STAT6 degraders and methods of uses thereof

Abstract

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

Description

WSGR Docket No. 66412-753.601STAT6 DEGRADERS AND METHODS OF USES THEREOFCROSS-REFERENCE

[0001] This application claims the benefit of U. S. Provisional Application Serial No. 63 / 755,933 filed February 7, 2025, U. S. Provisional Application Serial No. 63 / 817,121 filed June 3, 2025, and U. S. Provisional Application Serial No. 63 / 887,096 filed September 24, 2025; which are hereby incorporated by reference in their entirety.BACKGROUND

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

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

[0004] STAT6 is implicated in driving Type 2 immunity, allergies. It may participate in IL-4 / IL-13-mediated allergic reaction, and play a vital role in the differentiation of T-helper type 2 (Th2) cells. STAT6 is a key node primarily activated in the Janus Kinase (JAK) pathway by inflammatory cytokines, interleukin-4 (IL4) and interleukin- 13 (IL 13) and their cognate receptors, which are produced by Th2 cells, mast cells and basophils. Human STAT6 mutations have been associated with severe allergies such as asthma and eczema. There is a need to discover and develop STAT6 drugs, for example to treat allergic / inflammatory diseases and cancers. As such, small molecules that leverage E3 ligase mediated protein degradation to target disease-associated proteins such as STAT6 hold promise as therapeutic agents.SUMMARY

[0005] Disclosed herein is a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:Formula (I) as defined herein.WSGR Docket No. 66412-753.601

[0006] Also disclosed herein is a pharmaceutical composition comprising a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, and a pharmaceutically acceptable excipient.

[0007] Also disclosed herein is a method of treating a disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, or the pharmaceutical composition disclosed herein.

[0008] In some embodiments, the disorder in alopecia, aspergillus, asthma, atomic dermatitis, chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis with nasal polyposis, gastritis, inflammatory bowel disease, pemphigoid, prurigo nodularis, sinusitis, or urticaria.

[0009] Also disclosed herein is a method of degrading STAT6 in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, or the pharmaceutical composition disclosed herein. In some embodiments, the subject has alopecia, aspergillus, asthma, atomic dermatitis, chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis with nasal polyposis, gastritis, inflammatory bowel disease, pemphigoid, prurigo nodularis, sinusitis, or urticaria.INCORPORATION BY REFERENCE

[0010] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.DETAILED DESCRIPTIONDefinitions

[0011] In the following description, certain specific details are set forth to provide a thorough understanding of various embodiments. However, one skilled in the art will understand that the invention may be practiced without these details. In other instances, well-known structures have not been shown or described in detail to avoid unnecessarily obscuring descriptions of the embodiments. Unless the context requires otherwise, throughout the specification and claims which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense, that is, as “including, but not limited to.” Further, headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed invention.

[0012] Reference throughout this specification to “some embodiments” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. Also, as used in this specification and the appendedWSGR Docket No. 66412-753.601claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. It should also be noted that the term “or” is generally employed in its sense including “and / or” unless the content clearly dictates otherwise.

[0013] The terms below, as used herein, have the following meanings, unless indicated otherwise:

[0014] ‘ ‘Oxo” refers to =0.

[0015] ‘ ‘Amino” refers to -NH2.

[0016] “Hydroxy” refers to -OH.

[0017] “Carboxyl” refers to -COOH.

