In certain embodiments, a compound or inhibitor described in the Examples and / or Biological Examples has the ee, de, %ee, or %de as described in this paragraph. Unless otherwise specified, all tautomers of the compounds herein are within the scope of this specification. Additionally, unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms, for example, the replacement of hydrogen with deuterium or tritium, or 13 C- or 14 Compounds having the present structures except for the replacement of a carbon by a C-enriched carbon are within the scope of this specification. Such compounds are useful, for example, as analytical tools or probes in biological assays or as therapeutic agents.

[0092]

[0095] As used herein, the term "&1" means that a compound containing the designation "&1" at a particular chemical element or atom (e.g., carbon) within that compound was prepared as a mixture of two stereoisomers at the indicated chemical element or atom (e.g., a diastereomeric mixture having de or % de as described above).

[0093]

[0096] Chemical structures and nomenclature are from ChemDraw, version 19.0, Cambridge, MA.

[0094]

[0097] It is noted that the use of descriptors such as "first," "second," "third," etc. are used to distinguish between separate elements (e.g., solvents, reaction steps, processes, reagents, etc.) and may or may not refer to the relative order or relative chronology of the elements being described.

[0095]

[0098] As used herein, the phrase "stable or chemically feasible" refers to a compound that does not change substantially when subjected to conditions that allow for the production, detection, and recovery, purification, and use of the compounds for one or more of the purposes disclosed herein. In certain embodiments, a stable compound or a chemically feasible compound is one that does not change substantially when kept at a temperature of 40° C. or less in the absence of moisture or other chemically reactive conditions for at least one week.

[0096]

[0099] The term "effective amount" of an agent disclosed herein is an amount sufficient to accomplish a specifically described purpose. In certain embodiments, an "effective amount" can be determined empirically and routinely for the described purpose. In certain embodiments, an "effective amount" or a "sufficient amount" of an agent is an amount sufficient to produce a desired biological effect, such as a beneficial result, including a beneficial clinical result. In certain embodiments, the term "effective amount" refers to an amount of an agent effective to "treat" a disease or disorder in an individual (e.g., a mammal such as a human).

[0097]

[0100] The terms "pharmaceutical formulation" and "pharmaceutical composition" refer to a preparation that is in a form that allows the biological activity of the active ingredient to be effective and that does not contain additional ingredients that are unacceptably toxic to the individual to whom the formulation or composition may be administered. Such a formulation or composition may be sterile.

[0098]

[0101] As used herein, the term "excipient" includes a pharmaceutically acceptable excipient, carrier, vehicle, or stabilizer that is non-toxic to cells or mammals exposed thereto at the dosages and concentrations employed. In certain embodiments, the physiologically acceptable excipient is an aqueous pH buffered solution.

[0099]

[0102] The terms "treating" or "treatment" of a disease refer to carrying out a protocol that may include administering one or more therapeutic agents to an individual (human or otherwise) to obtain a beneficial or desired result in the individual, including a clinical result. In certain embodiments, beneficial or desired clinical results include, but are not limited to, alleviation or amelioration of one or more symptoms, reduction in the extent of the disease, a stable (i.e., not worsening) state of the disease, prevention of disease spread, delay or slowing of disease progression, improvement or reduction in disease symptoms, and remission (whether partial or total). In certain embodiments, "treatment" can also mean prolonging survival as compared to the expected survival of an individual not receiving treatment. In certain embodiments, "treating" and "treatment" may occur by administration of a single dose of one or more therapeutic agents, or may occur over the administration of a series of doses of one or more therapeutic agents. In certain embodiments, "treating" or "treatment" does not require complete alleviation of signs or symptoms, and does not require a cure. In certain embodiments, "treatment" may also refer to clinical intervention, such as administering to an individual one or more therapeutic agents designed to alter the natural course of the individual or cell being treated (i.e., to alter the course of the individual or cell that would occur in the absence of clinical intervention). In certain embodiments, the term "therapeutic agent" may refer to a CTM drug that induces proteolysis of a target protein, wherein the target protein is selected from the group consisting of Bruton's tyrosine kinase (BTK); tyrosine-protein kinase (ITK / TSK); bromodomain-containing protein 4 (BRD4); FMS-like tyrosine kinase 3 (FLT-3); Brg / Brahma-associated factor (BAF complex); inducible myeloid leukemia cell differentiation protein (MCL-1); signal transducer and activator of transcription 3 (STAT3); barrier to autointegration factor (BAF); and BCR-ABL, or a composition thereof.In certain embodiments, the target protein is selected from the group consisting of SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2), fibroblast growth factor receptor (FGFR), FGFR1 fusion, FGFR3 fusion, mouse double minute 2 homolog (MDM2), SARS-COV2 protein (e.g., Mpro, or nsp5), phosphoinositide 3-kinase (PI3K) delta, mitogen-activated protein kinase kinase (MEK), histone-lysine N-methyltransferase 2A (MLL), and mucosal-associated lymphoid tissue lymphoma translocation protein 1 (MALT1).

[0100]

[0103] The terms "individual," "patient," or "subject" refer to mammals. In certain embodiments, "mammals" for treatment include humans; non-human primates; domestic and farm animals; and zoo animals, sport animals, or pets, such as dogs, horses, rabbits, cows, pigs, hamsters, gerbils, mice, ferrets, rats, cats, etc. In some embodiments, the individual or subject is human.

[0101] Heterobifunctional Compounds

[0104] Heterobifunctional compounds are provided herein. In certain embodiments, the heterobifunctional compounds comprise at least two moieties, one of which is capable of specifically binding to a target protein. In certain embodiments, the target protein is selected from the group consisting of BTK; ITK / TSK; BRD4; FLT-3; BAF; BAF complex; MCL-1; STAT3; and BCR-ABL. In certain embodiments, the target protein is selected from the group consisting of CDK4, CDK6, SHP-2, FGFR1, FGFR3, FGFR1 fusion, FGFR3 fusion, MDM2, TRIM24, SARS-COV2, PI3K, PI3K delta, MEK, BCR-ABL, MLL, and MALT1. In certain embodiments, the target protein is selected from the group consisting of CDK4, CDK6, SHP-2, FGFR1, FGFR3, FGFR1 fusion, FGFR3 fusion, MDM2, TRIM24, SARS-COV2, PI3K, PI3K delta, MEK, BCR-ABL, MLL, MALT1, IRAK1, and kinases (e.g., broad spectrum). [ka] can recruit a ubiquitin ligase to degrade the target protein. In certain embodiments, the ubiquitin ligase is an E3 ligase. In certain embodiments, the ubiquitin ligase is cereblon (CRBN) or includes cereblon as a component.

[0102]

[0105] In certain embodiments, the compounds provided herein include the compounds described and pharmaceutically acceptable salts, stereoisomers, tautomers, and / or mixtures thereof.

[0103]

[0106] In certain embodiments, there is provided a compound of formula (I) or a stereoisomer and / or pharmaceutically acceptable salt thereof:

[0104]

[0107] In certain embodiments, Y is arylene, heteroaryl, heteroaralkyl, heteroarylene, heterocycle, heterocycloalkyl, or heterocycloalkylaryl, wherein each of the arylene, heteroaryl, heteroaralkyl, heteroarylene, heterocycle, heterocycloalkyl, or heterocycloalkylaryl is optionally substituted. In certain embodiments, the Y moiety is capable of binding to a target protein selected from the group consisting of Bruton's tyrosine kinase (BTK); tyrosine-protein kinase (ITK / TSK); bromodomain-containing protein 4 (BRD4); FMS-like tyrosine kinase 3 (FLT-3); Brg / Brahma-associated factor (BAF complex); inducible myeloid leukemia cell differentiation protein (McL-1); signal transducer and activator of transcription 3 (STAT3); barrier to autointegration factor (BAF); BCR-ABL; MLL; MALT1; IRAK1; and kinases, bringing it into proximity with an E3 ligase for protein ubiquitination and degradation.