[0018] “Alkyl” refers to a straight-chain or branched-chain saturated hydrocarbon monoradical having from one to about ten carbon atoms, more preferably one to six carbon atoms. Examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2 -methyl- 1 -propyl, 2 -methyl -2 -propyl, 2-methyl-l-butyl, 3 -methyl- 1 -butyl, 2-methyl-3 -butyl, 2,2-dimethyl-l -propyl, 2-methyl-l -pentyl, 3 -methyl- 1 -pentyl, 4-methyl-l -pentyl, 2-methyl-2-pentyl, 3 -methyl -2 -pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-l -butyl, 3,3-dimethyl-1 -butyl, 2 -ethyl- 1 -butyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, tert-amyl and hexyl, and longer alkyl groups, such as heptyl, octyl and the like. Whenever it appears herein, a numerical range, such as “Ci-Ce alkyl,” means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkyl” where no numerical range is designated. In some embodiments, the alkyl is a C1-C10 alkyl. In some embodiments, the alkyl is a Ci-Ce alkyl, a Ci-C5 alkyl, a C1-C4 alkyl, or a C1-C3 alkyl. Unless stated otherwise specifically in the specification, an alkyl group may be optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the alkyl is independently optionally substituted with one or more oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkyl is independently optionally substituted with one or more halogen, -CN, -OH, or -OMe. In some embodiments, the alkyl is independently optionally substituted with halogen.

[0019] “Alkenyl” refers to a straight-chain or branched-chain hydrocarbon monoradical having one or more carbon-carbon double-bonds and having from two to about ten carbon atoms, more preferably two to about six carbon atoms. The group may be in either the cis or trans or Z or E conformation about the double bond(s) and should be understood to include both isomers. Examples include, but are not limited to, ethenyl (-CH=CH2), 1-propenyl (-CH2CH=CH2), isopropenyl [-C(CH3)=CH2], butenyl, 1,3-butadienyl and the like. Whenever it appears herein, a numerical range, such as “C2-C6 alkenyl,” means that the alkenyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkenyl” where no numerical range is designated. Unless stated otherwise specifically in the specification, an alkenyl group may be optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the alkenyl is independently optionally substituted withWSGR Docket No. 66412-753.601one or more oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkenyl is independently optionally substituted with one or more halogen, -CN, -OH, or -OMe. In some embodiments, the alkenyl is independently optionally substituted with halogen.

[0020] “Alkynyl” refers to a straight-chain or branched-chain hydrocarbon monoradical having one or more carbon-carbon triple-bonds and having from two to about ten carbon atoms, more preferably from two to about six carbon atoms. Examples include, but are not limited to, ethynyl, 2-propynyl, 2-butynyl, 1,3-butadiynyl and the like. Whenever it appears herein, a numerical range, such as “C2-C6 alkynyl,” means that the alkynyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms or 6 carbon atoms, although the present definition also covers the occurrence of the term “alkynyl” where no numerical range is designated. Unless stated otherwise specifically in the specification, an alkynyl group may be optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the alkynyl is independently optionally substituted with one or more oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkynyl is independently optionally substituted with one or more halogen, -CN, -OH, or -OMe. In some embodiments, the alkynyl is independently optionally substituted with halogen.

[0021] “Alkylene” refers to a straight or branched divalent hydrocarbon chain. Unless stated otherwise specifically in the specification, an alkylene group may be optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the alkylene is independently optionally substituted with one or more oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkylene is independently optionally substituted with one or more halogen, -CN, -OH, or -OMe. In some embodiments, the alkylene is independently optionally substituted with halogen.

[0022] “Alkoxy” refers to a radical of the formula -Oalkyl where alkyl is defined as above. Unless stated otherwise specifically in the specification, an alkoxy group may be optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the alkoxy is independently optionally substituted with one or more halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkoxy is independently optionally substituted with one or more halogen, -CN, -OH, or -OMe. In some embodiments, the alkoxy is independently optionally substituted with halogen.