[0105]

[0108] In one embodiment, compounds of formula (I), and stereoisomers and pharmaceutically acceptable salts thereof: [ka] is provided herein.

[0106]

[0109] In formula (I), W is -CH or N. In certain embodiments, W is -CH. In certain embodiments, W is -N.

[0107]

[0110] In formula (I), Z is [ka] is selected from the group consisting of:

[0108]

[0111] In formula (I), Z is [ka] is selected from the group consisting of:

[0109]

[0112] In Formula (I), L is a linker group. In certain embodiments, the linker group consists of 3 to 40 carbon atoms, including one or more acyclic and / or cyclic moieties, where one or more carbon atoms can be optionally substituted with a heteroatom selected from O, N, S, and P, or the linker group includes 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 ethylene glycol units.

[0110]

[0113] In formula (I), Y is a target binding moiety that binds to a target protein to be degraded by the compound. In certain embodiments, Y is arylene, heteroaryl, heteroaralkyl, heteroarylene, heterocycle, heterocycloalkyl, or heterocycloalkylaryl, wherein each of the arylene, heteroaryl, heteroaralkyl, heteroarylene, heterocycle, heterocycloalkyl, or heterocycloalkylaryl is optionally substituted.

[0111]

[0114] In certain embodiments, a compound of formula (II), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0112]

[0115] In certain embodiments, a compound of formula (III), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0113]

[0116] In certain embodiments, a compound of formula (IV), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0114]

[0117] In certain embodiments, a compound of formula (V), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0115]

[0118] In certain embodiments, a compound of formula (VI), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0116]

[0119] In certain embodiments, a compound of formula (VII), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0117]

[0120] In certain embodiments, a compound of formula (VIII), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0118]

[0121] In certain embodiments, a compound of formula (IX), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0119]

[0122] In certain embodiments, a compound of formula (X), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0120]

[0123] In certain embodiments, a compound of formula (XI), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0121]

[0124] In certain embodiments, a compound of formula (XII), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0122]

[0125] In certain embodiments, a compound of formula (XIII), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0123]

[0126] In certain embodiments, a compound of formula (XIV), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0124]

[0127] In certain embodiments, a compound of formula (XV), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0125]

[0128] In certain embodiments, a compound of formula (XVI), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0126]

[0129] In certain embodiments, a compound of formula (XVII), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0127]

[0130] In certain embodiments, a compound of formula (XVIII), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0128]

[0131] In certain embodiments, a compound of formula (XIX), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0129]

[0132] In certain embodiments, a compound of formula (XX), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0130]

[0133] In certain embodiments, a compound of formula (XXI), or a stereoisomer and / or a pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0131]

[0134] In certain embodiments, a compound of formula (XXII), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0132]

[0135] In certain embodiments, a compound of formula (XXIII), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0133]

[0136] In certain embodiments, a compound of formula (XXIV), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0134]

[0137] In certain embodiments, a compound of formula (XXV), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0135]

[0138] In certain embodiments, a compound of formula (XXVI), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0136]

[0139] In certain embodiments, a compound of formula (XXVII), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0137]

[0140] In certain embodiments, a compound of formula (XXVIII), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0138]

[0141] In certain embodiments, a compound of formula (XXIX), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] is provided herein, where the variables are described below.

[0139]

[0142] In certain embodiments of any compound of Formulas (I-XXIX), Y is [ka] [ka] [ka] In certain embodiments, R 1 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, haloalkyl, heteroaryl, cyano, —C(O)alkyl, —C(O)aryl, or —C(O)heteroaryl. 2 is hydrogen or halogen. 1 is absent or -O-, -C(O)-, -C(O)-NH-, -C(O)-N(CH3)-, -C(O)-NH-R 4a -, -CH(A 2a)-, -N(alkyl)-, -alkyl-. In certain embodiments, A 2 is absent or -C(H)(A 2a In certain embodiments, A 2a is hydrogen, alkyl, aryl, heterocycle, or heteroaryl. 3 is a bond. In certain embodiments, R 3 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, haloalkyl, heteroaryl, cyano, —C(O)alkyl, —C(O)aryl, or —C(O)heteroaryl. 4 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, haloalkyl, heteroaryl, cyano, —C(O)alkyl, —C(O)aryl, —C(O)heteroaryl, or R 5 is an alkylene bonded to form a substituted cycloalkyl. 5 is hydrogen or R 4 is an alkylene bonded to form a substituted cycloalkyl. 5 and R 4 forms a substituted cycloalkyl. In certain embodiments, the cycloalkyl is substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, haloalkyl, heteroaryl, cyano, —C(O)alkyl, —C(O)aryl, —C(O)heteroaryl, and halogen. In certain embodiments, R 6 is hydrogen or alkyl. In certain embodiments, R 1 is —H. In certain embodiments, R 2 is —H. In certain embodiments, A 1 is —C(O)—. In certain embodiments, A 1 is —C(O)—NH—. In certain embodiments, A1 is -CH2-. In certain embodiments, A 1 is —N(CH)—. In certain embodiments, A 1 is —O—. In certain embodiments, A 1 is —C(O)—N(CH)—. In certain embodiments, A 1 is -C(O)-NH-phenol-. In certain embodiments, A 2 is -CH2-. In certain embodiments, A 2 is -CH2CH3-. In certain embodiments, A 2 is —CH(CH)—. In certain embodiments, A 2 is -CH(phenyl)-.

[0140]

[0143] In certain embodiments, compounds of Formulas (I), and (II-XXIX) are provided herein, wherein Y is: [ka] In certain embodiments, R 1 R 2 and R 5 is H. In certain embodiments, R 3 , R 4 , and R 6 Each of these is CH3.

[0141]

[0144] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] is.

[0142]

[0145] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] is.

[0143]

[0146] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] is.

[0144]

[0147] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] is.

[0145]

[0148] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] is.

[0146]

[0149] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] is.

[0147]

[0150] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] is.

[0148]

[0151] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] is.

[0149]

[0152] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] is.

[0150]

[0153] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] is.

[0151]

[0154] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is B-Raf.

[0152]

[0155] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is B-Raf.

[0153]

[0156] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is B-Raf.

[0154]

[0157] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is B-Raf.

[0155]

[0158] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is B-Raf.

[0156]

[0159] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is B-Raf.

[0157]

[0160] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In a specific embodiment, the target is FLT3.

[0158]

[0161] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is CDK4. In certain embodiments, the target is CDK6.

[0159]

[0162] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is CDK4. In certain embodiments, the target is CDK6.

[0160]

[0163] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In a specific embodiment, the target is SHP-2.

[0161]

[0164] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In a specific embodiment, the target is SHP-2.

[0162]

[0165] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In a specific embodiment, the target is SHP-2.

[0163]

[0166] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is an FGFR1 fusion. In certain embodiments, the target is an FGFR3 fusion.

[0164]

[0167] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is MDM2.

[0165]

[0168] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is MDM2.

[0166]

[0169] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is MDM2.

[0167]

[0170] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In a particular embodiment, the target is TRIM24.

[0168]

[0171] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is SARS-COV2. In certain embodiments, the protein is SARS-COV2 Mpro or nsp5.

[0169]

[0172] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is SARS-COV2. In certain embodiments, the target is SARS-COV2. In certain embodiments, the protein is SARS-COV2 Mpro or nsp5.

[0170]

[0173] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is SARS-COV2. In certain embodiments, the target is SARS-COV2. In certain embodiments, the protein is SARS-COV2 Mpro or nsp5.

[0171]

[0174] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is SARS-COV2. In certain embodiments, the target is SARS-COV2. In certain embodiments, the protein is SARS-COV2 Mpro or nsp5.

[0172]

[0175] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is SARS-COV2. In certain embodiments, the target is SARS-COV2. In certain embodiments, the protein is SARS-COV2 Mpro or nsp5.

[0173]

[0176] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is PI3K delta.

[0174]

[0177] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is MEK.

[0175]

[0178] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is MEK.

[0176]

[0179] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is MEK.

[0177]

[0180] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is MEK.

[0178]

[0181] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In a specific embodiment, the target is BCR-ABL.

[0179]

[0182] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In a specific embodiment, the target is BCR-ABL.

[0180]

[0183] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In a specific embodiment, the target is BCR-ABL.

[0181]

[0184] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is MLL.

[0182]

[0185] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In a specific embodiment, the target is MALT1.

[0183]

[0186] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In a specific embodiment, the target is MALT1.

[0184]

[0187] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is IRAK1.

[0185]

[0188] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is a kinase. In certain embodiments, the target is one or more kinases. In certain embodiments, the target is multiple kinases.

[0186]

[0189] In certain embodiments, provided herein are compounds of Formula (I), wherein Y is: [ka] In certain embodiments, the target is a kinase. In certain embodiments, the target is one or more kinases. In certain embodiments, the target is multiple kinases.

[0187]

[0190] In certain embodiments, a compound of formula (Ia), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0188]

[0191] In certain embodiments, a compound of formula (Ib), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0189]

[0192] In certain embodiments, a compound of formula (Ib1), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0190]

[0193] In certain embodiments, a compound of formula (Ic), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0191]

[0194] In certain embodiments, a compound of formula (Id), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0192]

[0195] In certain embodiments, a compound of formula (Ie), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0193]

[0196] In certain embodiments, a compound of formula (If), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0194]

[0197] In certain embodiments, a compound of formula (IIa), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0195]

[0198] In certain embodiments, a compound of formula (IIb), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0196]

[0199] In certain embodiments, a compound of formula (IIc), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0197]

[0200] In certain embodiments, a compound of formula (IId), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0198]

[0201] In certain embodiments, a compound of formula (IIe), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0199]

[0202] In certain embodiments, a compound of formula (IIf), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0200]

[0203] In certain embodiments, a compound of formula (IIg), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0201]

[0204] In certain embodiments, a compound of formula (IIh), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0202]

[0205] In certain embodiments, a compound of formula (IIi), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0203]

[0206] In certain embodiments, a compound of formula (IIj), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0204]

[0207] In certain embodiments, a compound of formula (IIk), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0205]

[0208] In certain embodiments, a compound of formula (IIm), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0206]

[0209] In certain embodiments, a compound of formula (IIn), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0207]

[0210] In certain embodiments, a compound of formula (IIn′), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0208]

[0211] In certain embodiments, a compound of formula (IIo), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0209]

[0212] In certain embodiments, a compound of formula (IIp), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0210]

[0213] In certain embodiments, a compound of formula (IIq), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0211]

[0214] In certain embodiments, a compound of formula (IIr), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0212]

[0215] In certain embodiments, compounds of formula (IIs), or stereoisomers and / or pharmaceutically acceptable salts thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0213]

[0216] In certain embodiments, a compound of formula (IIt), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0214]

[0217] In certain embodiments, a compound of formula (IIu), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0215]

[0218] In certain embodiments, a compound of formula (IIv), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0216]

[0219] In certain embodiments, a compound of formula (IIw), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0217]

[0220] In certain embodiments, a compound of formula (IIx), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0218]

[0221] In certain embodiments, a compound of formula (IIy), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0219]

[0222] In certain embodiments, a compound of formula (IIz), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0220]

[0223] In certain embodiments, a compound of formula (IIaa), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0221]

[0224] In certain embodiments, a compound of formula (IIbb), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0222]

[0225] In certain embodiments, a compound of formula (IIcc), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0223]

[0226] In certain embodiments, a compound of formula (IIdd), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0224]

[0227] In certain embodiments, a compound of formula (IIee), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0225]

[0228] In certain embodiments, a compound of formula (IIff), or a stereoisomer and / or a pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0226]

[0229] In certain embodiments, a compound of formula (IIgg), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0227]

[0230] In certain embodiments, a compound of formula (IIhh), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0228]

[0231] In certain embodiments, a compound of formula (IIii), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0229]

[0232] In certain embodiments, a compound of formula (IIjj), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0230]

[0233] In certain embodiments, a compound of formula (IIkk), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0231]

[0234] In certain embodiments, a compound of formula (IImm), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0232]

[0235] In certain embodiments, a compound of formula (IInn), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0233]

[0236] In certain embodiments, a compound of formula (IIoo), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0234]

[0237] In certain embodiments, a compound of formula (IIpp), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0235]

[0238] In certain embodiments, a compound of formula (IIqq), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by formula W. In certain embodiments, the harness is represented by formula X. In certain embodiments, the harness is represented by formula Y. In certain embodiments, the harness is represented by formula Z. In certain embodiments, the harness is represented by formula α. In certain embodiments, the harness is represented by formula β. In certain embodiments, the harness is represented by formula AA.In certain embodiments, the harness is represented by formula BB. In certain embodiments, the harness is represented by formula CC. In certain embodiments, the harness is represented by formula DD. In certain embodiments, the harness is represented by formula EE. In certain embodiments, the harness is represented by formula FF. In certain embodiments, the harness is represented by formula GG. In certain embodiments, the harness is represented by formula HH. In certain embodiments, the harness is represented by formula II. In certain embodiments, the harness is represented by formula JJ. In certain embodiments, the harness is represented by formula KK. In certain embodiments, the harness is represented by formula LL. In certain embodiments, the harness is represented by formula MM. In certain embodiments, the harness is represented by formula NN. In certain embodiments, the harness is represented by formula OO. In certain embodiments, the harness is represented by formula PP. In certain embodiments, the harness is represented by formula QQ. In certain embodiments, the harness is represented by formula RR. In certain embodiments, the harness is represented by formula SS. In certain embodiments, the harness is represented by formula TT. In certain embodiments, the harness is represented by formula UU. In certain embodiments, the harness is represented by formula VV. In certain embodiments, the harness is represented by formula WW. In certain embodiments, the harness is represented by formula XX. In certain embodiments, the harness is represented by formula YY. In certain embodiments, the harness is represented by formula ZZ. In certain embodiments, the harness is represented by formula αα. In certain embodiments, the harness is represented by formula ββ.

[0236]

[0239] In certain embodiments, a compound of formula (IIqq), or a stereoisomer and / or pharmaceutically acceptable salt thereof: [ka] are provided herein, where the variables are described below. In certain embodiments, the left side of the compound is a harness, and the harness is any harness described herein. In certain embodiments, the portion of the compound attached to the left of L is a harness, and the harness is any harness described herein. In certain embodiments, the harness is any of formulas A-β in the table below. In certain embodiments, the harness is any of formulas AA-ββ in the table below. In certain embodiments, the harness is represented by formula A. In certain embodiments, the harness is represented by formula B. In certain embodiments, the harness is represented by formula C. In certain embodiments, the harness is represented by formula D. In certain embodiments, the harness is represented by formula E. In certain embodiments, the harness is represented by formula F. In certain embodiments, the harness is represented by formula G. In certain embodiments, the harness is represented by formula H. In certain embodiments, the harness is represented by formula I. In certain embodiments, the harness is represented by formula J. In certain embodiments, the harness is represented by formula K. In certain embodiments, the harness is represented by formula L. In certain embodiments, the harness is represented by formula M. In certain embodiments, the harness is represented by formula N. In certain embodiments, the harness is represented by formula O. In certain embodiments, the harness is represented by formula P. In certain embodiments, the harness is represented by formula Q. In certain embodiments, the harness is represented by formula R. In certain embodiments, the harness is represented by formula S. In certain embodiments, the harness is represented by formula T. In certain embodiments, the harness is represented by formula U. In certain embodiments, the harness is represented by formula V. In certain embodiments, the harness is represented by...