[0023] “Aryl” refers to a radical derived from a hydrocarbon ring system comprising 6 to 30 carbon atoms and at least one aromatic ring. The aryl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with a cycloalkyl or heterocycloalkyl ring, the aryl is bonded through an aromatic ring atom) or bridged ring systems. In some embodiments, the aryl is a 6- to 10-membered aryl. In some embodiments, the aryl is a 6-membered aryl (phenyl). Aryl radicals include, but are not limited to, anthracenyl, naphthyl, phenanthrenyl, azulenyl, phenyl, chrysenyl,WSGR Docket No. 66412-753.601fluoranthenyl, fluorenyl, as-indacenyl, s-indacenyl, indanyl, indenyl, phenalenyl, phenanthrenyl, pleiadenyl, pyrenyl, and triphenylenyl. Unless stated otherwise specifically in the specification, an aryl may be optionally substituted, for example, with one or more halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the aryl is independently optionally substituted with one or more halogen, methyl, ethyl, -CN, -COOH, -COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the aryl is independently optionally substituted with one or more halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the aryl is independently optionally substituted with halogen.

[0024] “Cycloalkyl” refers to a partially or fully saturated, monocyclic, or polycyclic carbocyclic ring, which may include fused (when fused with an aryl or a heteroaryl ring, the cycloalkyl is bonded through a non-aromatic ring atom), spiro, and / or bridged ring systems. In some embodiments, the cycloalkyl is fully saturated. Representative cycloalkyls include, but are not limited to, cycloalkyls having from three to fifteen carbon atoms (e.g., C3-C15 fully saturated cycloalkyl or C3-C15 cycloalkenyl), from three to ten carbon atoms (e.g., C3-C10 fully saturated cycloalkyl or C3-C10 cycloalkenyl), from three to eight carbon atoms (e.g., C3-C8 fully saturated cycloalkyl or C3-C8 cycloalkenyl), from three to six carbon atoms (e.g., C3-C6 fully saturated cycloalkyl or C3-C6 cycloalkenyl), from three to five carbon atoms (e.g., C3-C5 fully saturated cycloalkyl or C3-C5 cycloalkenyl), or three to four carbon atoms (e.g., C3-C4 fully saturated cycloalkyl or C3-C4 cycloalkenyl). In some embodiments, the cycloalkyl is a 3 - to 10-membered fully saturated cycloalkyl or a 3- to 10-membered cycloalkenyl. In some embodiments, the cycloalkyl is a 3- to 6-membered fully saturated cycloalkyl or a 3 - to 6-membered cycloalkenyl. In some embodiments, the cycloalkyl is a 5 - to 6-membered fully saturated cycloalkyl or a 5- to 6-membered cycloalkenyl.Monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyls include, for example, adamantyl, norbomyl, decalinyl, bicyclo[3.3.0]octyl, bicyclo[4.3.0]nonyl, cis-decalinyl, trans-decalinyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[3.2.1]octyl, bicyclo[3.2.2]nonyl, and bicyclo[3.3.2]decyl, bicyclo [1.1. l]pentyl, bicyclo[3.1.0]hexyl, bicyclo[3.1.1]heptyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, spiro[4.2]heptyl, spiro[4.3]octyl, spiro [5.2] octyl, spiro[3.3]heptyl, and spiro [5.3] nonyl. Partially saturated cycloalkyls include, for example cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Unless stated otherwise specifically in the specification, a cycloalkyl is independently optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, a cycloalkyl is independently optionally substituted with one or more oxo, halogen, methyl, ethyl, -CN, -COOH, -COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, a cycloalkyl is independently optionally substituted with one or more oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the cycloalkyl is independently optionally substituted with halogen.WSGR Docket No. 66412-753.601

[0025] “Halo” or “halogen” refers to bromo, chloro, fluoro or iodo. In some embodiments, halogen is fluoro or chloro. In some embodiments, halogen is fluoro. In some embodiments, halogen is chloro.

[0026] “Haloalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more halo radicals, as defined above, e.g., trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1,2-difluoroethyl, 2-fluoroethyl, 3 -bromo-2 -fluoropropyl, 1,2-dibromoethyl, and the like.

[0027] “Haloalkoxy” refers to -O-haloalkyl, with haloalkyl as defined above.

[0028] “Hydroxyalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more hydroxyls. In some embodiments, the alkyl is substituted with one hydroxyl. In some embodiments, the alkyl is substituted with one, two, or three hydroxyls. Hydroxyalkyl includes, for example, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, or hydroxypentyl. In some embodiments, the hydroxyalkyl is hydroxymethyl.

[0029] “Aminoalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more amines. In some embodiments, the alkyl is substituted with one amine. In some embodiments, the alkyl is substituted with one, two, or three amines. Aminoalkyl includes, for example, aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the aminoalkyl is aminomethyl.

[0030] “Heteroalkyl” refers to an alkyl group in which one or more skeletal atoms of the alkyl are selected from an atom other than carbon, e.g., oxygen, nitrogen, sulfur, phosphorus, or combinations thereof. A heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl. In one aspect, a heteroalkyl is a Ci-Ce heteroalkyl wherein the heteroalkyl is comprised of 1 to 6 carbon atoms and one or more atoms other than carbon, e.g., oxygen, nitrogen, sulfur, phosphorus, or combinations thereof wherein the heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl. In one aspect, a heteroalkyl is a Ci-Ce heteroalkyl wherein the heteroalkyl is comprised of 1 to 6 carbon atoms and one or two atoms selected from the group consisting of oxygen, nitrogen, and sulfur wherein the heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl. Examples of such heteroalkyl are, for example, -CH2OCH3, -CH2CH2OCH3, -CH2CH2OCH2CH2OCH3, -CH(CH3)OCH3, -CH2NHCH3, -CH2N(CH3)2, -CH2CH2NHCH3, or -CH2CH2N(CH3)2. Unless stated otherwise specifically in the specification, a heteroalkyl is independently optionally substituted for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, a heteroalkyl is independently optionally substituted with one or more oxo, halogen, methyl, ethyl, -CN, -CF3, OH, -OMe, NH2, or -NO2. In some embodiments, a heteroalkyl is independently optionally substituted with one or more oxo, halogen, methyl, ethyl, -CN, -CF3, OH, or -OMe. In some embodiments, the heteroalkyl is independently optionally substituted with halogen.