Claims

1. Compounds of formula (I) 【Chemistry 1】 (In the formula: -NH in formula (I) may be optionally replaced with -CH ; W is CH; Z, 【Chemistry 2】 selected from the group consisting of: an L linker group; optionally the L linker group comprises 3 to 40 carbon atoms, including one or more acyclic and / or cyclic moieties, where one or more carbon atoms may be optionally substituted with a heteroatom selected from O, N, S, and P, or the L linker group comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 ethylene glycol units; where the L linker group is optionally substituted; and Y is a target binding moiety that binds to a target protein that is degraded by the compound. or a stereoisomer thereof or a pharma- ceutically acceptable salt thereof. 【Request 2】 【Chemistry 3】 During the ceremony: W is CH; Z, 【Chemistry 4】 selected from the group consisting of: L is a linker group; Y, 【Chemistry 5】 【Chemistry 6】 【Chemistry 7-1】 【Chemistry 7-2】 【Chemistry 7-3】 is selected from: R １ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, haloalkyl, heteroaryl, cyano, -C(O)alkyl, -C(O)aryl, or -C(O)heteroaryl; R ２ is hydrogen or halogen; A １ is absent, or -O-, -C(O)-, -C(O)-NH-, -C(O)-NH-A ２ａ -, -CH(A ２ａ )-, -N(alkyl)-, -alkyl-; A ２ is absent or -C(H)(A ２ａ )-, where A ２ａ is hydrogen, alkyl, aryl, heterocycle, or heteroaryl; A ３ is a bond; R ３ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, haloalkyl, heteroaryl, cyano, -C(O)alkyl, -C(O)aryl, or -C(O)heteroaryl; R ４ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, haloalkyl, heteroaryl, cyano, -C(O)alkyl, -C(O)aryl, -C(O)heteroaryl, or R ５ is linked to form a substituted cycloalkyl; R ５ is hydrogen or R ４ is an alkylene bonded to form said substituted cycloalkyl; Here, R ５ and R ４ When forms said substituted cycloalkyl, said cycloalkyl is substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, haloalkyl, heteroaryl, cyano, -C(O)alkyl, -C(O)aryl, -C(O)heteroaryl, and halogen; R ６ is hydrogen or alkyl; 2. The compound according to claim 1, or a stereoisomer thereof, or a pharma- ceutically acceptable salt thereof.

3. The L linker group: -L １ -L ２ -L ３ -L ４ -L ５ -L ６ -L ７ -, wherein -L １ - is absent, -N(R ２１ )-; C(R ２２ ) -; C １～８ Alkylene; C ２～８ Alkynylene; Q １ or Q ２ and Each -L ２ -, -L ３ -, -L ４ - and -L ５ - is independently absent; -N(R ２１ )-; C(R ２２ )-;-C(O)-;-O-;-(CH ２ -CH ２ -O) １～８ -;C １～８ Alkylene; C ２～８ Alkynylene; Q １ ;Q ２ or Q ３ and Each -L ６ - and -L ７ - is independently absent; -N(R ２１ )-;-C(R ２２ )-;-C(O)-;-C(O)-N(R ２１ ) -; -N(R ２１ )-C(O); or -C(R ２２ )-C(O)-N(R ２１ ) and Each Q １ is a 3- to 7-membered heterocycloalkylene containing at least one nitrogen; Each Q ２ is a 5- to 13-membered spiro bicyclic heterocycloalkylene containing at least one nitrogen; Each Q ３ is a 3- to 6-membered cycloalkylene; R １０ is H or methyl; R １１ The compound of claim 1 , wherein is H, methyl, aryl, or heteroaryl.

4. 2. The compound of claim 1, wherein the Y moiety is capable of binding to a target protein selected from the group consisting of Bruton's tyrosine kinase (BTK); tyrosine-protein kinase (ITK / TSK); bromodomain-containing protein 4 (BRD4); FMS-like tyrosine kinase 3 (FLT-3); Brg / Brahma-associated factor (BAF complex); inducible myeloid leukemia cell differentiation protein (MCL-1); signal transducer and activator of transcription 3 (STAT3); barrier to autointegration factor (BAF); and BCR-ABL, bringing it into proximity with an E3 ligase, resulting in ubiquitination and degradation of the protein.

5. 2. The compound of claim 1, wherein Y is arylene, heteroaryl, heteroaralkyl, heteroarylene, heterocycle, heterocycloalkyl, or heterocycloalkylaryl, wherein each of the arylene, heteroaryl, heteroaralkyl, heteroarylene, heterocycle, heterocycloalkyl, or heterocycloalkylaryl is optionally substituted.

6. R １ is H, R ２ is H, A １ does not exist, —C(O)—, —C(O)—NH—, —CH ２ -, -N(CH ３ )-, -O-, or -C(O)-NH-phenol-; A ２ does not exist, -CH ２ --, --CH ２ CH ３ -, -CH(CH ３ )-, or -CH(phenyl)-; A ３ is a bond, or Y, 【Chemistry 8】 2. The compound of claim 1 ,

7. A ３ When is a bond, R １ , R ２ , and R ５ each of is —H; or A ３ When is a bond, R ３ , R ４ , and R ６ Each of ３ That is, The compound of claim 1.

8. Y, 【Chemistry 9】 【Chemistry 10】 【Chemistry 11】 【Chemistry 12】 Or, 【Chemistry 13】 2. The compound of claim 1 ,

9. L, 【Chemistry 14】 At least one -Q represented by １ -, wherein n １ is 1 or 2, and n ２ is 1 or 2, or L, 【Chemistry 15】 or containing at least one -Q 1 - selected from the group consisting of: L, 【Chemistry 16】 and n 3 is 1 or 2; or L, 【Chemistry 17】 or containing at least one -Q 2 - represented by L, 【Chemistry 18】 wherein n 4 is 1 or 2, n 5 is 1 or 2, and n 6 is 1 or 2; or L, 【Chemistry 19】 or containing at least one -Q 2 - represented by L, 【Chemistry 20】 wherein n 8 is 1 or 2; or L, 【Chemistry 21】 or containing at least one -Q 2 - represented by L, 【Chemical 22】 wherein n 18 and n 19 are 2 or piperidinyl; or when n 18 is 2, n 19 is 3 or azepanyl; or when n 18 is 3, n 19 is 2 or azepanyl; or L, 【Chemistry 23】 or containing at least one -Q 2 - represented by L, 【Chemistry 24】 wherein n 22 is 0 to 2; n 23 is 0 to 2, and n 24 is 1 or 2, and optionally, when n 22 is 2, then n 23 and n 24 are 1; or when n 22 is 2, then each n 23 and n 24 is 2; or L, 【Chemistry 25】 or containing at least one -Q 2 - represented by L, 【Chemistry 26】 or containing at least one -Q 2 - represented by L, 【Chemical 27】 wherein n 1 is 1 or 2 and n 2 is 1 or 2; or L, 【Chemistry 28】 The compound of claim 1, comprising at least one -Q 3 - selected from the group consisting of:

10. L, a.-Q １ -N(Me)-CH ２ -Q １ -C(O)-; b.-N(Me)-Q １ -CH ２ -Q １ -C(O)-; c.-Q ２ -CH ２ -Q １ -C(O)-; d.-Q １ -CH ２ -Q １ -C(O)-; e.-Q １ -Q １ -C(O)-; f.-Q １ -CH ２ -N(Me)-Q １ -C(O)-; g.-Q １ -CH ２ -Q １ -CH ２ -C(O)-N(Me)-; h.-Q １ -N(Me)-CH ２ -Q １ -C(O)-; i.-Q １ -CH ２ -Q １ -; j.-Q １ -CH ２ -Q ２ -; k.-Q １ -CH ２ -Q １ -N(H)-; l.-Q １ -CH ２ -Q ２ -N(H)-; m.-Q １ -CH ２ -Q １ -CH ２ -Q １ -; n.-Q １ -CH ２ -CH ２ -Q １ -; o.-Q １ -CH ２ -CH ２ -Q ２ -; p.-Q １ -C(O)-Q １ -; q.-Q １ -C(O)-Q ２ -; r.-Q １ -CH ２ -Q １ -N(Me)-C(O)-; s.-CH ２ -CH ２ -CH ２ -CH ２ -Q １ -C(O)-; t.-Q １ -CH ２ -Q １ -C(O)-; u.-Q １ -C(O)-; v.-Q １ -C(O)-Q １ -C(C ６ H ５ )-; w.-C≡CCH ２ -Q １ -C(O)-; x.-Q １ -C(O)-Q ２ -; y.-Q １ -CH ２ -CH ２ -Q ２ -; z.-Q １ -CH ２ -Q １ -N-C(O)-; aa.-CH ２ -CH ２ -CH ２ -Q １ -C(O)-; bb.-Q １ -CH ２ -Q １ -C(Me)-C(O)-N(Me)-; cc.-Q １ -Q １ -C(O)-; dd.-CH ２ -Q １ -; ee.-Q １ -C(O)-Q １ -CH ２ -; ff.-N(H)-(CH ２ ) ５ -C(O)-Q １ -C(C ６ H ５ )-; gg.-N(H)-(CH ２ ) ２ -O-(CH ２ ) ２ -C(O)-Q １ -C(C ６ H ５ )-; hh.-Q １ -(CH ２ ) ３ -C(O)-Q １ -C(C ６ H ５ )-; iiQ ２ !!Q １ (C ６ H ５ )?) jj.-Q ２ --H ２ -C(O)-Q １ -C(C ６ H ５ )-; kk.-Q ２ -(CH ２ ) ３ -C(O)-Q １ -C(C ６ H ５ )-; ll.-Q ２ -(CH ２ ) ２ -C(O)-Q １ -C(C ６ H ５ )-; mm.-(CH ２ ) ６ -Q １ -C(C ６ H ５ )-; nn.-Q １ -Q １ -C(O)-Q １ -C(C ６ H ５ )-; oo.-Q １ -CH ２ -C(O)-Q １ -C(C ６ H ５ )-; pp.-Q １ -(EH ２ ) ２ -C(O)-Q １ -C(C ６ H ５ )-; qq.-Q １ -(CH ２ ) ３ -C(O)-Q １ -C(C ６ H ５ )-; rr.-(CH ２ ) ３ -C(O)-Q １ -C(C ６ H ５ )-; ss.-(CH ２ ) ４ -C(O)-Q １ -C(C ６ H ５ )-; tt.-(CH ２ ) ５ -C(O)-Q １ -C(C ６ H ５ )-; ･･･-(CH ２ ) ６ -C(O)-Q １ -C(C ６ H ５ )-; vv.-(CH ２ ) ３ -Q １ -CH ２ -C(O)-Q １ -C(C ６ H ５ )-; ww.-(CH ２ ) ６ -Q １ -C(C ６ H ５ )-; xx. - (CH ２ ) ６ -Q １ -C(thiazolyl)-; yy.-(CH ２ ) ３ -O-Q ３ -C(O)-Q １ -C(C ６ H ５ )-; zz.-(CH ２ ) ３ -O-(CH ２ ) ２ -C(O)-Q １ -C(C ６ H ５ )-; aaa. -(CH ２ ) ３ -O-(CH ２ ) ２ -C(O)-Q １ -C(thiazolyl)-; bbb. - (CH ２ ) ３ -O-(CH ２ ) ２ -C(O)-Q １ -C(pyrid-2-yl)-; ccc.-(CH ２ ) ４ -Q １ -C(C ６ H ５ )-; ddd.-(CH ２ ) ５ -Q １ -C(C ６ H ５ )-; eee.-(CH ２ ) ６ -Q １ -C(C ６ H ５ )-; fff. - (CH ２ ) ６ -Q １ -C(thiazolyl)-; ggg. - (CH ２ ) ６ -Q １ -C(pyrid-2-yl)-; hhh.-(CH ２ ) ７ -Q １ -C(C ６ H ５ )-; iii.-(CH ２ ) ７ -Q １ -C(Me)-C(O)-N(Me)-; jjj.-N(H)-(CH ２ ) ２ -O-(CH ２ ) ２ -Q １ -C(Me)-C(O)-N(Me)-; kkk.-(CH ２ ) ３ -O-(CH ２ ) ２ -C(O)-Q １ -C(Me)-C(O)-N(Me)-; lll.-N(H)-(CH ２ ) ２ -O-(CH ２ ) ２ -Q １ -C(C ６ H ５ )-; mmm.-N(H)-(CH ２ ) ２ -O-(CH ２ ) ２ -C(O)-Q １ -C(C ６ H ５ )-; nnn.-N(H)-(CH ２ ) ２ -[O-(CH ２ ) ２ ] ２ -C(O)-Q １ -C(C ６ H ５ )-; ooo.-N(H)-(CH ２ ) ２ -[O-(CH ２ ) ２ ] ３ -C(O)-Q １ -C(C ６ H ５ )-; ppp.-N(H)-(CH ２ ) ２ -[O-(CH ２ ) ２ ] ４ -C(O)-Q １ -C(C ６ H ５ )-; qqq.-N(H)-(CH ２ ) ２ -[O-(CH ２ ) ２ ] ５ -C(O)-Q １ -C(C ６ H ５ )-; rrr.-N(H)-(CH ２ ) ２ -[O-(CH ２ ) ２ ] ６ -C(O)-Q １ -C(C ６ H ５ )-; sss.-N(H)-(CH ２ ) ２ -[O-(CH ２ ) ２ ] ７ -C(O)-Q １ -C(C ６ H ５ )-; ttt.-N(H)-(CH ２ ) ２ -[O-(CH ２ ) ２ ] ８ -C(O)-Q １ -C(C ６ H ５ )-; uuu.-N(H)-Q ３ -O-(CH ２ ) ２ -CH ２ -; Yellow ２ ) ３ -Q １ -(CH ２ ) ２ -; www.-C(O)-N(H)-[(CH ２ ) ３ -O] ３ -(CH ２ ) ２ -NH-; xxx.-C(O)-N(H)-[(CH ２ ) ３ -O] ３ -(CH ２ ) ２ -; yyy.-Q １ -C(O)-[(CH ２ ) ２ -O] ３ -(CH ２ ) ２ -NH-; zzz.-Q １ -(CH ２ ) ３ -O-CH ２ -; aaaa.-Q １ -C(O)-(C ６ H ６ )-CH ２ -; bbbb. -Q １ -(2-pyridyl)-O-CH ２ -; cccc. -N(H)-Q ３ -X １ -(2-pyridyl)-O-; dddd. -N(H)-Q ３ -X １ -(4-pyridyl)-; eeee. -N(H)-(CH ２ ) ２ -Q ３ -X １ -(2-pyridyl)-O-CH ２ -; ffff. -CH≡C-(CH ２ ) ２ Q １ - and gggg.-Q １ -, where X is any one selected from １ is oxygen or sulfur, or The L linker group is 【Chemical 29】 【Chemistry 30】 【Chemistry 31】 is selected from the group consisting of 【Chemistry 32】 A compound according to any one of claims 1 to 9, wherein represents a bond to Y.