[0031] “Heterocycloalkyl” refers to a 3- to 24-membered partially or fully saturated ring radical comprising 2 to 23 carbon atoms and from one to 8 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorous, silicon, and sulfur. In some embodiments, the heterocycloalkyl is a 3- to 8-membered partially or fully saturated ring comprising one, two, or three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heterocycloalkyl is a 3 - to 6-WSGR Docket No. 66412-753.601membered partially or fully saturated ring comprising one or two heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heterocycloalkyl is a 3 - to 6-membered fully saturated ring comprising one or two heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heterocycloalkyl is fully saturated. In some embodiments, the heterocycloalkyl is C-linked. In some embodiments, the heterocycloalkyl is N-linked. In some embodiments, the heterocycloalkyl comprises one to three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heterocycloalkyl comprises one to three heteroatoms selected from the group consisting of nitrogen and oxygen. In some embodiments, the heterocycloalkyl comprises one to three nitrogens. In some embodiments, the heterocycloalkyl comprises one or two nitrogens. In some embodiments, the heterocycloalkyl comprises one nitrogen. In some embodiments, the heterocycloalkyl comprises one nitrogen and one oxygen. Unless stated otherwise specifically in the specification, the heterocycloalkyl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with an aryl or a heteroaryl ring, the heterocycloalkyl is bonded through a non-aromatic ring atom), spiro, or bridged ring systems; and the nitrogen, carbon, or sulfur atoms in the heterocycloalkyl radical may be optionally oxidized; the nitrogen atom may be optionally quatemized. Representative heterocycloalkyls include, but are not limited to, heterocycloalkyls having from two to fifteen carbon atoms (e.g., C2-C15 fully saturated heterocycloalkyl or C2-C15 heterocycloalkenyl), from two to ten carbon atoms (e.g., C2-C10 fully saturated heterocycloalkyl or C2-C10 heterocycloalkenyl), from two to eight carbon atoms (e.g., C2-C8 fully saturated heterocycloalkyl or C2-C8 heterocycloalkenyl), from two to seven carbon atoms (e.g., C2-C7 fully saturated heterocycloalkyl or C2-C7 heterocycloalkenyl), from two to six carbon atoms (e.g., C2-C6 fully saturated heterocycloalkyl or C2-C7 heterocycloalkenyl), from two to five carbon atoms (e.g., C2-C5 fully saturated heterocycloalkyl or C2-C5 heterocycloalkenyl), or two to four carbon atoms (e.g., C2-C4 fully saturated heterocycloalkyl or C2-C4 heterocycloalkenyl). Examples of such heterocycloalkyl radicals include, but are not limited to, aziridinyl, azetidinyl, oxetanyl, dioxolanyl, thienyl[l,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1 -oxo-thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, 1,3-dihydroisobenzofuran-l-yl, 3-oxo-l,3-dihydroisobenzofuran-l-yl, methyl-2-oxo-l,3-dioxol-4-yl, and 2-oxo-l,3-dioxol-4-yl. The term heterocycloalkyl also includes all ring forms of the carbohydrates, including but not limited to the monosaccharides, the disaccharides, and the oligosaccharides. In some embodiments, heterocycloalkyls have from 2 to 10 carbons in the ring. It is understood that when referring to the number of carbon atoms in a heterocycloalkyl, the number of carbon atoms in the heterocycloalkyl is not the same as the total number of atoms (including the heteroatoms) that make up the heterocycloalkyl (i.e., skeletal atoms of the heterocycloalkyl ring). In some embodiments, the heterocycloalkyl is a 3- to 8-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 3 - to 7-membered heterocycloalkyl. InWSGR Docket No. 66412-753.601some embodiments, the heterocycloalkyl is a 3- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 4- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 5- to 6-membered heterocycloalkyl. In some embodiments, the heterocycloalkyl is a 3- to 8-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 3 - to 7-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 3 - to 6-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 4- to 6-membered heterocycloalkenyl. In some embodiments, the heterocycloalkyl is a 5 - to 6-membered heterocycloalkenyl. Unless stated otherwise specifically in the specification, a heterocycloalkyl is independently optionally substituted, for example, with one or more oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, and the like. In some embodiments, the heterocycloalkyl is independently optionally substituted with one or more oxo, halogen, methyl, ethyl, -CN, -COOH, -COOMe, -CFs, -OH, -OMe, -NH2, or -NO2. In some embodiments, the heterocycloalkyl is independently optionally substituted with one or more halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heterocycloalkyl is independently optionally substituted with halogen.

[0032] “Heteroaryl” refers to a 5 - to 14-membered ring system radical comprising one to thirteen carbon atoms, one to six heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorous, and sulfur, and at least one aromatic ring. In some embodiments, the heteroaryl is a 5 - to 10-membered ring comprising one, two, or three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heteroaryl is a 5 - to 6-membered ring comprising one or two heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heteroaryl comprises one to three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heteroaryl comprises one to three heteroatoms selected from the group consisting of nitrogen and oxygen. In some embodiments, the heteroaryl comprises one to three nitrogens. In some embodiments, the heteroaryl comprises one or two nitrogens. In some embodiments, the heteroaryl comprises one nitrogen. In some embodiments, the heteroaryl is C-linked. In some embodiments, the heteroaryl is N-linked. The heteroaryl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with a cycloalkyl or heterocycloalkyl ring, the heteroaryl is bonded through an aromatic ring atom) or bridged ring systems; and the nitrogen, carbon, or sulfur atoms in the heteroaryl radical may be optionally oxidized; the nitrogen atom may be optionally quatemized. In some embodiments, the heteroaryl is a 5 - to 10-membered heteroaryl comprising 1, 2, or 3 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. In some embodiments, the heteroaryl is a 5 - to 6-membered heteroaryl comprising 1, 2, or 3 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. In some embodiments, the heteroaryl is a 6-membered heteroaryl comprising 1, 2, or 3 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. In some embodiments, the heteroaryl is a 5 -membered heteroaryl comprising 1, 2, or 3 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. Examples include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl,WSGR Docket No. 66412-753.601benzindolyl, benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiadiazolyl, benzo[b][l,4]dioxepinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[l,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, isothiazolyl, imidazolyl, indazolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, 1 -oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl, 1-oxidopyridazinyl, 1 -phenyl- IH-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e., thienyl). Unless stated otherwise specifically in the specification, a heteroaryl is independently optionally substituted, for example, with one or more halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocycloalkyl, or heteroaryl, and the like. In some embodiments, the heteroaryl is independently optionally substituted with one or more halogen, methyl, ethyl, -CN, -COOH, -COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the heteroaryl is independently optionally substituted with one or more halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heteroaryl is independently optionally substituted with halogen.

[0033] The term “optional” or “optionally” means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances in which it does not. For example, “optionally substituted alkyl” means either “alkyl” or “substituted alkyl” as defined above. Further, an optionally substituted group may be unsubstituted (e.g., -CH2CH3), fully substituted (e.g., -CF2CF3), mono-substituted (e.g., -CH2CH2F) or substituted at a level anywhere in-between fully substituted and mono-substituted (e.g., -CH2CHF2, -CH2CF3, -CF2CH3, -CFHCHF2, etc ).

[0034] The term “one or more” when referring to an optional substituent means that the subject group is independently optionally substituted with one, two, three, or four, or more substituents. In some embodiments, the subject group is independently optionally substituted with one, two, three, or four substituents. In some embodiments, the subject group is independently optionally substituted with one, two, or three substituents. In some embodiments, the subject group is independently optionally substituted with one or two substituents. In some embodiments, the subject group is independently optionally substituted with one substituent. In some embodiments, the subject group is independently optionally substituted with two substituents. In some embodiments, the subject group is independently optionally substituted with three substituents.

[0035] An “effective amount” or “therapeutically effective amount” refers to an amount of a compound administered to a mammalian subject, either as a single dose or as part of a series of doses, which is effective to produce a desired therapeutic effect.

[0036] ‘ ‘Treatment” of an individual (e.g., a mammal, such as a human) or a cell is any type of intervention used in an attempt to alter the natural course of the individual or cell. In some embodiments,WSGR Docket No. 66412-753.601treatment includes administration of a pharmaceutical composition subsequent to the initiation of a pathologic event or contact with an etiologic agent and includes stabilization of the condition (e.g., condition does not worsen) or alleviation of the condition.

[0037] “Synergy” or “synergize” refers to an effect of a combination that is greater than additive of the effects of each component alone at the same doses.

[0038] As used herein, a “disease or disorder associated with STAT6” or, alternatively, “a STAT6-mediated disease or disorder” means any disease or other deleterious condition in which STAT6, or a mutant thereof, is known or suspected to play a role.Compounds

[0039] Described herein are compounds, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, useful in the treatment of a disease or disorder associated with STAT6.