11. The compound of formula (I): The following formula (II): 【Chemical 33】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (III): 【Chemical 34】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (IV): 【Chemistry 35】 or a stereoisomer thereof or a pharma- ceutically acceptable salt thereof. Below formula (V): 【Chemical 36】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (VI): 【Chemical 37】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (VII): 【Chemical Formula 38】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (VIII): 【Chemical 39】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (IX): 【Chemistry 40】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; Below formula (X): 【Chemistry 41】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XI): 【Chemistry 42】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XII): 【Chemistry 43】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XIII): 【Chemistry 44】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XIV): 【Chemistry 45】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XV): 【Chemistry 46】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XVI): 【Chemistry 47】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XVII): 【Chemistry 48】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XVIII): 【Chemistry 49】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XIX): 【Chemistry 50】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XX): 【Chemistry 51】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XXI): 【Chemistry 52】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XXII): 【Chemistry 53】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XXIII): 【Chemical 54】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XXIV): 【Chemistry 55】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XXV): 【Chemistry 56】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XXVI): 【Chemistry 57】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XXVII): 【Chemistry 58】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XXVIII): 【Chemical Formula 59】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (XXIX): 【Chemistry 60】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (Ia): 【Chemistry 61】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (Ib): 【Chemistry 62】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (Ib1): 【Chemistry 63】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (Ic): 【Chemistry 64】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (Id): 【Chemistry 65】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (Ie): 【Chemistry 66】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (If): 【Chemistry 67】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I1): 【Chemistry 68】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I2): 【Chemistry 69】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I2A): 【Chemistry 70】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I3): 【Chemistry 71】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I3A): 【Chemical 72】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I4): 【Chemical Formula 73】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I5): 【Chemical 74】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I6): 【Chemistry 75】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I7): 【Chemical Formula 76】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I7A): 【Chemical 77】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I8): 【Chemical Formula 78】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I8A): 【Chemical Formula 79】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I9): 【Chemistry 80】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I10): 【Chemistry 81】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I11): 【Chemistry 82】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I12): 【Chemistry 83】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I12A): 【Chemistry 84】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I13): 【Chemistry 85】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I13A): 【Chemistry 86】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I14): 【Chemistry 87】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I15): 【Chemistry 88】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I16): 【Chemistry 89】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I17): 【Chemistry 90】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I17A): 【Chemistry 91】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I18): 【Chemistry 92】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I18A): 【Chemistry 93】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I19): 【Chemistry 94】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I20): 【Chemistry 95】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I21): 【Chemistry 96】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I22): 【Chemistry 97】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I22A): 【Chemistry 98】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I23): 【Chemistry 99】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I23A): 【Chemistry 100】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I24): 【Chemistry 101】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I25): 【Chemistry 102】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I26): 【Chemistry 103】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I27): 【Chemistry 104】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I27A): 【Chemistry 105】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I28): 【Chemistry 106】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I28A): 【Chemistry 107】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I29): 【Chemistry 108】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I30): 【Chemistry 109】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I31): 【Chemistry 110】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I32): 【Chemistry 111】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I32A): 【Chemistry 112】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I33): 【Chemistry 113】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I33A): 【Chemistry 114】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I34): 【Chemistry 115】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I35): 【Chemistry 116】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I36): 【Chemistry 117】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I37): 【Chemistry 118】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I37A): 【Chemistry 119】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I38): 【Chemistry 120】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I38A): 【Chemistry 121】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I39): 【Chemistry 122】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I40): 【Chemistry 123】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I41): 【Chemistry 124】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I42): 【Chemistry 125】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I42A): 【Chemistry 126】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I43): 【Chemistry 127】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I43A): 【Chemistry 128】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I44): 【Chemistry 129】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I45): 【Chemistry 130】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I46): 【Chemistry 131】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I47): 【Chemistry 132】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I47A): 【Chemistry 133】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I48): 【Chemistry 134】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I48A): 【Chemistry 135】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I49): 【Chemistry 136】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I50): 【Chemistry 137】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I51): 【Chemistry 138】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I52): 【Chemistry 139】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I52A): 【Chemistry 140】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I53): 【Chemistry 141】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I53A): 【Chemistry 142】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I54): 【Chemistry 143】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I55): 【Chemistry 144】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I56): 【Chemistry 145】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I57): 【Chemistry 146】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I57A): 【Chemistry 147】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I58): 【Chemistry 148】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I58A): 【Chemistry 149】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I59): 【Chemistry 150】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I60): 【Chemistry 151】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I61): 【Chemistry 152】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I62): 【Chemistry 153】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I62A): 【Chemistry 154】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I63): 【Chemistry 155】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I63A): 【Chemistry 156】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I64): 【Chemistry 157】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I65): 【Chemistry 158】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I66): 【Chemistry 159】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I67): 【Chemistry 160】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I67A): 【Chemistry 161】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I68): 【Chemistry 162】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I68A): 【Chemistry 163】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I69): 【Chemistry 164】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I70): 【Chemistry 165】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I71): 【Chemistry 166】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I72): 【Chemistry 167】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I72A): 【Chemistry 168】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I73): 【Chemistry 169】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I73A): 【Chemistry 170】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I74): 【Chemistry 171】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I75): 【Chemistry 172】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I76): 【Chemistry 173】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I77): 【Chemistry 174】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I77A): 【Chemistry 175】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I78): 【Chemistry 176】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I78A): 【Chemistry 177】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I79): 【Chemistry 178】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I80): 【Chemistry 179】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I81): 【Chemistry 180】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I82): 【Chemistry 181】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I82A): 【Chemistry 182】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I83): 【Chemistry 183】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I83A): 【Chemistry 184】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I84): 【Chemistry 185】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I85): 【Chemistry 186】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I86): 【Chemistry 187】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I87): 【Chemistry 188】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I87A): 【Chemistry 189】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I88): 【Chemistry 190】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I88A): 【Chemistry 191】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I89): 【Chemistry 192】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I90): 【Chemistry 193】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I91): 【Chemistry 194】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I92): 【Chemistry 195】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I92A): 【Chemistry 196】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I93): 【Chemistry 197】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I93A): 【Chemistry 198】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I94): 【Chemistry 199】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I95): 【Chemistry 200】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I96): 【Chemistry 201】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I97): 【Chemistry 202】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I97A): 【Chemistry 203】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I98): 【Chemistry 204】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I98A): 【Chemistry 205】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I99): 【Chemistry 206】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I100): 【Chemistry 207】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I101): 【Chemistry 208】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I102): 【Chemistry 209】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I102A): 【Chemistry 210】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I103): 【Chemistry 211】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I103A): 【Chemistry 212】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I104): 【Chemistry 213】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I105): 【Chemistry 214】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I106): 【Chemistry 215】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I107): 【Chemistry 216】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I107A): 【Chemistry 217】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I108): 【Chemistry 218】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I108A): 【Chemical 219】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I109): 【Chemistry 220】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I110): 【Chemistry 221】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I111): 【Chemical 222】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I112): 【Chemical 223】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I112A): 【Chemical 224】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I113): 【Chemistry 225】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I113A): 【Chemical 226】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The following formula (I114): 【Chemical 227】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; and The following formula (I115): 【Chemical 228】 or a stereoisomer or a pharma- ceutically acceptable salt thereof; The compound of claim 1, which is a compound selected from:

12. The compound according to claim 1, which is a compound selected from the compounds of compound numbers 1 to 485 below, or a stereoisomer thereof, or a pharma- ceutically acceptable salt thereof. 【Hua 229-1】 【Hua 229-2】 【Chemistry 229-3】 【Chemistry 229-4】 【Chemistry 229-5】 【Chemistry 229-6】 【Chemistry 229-7】 【Chemistry 229-8】 【Chemistry 229-9】 【Chemistry 229-10】 【Chemistry 229-11】 【Chemistry 229-12】 【Chemistry 229-13】 【Chemistry 229-14】 【Chemistry 229-15】 【Chemistry 229-16】 【Chemistry 229-17】 【Chemistry 229-18】 【Chemistry 229-19】 【Chemistry 229-20】 【Chemistry 229-21】 【Chemistry 229-22】 【Chemistry 229-23】 【Chemistry 229-24】 【Chemistry 229-25】 【Chemistry 229-26】 【Chemistry 229-27】 【Chemistry 229-28】 【Chemistry 229-29】 【Chemistry 229-30】 【Chemistry 229-31】 【Chemistry 229-32】 【Chemistry 229-33】 【Chemistry 229-34】 【Chemistry 229-35】 【Chemistry 229-36】 【Chemistry 229-37】 【Chemistry 229-38】 【Chemistry 229-39】 【Chemistry 229-40】 【Chemistry 229-41】 【Chemistry 229-42】 【Chemistry 229-43】 【Chemistry 229-44】 【Chemistry 229-45】 【Chemistry 229-46】 【Chemistry 229-47】 【Chemistry 229-48】 【Chemistry 229-49】 【Chemistry 229-50】 【Chemistry 229-51】 【Chemistry 229-52】 【Chemistry 229-53】 【Chemistry 229-54】 【Chemistry 229-55】 【Chemistry 229-56】 【Chemistry 229-57】 【Chemistry 229-58】 【Chemistry 229-59】 【Chemistry 229-60】 【Chemistry 229-61】 【Chemistry 229-62】 【Chemistry 229-63】 【Chemistry 229-64】 【Chemistry 229-65】 【Chemistry 229-66】 【Chemistry 229-67】 【Chemistry 229-68】 【Chemistry 229-69】 【Chemistry 229-70】 【Chemistry 229-71】 【Chemistry 229-72】 【Chemistry 229-73】 【Chemistry 229-74】 【Chemistry 229-75】 【Chemistry 229-76】 【Chemistry 229-77】 【Chemistry 229-78】 【Chemistry 229-79】 【Chemistry 229-80】 【Chemistry 229-81】 【Chemistry 229-82】 【Chemistry 229-83】 【Chemistry 229-84】 【Chemistry 229-85】 【Chemistry 229-86】 【Chemistry 229-87】 【Chemistry 229-88】 【Chemistry 229-89】 【Chemistry 229-90】 【Chemistry 229-91】 【Chemistry 229-92】

13. 13. A method for producing a decomposition compound based on the compound of claim 1, capable of decomposing a target protein in a cell, comprising: A method comprising the step of linking a Y target binding moiety that binds to a target protein to a degron, either directly or via an L linker group, to form said degrading compound.

14. 12. A method for degrading a target protein in a cell, comprising the steps of: preparing a degradation compound for the target protein described in claim 11; and contacting the target protein with the degradation compound.

15. 15. The method of claim 13 or 14, wherein the target protein is selected from the group consisting of FLT3, SHP-2, GLD06, CDK4 / 6, MALT1, BRAF, BCR-ABL, MEK, FGFR1 and FGFR3 and fusions thereof, RET and fusions thereof, BCL-2, PI3K delta, MLL, Aurora A, KRAS, KRAS G12D, KRAS G12C, MDM2, MCL-1, PI3K alpha, eIF4e, KSR, and TRIM24.

16. 15. The method of claim 13 or 14, wherein the Y target binding moiety is capable of binding to a target protein selected from the group consisting of Bruton's tyrosine kinase (BTK); tyrosine-protein kinase (ITK / TSK); bromodomain-containing protein 4 (BRD4); FMS-like tyrosine kinase 3 (FLT-3); Brg / Brahma-associated factor (BAF complex); inducible myeloid leukemia cell differentiation protein (MCL-1); signal transducer and activator of transcription 3 (STAT3); barrier to autointegration factor (BAF); and BCR-ABL.

17. 15. The method of claim 13 or 14, wherein the target protein is selected from the group consisting of CDK4, CDK6, SHP-2, FGFR1, FGFR3, FGFR1 fusion, FGFR3 fusion, MDM2, TRIM24, SARS-COV2 protein, PI3K, PI3K delta, MEK, BCR-ABL, MLL, and MALT1.

18. the target binding moiety Y being 【Chemistry 230】 【Chemistry 231】 【Chemical 232】 is selected from the group consisting of: R １ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, haloalkyl, heteroaryl, cyano, -C(O)alkyl, -C(O)aryl, or -C(O)heteroaryl; R ２ is hydrogen or halogen; A １ is absent, or -O-, -C(O)-, -C(O)-NH-, -C(O)-NH-A ２ａ -, -CH(A ２ａ )-, -N(alkyl)-, -alkyl-; A ２ Or -C(H)(A ２ａ )-, where A ２ａ is hydrogen, alkyl, aryl, heterocycle, or heteroaryl; A ３ is a bond; R ３ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, haloalkyl, heteroaryl, cyano, -C(O)alkyl, -C(O)aryl, or -C(O)heteroaryl; R ４ is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, haloalkyl, heteroaryl, cyano, -C(O)alkyl, -C(O)aryl, -C(O)heteroaryl, or R ５ is linked to form a substituted cycloalkyl; R ５ is hydrogen or R ４ is an alkylene bonded to form said substituted cycloalkyl; Here, R ５ and R ４ When forms said substituted cycloalkyl, said cycloalkyl is substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, alkaryl, aralkyl, haloalkyl, heteroaryl, cyano, -C(O)alkyl, -C(O)aryl, -C(O)heteroaryl, and halogen; R ６ The method of claim 13 or 14, wherein is hydrogen or alkyl.