[0040] Disclosed herein is a compound of Formula (I), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:Formula (I);wherein:R30is hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, or -L- heterocycloalkyl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”;R31is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R”;X is -O-, -S-, -NR32-, or -C(R33)2-;R32is hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, or -L- heterocycloalkyl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substitutedWSGR Docket No. 66412-753.601with one or more R’ and wherein each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”;each R33is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, Ci- Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”;each Z is independently N or CR2;each R2is independently hydrogen, halogen, -CN, or Ci-Cealkyl independently optionally substituted with one or more R’;- is a single or a double bond;U is N or C;T is N or C; provided that U and T are not both N;Y1is N, C, or CR3;R3is hydrogen, halogen, -CN, or Ci-Cealkyl independently optionally substituted with one or more R’; Y2is N, NRY2, CR4, C(R4)2, or C(=O);each R4is independently hydrogen, halogen, -CN, or Ci-Cealkyl independently optionally substituted with one or more R’;RY2is hydrogen or Ci-Cealkyl independently optionally substituted with one or more R;Y3is N or C;X1is N or CR5;R5is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, or Ci-Cealkyl independently optionally substituted with one or more R’;X2is N or CR6;R6is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, or Ci-Cealkyl independently optionally substituted with one or more R’;X3is N or CR7;R7is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, or Ci-Cealkyl is independently optionally substituted with one or more R’;Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;each R8is independently halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, Ci- Cealkyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”; and / or two R8on the same atom are taken together to form an oxo;m is 0, 1, 2, 3, or 4;each L1is independently -O-, -S-, -S(=O)-, -S(=O)2-, -NR9-, -C(=O)-, Ci-Cioalkylene, Ci- Cioheteroalkylene, C2-Cealkenylene, C2-Cealkynylene, cycloalkylene, heterocycloalkylene, arylene,WSGR Docket No. 66412-753.601or heteroarylene; wherein each alkylene, alkenylene, alkynylene, and heteroalkylene is independently optionally substituted with one or more R’ and wherein each cycloalkylene, heterocycloalkylene, arylene, and heteroarylene is independently optionally substituted with one or more R”;each R9is independently hydrogen or Ci-Cealkyl independently optionally substituted with one or more R’;s is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;| — M’ is an E3 ubiquitin ligase targeting agent;each Rais independently Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, -L- heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”;each Rbis independently hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L- cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”; each Rcand Rdare independently hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, - L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl independently optionally substituted with one or more R”;L is absent or Ci-Csalkylene optionally substituted with one or more R’; andeach R’ is independently halogen, -CN, -OH, -OCi-Csalkyl, -S(=O)Ci-C3alkyl, -S(=O)2Ci-C3alkyl, -S(=O)2NH2, -S(=O)2NHCi-C3alkyl, -S(=O)2N(Ci-C3alkyl)2, -NH2, -NHCi-C3alkyl, -N(Ci-C3alkyl)2, - NHC(=O)OCi-C3alkyl, -C(=O)Ci-C3alkyl, -C(=O)OH, -C(=O)OCi-C3alkyl, -C(=O)NH2, - C(=O)N(Ci-C3alkyl)2, or -C(=O)NHCi-C3alkyl; wherein each alkyl is independently optionally substituted with one or more halogen;and / or two R’ on the same atom are taken together to form an oxo; andeach R” is independently halogen, -CN, -OH, -OCi-Csalkyl, -S(=O)Ci-C3alkyl, -S(=O)2Ci-C3alkyl, -S(=O)2NH2, -S(=O)2NHCi-C3alkyl, -S(=O)2N(Ci-C3alkyl)2, -NH2, -NHCi-C3alkyl, -N(Ci-C3alkyl)2, - NHC(=O)OCi-C3alkyl, -C(=O)Ci-C3alkyl, -C(=O)OH, -C(=O)OCi-C3alkyl, -C(=O)NH2, - C(=O)N(Ci-C3alkyl)2, -C(=O)NHCi-C3alkyl, Ci-C3alkyl, Ci-C3heteroalkyl, Ci-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more halogen;and / or two R” on the same atom are taken together to form an oxo.