19. The target protein is FLT3, and Y is 【Chemistry 233】 The method of claim 13 or 14, wherein the compound is selected from the group consisting of:

20. The target protein is B-RAF, and Y is 【Chemical 234】 15. The method of claim 13 or 14, wherein the residue is a compound selected from the group consisting of:

21. The target protein is B-RAF, and Y is 【Chemistry 235】 15. The method of claim 13 or 14, wherein the residue is a compound selected from the group consisting of:

22. The target protein is CDK4 or CDK6, and Y is 【Chemistry 236】 The method of claim 13 or 14, wherein the compound is selected from the group consisting of:

23. the target protein is SHP-2, and Y is 【Chemical 237】 15. The method of claim 13 or 14, wherein the residue is a compound selected from the group consisting of:

24. the target protein is an FGFR1 fusion and / or an FGFR3 fusion, and Y is 【Chemical 238】 The method according to claim 13 or 14, wherein

25. The target protein is MDM2, and Y is 【Chemical 239】 The method according to claim 13 or 14, wherein

26. the target protein is TRIM24, and Y is 【Chemistry 240】 The method according to claim 13 or 14, wherein

27. The target is a SARS-COV2 protein and Y is 【Chemical 241】 The method of claim 13 or 14, wherein the compound is selected from the group consisting of:

28. the target protein is PI3K δ and Y is 【Chemical 242】 The method according to claim 13 or 14, wherein

29. The target protein is MEK and Y is 【Chemical 243】 The method of claim 13 or 14, wherein the compound is selected from the group consisting of:

30. The target protein is BCR-ABL, and Y is 【Chemical 244】 The method of claim 13 or 14, wherein the compound is selected from the group consisting of:

31. The target protein is MLL and Y is 【Chemistry 245】 The method according to claim 13 or 14, wherein

32. The target protein is MALT1, and Y is 【Chemical 246】 The method of claim 13 or 14, wherein the compound is selected from the group consisting of:

33. the target protein is IRAK1, and Y is 【Chemical 247】 The method according to claim 13 or 14, wherein

34. the target protein is one or more kinases, and Y is 【Chemical 248】 The method according to claim 13 or 14, wherein

35. the target protein is one or more kinases, and Y is 【Chemical 249】 The method according to claim 13 or 14, wherein

36. The method of claim 13 or 14, wherein the degron binds to an E3 ubiquitin ligase.

37. The method of claim 13 or 14, wherein the degron binds to cereblon.

38. The degron is 【Chemistry 250】 It is expressed as During the ceremony: Each X １ and X ２ are independently -CH ２ -, -NH, or -C(O)-; Each X ３ , X ４ , X ５ , X ６ , X ７ , or X ８ is independently CH or N; Q is -CH ２ The method according to claim 13 or 14, wherein the alkyl group is -, -O-, -NH-, or -S-.

39. The degron is 【Chemistry 251】 In the formula: W is -CH; Z, 【Chemistry 252】 and L represents a bond to the L linker group or to the Y target binding moiety.

40. The degron is 【Chemistry 253】 It is expressed as W is -CH; Z, 【Chemical 254】 and L represents a bond to the L linker group or to the Y target binding moiety.

41. The method of claim 13 or 14, wherein the L linker group contains 3 to 40 carbon atoms, including one or more acyclic and / or cyclic moieties, wherein one or more carbon atoms may be optionally substituted with a heteroatom selected from O, N, S, and P, or the L linker group comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 ethylene glycol units; wherein the L linker group is optionally substituted.

42. The L linker group: -L １ -L ２ -L ３ -L ４ -L ５ -L ６ -L ７ -, wherein -L １ - is absent, -N(R ２１ )-; C(R ２２ ) -; C １～８ Alkylene; C ２～８ Alkynylene; Q １ or Q ２ and Each -L ２ -, -L ３ -, -L ４ - and -L ５ - is independently absent; -N(R ２１ )-; C(R ２２ )-;-C(O)-;-O-;-(CH ２ -CH ２ -O) １～８ -;C １～８ Alkylene; C ２～８ Alkynylene; Q １ ;Q ２ or Q ３ and Each -L ６ - and -L ７ - is independently absent; -N(R ２１ )-;-C(R ２２ )-;-C(O)-;-C(O)-N(R ２１ ) -; -N(R ２１ )-C(O); or -C(R ２２ )-C(O)-N(R ２１ ) and Each Q １ is a 3- to 7-membered heterocycloalkylene containing at least one nitrogen; Each Q ２ is a 5- to 13-membered spiro bicyclic heterocycloalkylene containing at least one nitrogen; Each Q ３ is a 3- to 6-membered cycloalkylene; R １０ is H or methyl; R １１ The method of claim 13 or 14, wherein is H, methyl, aryl, or heteroaryl.

43. The L linker group is 【255】 【256】 【Chemistry 257】 is selected from the group consisting of 【Chemistry 258】 The method of claim 13 or 14, wherein represents a bond to Y.

44. 15. A compound produced by the method of claim 13 or 14.

45. A pharmaceutical composition comprising a compound according to any one of claims 1 to 12, or a stereoisomer thereof, or a pharma- ceutically acceptable salt thereof, and one or more pharma- ceutically acceptable carriers, excipients, or diluents.

46. A compound according to any one of claims 1 to 12 or a pharmaceutical composition according to claim 45 for use in therapy or diagnosis.

47. A disease or disorder mediated by a target protein in a patient in need thereof, comprising: the target protein is selected from the group consisting of Bruton's tyrosine kinase (BTK); tyrosine-protein kinase (ITK / TSK); bromodomain-containing protein 4 (BRD4); FMS-like tyrosine kinase 3 (FLT-3); Brg / Brahma-associated factor (BAF complex); inducible myeloid leukemia cell differentiation protein (MCL-1); signal transducer and activator of transcription 3 (STAT3); barrier to autointegration factor (BAF); and BCR-ABL; or The target protein is selected from the group consisting of CDK4, CDK6, SHP-2, FGFR, FGFR1 fusion, FGFR3 fusion, MDM2, TRIM24, SARS-COV2, PI3K delta, MEK, BCR-ABL, MLL, MALT1, IRAK1, and kinase; or The disease or disorder is selected from the group consisting of Bruton's tyrosine kinase (BTK), tyrosine-protein kinase (ITK / TSK), bromodomain-containing protein 4 (BRD4), FMS-like tyrosine kinase 3 (FLT-3), Brg / Brahma-associated factor (BAF complex), inducible myeloid leukemia cell differentiation protein (MCL-1), signal transducer and activator of transcription 3 (STAT3), barrier to autointegration factor (BAF), BCR-ABL, CDK4, CDK6, SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2), fibroblast proliferation or mediated by one or more kinases including factor receptor (FGFR), FGFR1 fusion, FGFR3 fusion, mouse double minute 2 homolog (MDM2), tripartite motif containing 24 (TRIM24), SARS-COV2 main protease (Mpro), phosphoinositide 3-kinase (PI3K) delta, mitogen-activated protein kinase kinase (MEK), histone-lysine N-methyltransferase 2A (MLL), mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), interleukin-1 receptor-associated kinase 1 (IRAK1); or The disease or disorder is cancer; optionally the cancer is myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia (CLL), myeloproliferative disorders, myelodysplastic syndromes, small lymphocytic lymphoma (SLL), transformed CLL or Richter's transformation, small cell lymphoma, follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), non-Hodgkin's lymphoma, mantle cell lymphoma (MCL), hepatic leukemia, pulmonary leukemia, pulmonary fibrosis ... selected from the group consisting of marginal zone lymphoma (MZL), Waldenstrom's macroglobulinemia (WM), central nervous system (CNS) lymphoma, metastatic melanoma, head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), platinum-resistant epithelial ovarian cancer (EOC), gastric cancer, metastatic castration-resistant prostate cancer (mCRPC), triple-negative breast cancer (TNBC), muscle-invasive urothelial carcinoma, mesothelioma, cervical cancer, microsatellite-stable colorectal cancer (MSS CRC), and multiple myeloma (MM), Hodgkin's disease, non-Hodgkin's lymphoma (malignant lymphoma) hairy cell, and Waldenstrom's macroglobulinemia; or the disease or disorder is an autoimmune disease; optionally the autoimmune disease is selected from the group consisting of graft-versus-host disease (GVHD), acute graft-versus-host disease, and immune thrombocytopenic purpura (ITP); or The compound of any one of claims 1 to 12 or the pharmaceutical composition of claim 45, wherein the disease or disorder is an inflammatory disease.

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