[0041] Disclosed herein is a compound of formula (I), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:WSGR Docket No. 66412-753.601Formula (I);wherein:R30is hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, or -L- heterocycloalkyl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”;R31is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R”;X is -O-, -S-, -NR32-, or -C(R33)2-;R32is hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, or -L- heterocycloalkyl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”;each R33is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, Ci- Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”;each Z is independently N or CR2;each R2is independently hydrogen, halogen, -CN, or Ci-Cealkyl independently optionally substituted with one or more R’;- is a single or a double bond;U is N or C;T is N or C; provided that U and T are not both N;Y1is N, C, or CR3;R3is hydrogen, halogen, -CN, or Ci-Cealkyl independently optionally substituted with one or more R’;WSGR Docket No. 66412-753.601Y2is N, NRY2, CR4, C(R4)2, or C(=O);each R4is independently hydrogen, halogen, -CN, or Ci-Cealkyl independently optionally substituted with one or more R’;RY2is hydrogen or Ci-Cealkyl independently optionally substituted with one or more R;Y3is N or C;X1is N or CR5;R5is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, or Ci-Cealkyl independently optionally substituted with one or more R’;X2is N or CR6;R6is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, or Ci-Cealkyl independently optionally substituted with one or more R’;X3is N or CR7;R7is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, or Ci-Cealkyl is independently optionally substituted with one or more R’;Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;each R8is independently halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, Ci- Cealkyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”; and / or two R8on the same atom are taken together to form an oxo;m is 0, 1, 2, 3, or 4;each L1is independently -O-, -S-, -S(=O)-, -S(=O)2-, -NR9-, -C(=O)-, Ci-Cioalkylene, Ci- Cioheteroalkylene, C2-Cealkenylene, C2-Cealkynylene, cycloalkylene, heterocycloalkylene, arylene, or heteroarylene; wherein each alkylene, alkenylene, alkynylene, and heteroalkylene is independently optionally substituted with one or more R’ and wherein each cycloalkylene, heterocycloalkylene, arylene, and heteroarylene is independently optionally substituted with one or more R”;each R9is independently hydrogen or Ci-Cealkyl independently optionally substituted with one or more R’;s is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;I — M’ is an E3 ubiquitin ligase targeting agent;each Rais independently Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, -L- heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”;each Rbis independently hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L- cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”;WSGR Docket No. 66412-753.601each Rcand Rdare independently hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, - L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl independently optionally substituted with one or more R”;L is absent or Ci-Csalkylene optionally substituted with one or more R’; andeach R’ is independently halogen, -CN, -OH, -OCi-Csalkyl, -S(=O)Ci-C3alkyl, -S(=O)2Ci-C3alkyl, -S(=O)2NH2, -S(=O)2NHCi-C3alkyl, -S(=O)2N(Ci-C3alkyl)2, -NH2, -NHCi-C3alkyl, -N(Ci-C3alkyl)2, - NHC(=O)OCi-C3alkyl, -C(=O)Ci-C3alkyl, -C(=O)OH, -C(=O)OCi-C3alkyl, -C(=O)NH2, - C(=O)N(Ci-C3alkyl)2, or -C(=O)NHCi-C3alkyl; wherein each alkyl is independently optionally substituted with one or more halogen;and / or two R’ on the same atom are taken together to form an oxo; andeach R” is independently halogen, -CN, -OH, -OCi-Csalkyl, -S(=O)Ci-C3alkyl, -S(=O)2Ci-C3alkyl, -S(=O)2NH2, -S(=O)2NHCi-C3alkyl, -S(=O)2N(Ci-C3alkyl)2, -NH2, -NHCi-C3alkyl, -N(Ci-C3alkyl)2, - NHC(=O)OCi-C3alkyl, -C(=O)Ci-C3alkyl, -C(=O)OH, -C(=O)OCi-C3alkyl, -C(=O)NH2, - C(=O)N(Ci-C3alkyl)2, -C(=O)NHCi-C3alkyl, Ci-C3alkyl, Ci-C3heteroalkyl, Ci-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more halogen;and / or two R” on the same atom are taken together to form an oxo.

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

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

[0044] In some embodiments of a compound of Formula (I), Y2is N. In some embodiments of a compound of Formula (I), Y2is NRY2. In some embodiments of a compound of Formula (I), Y2is CR4. In some embodiments of a compound of Formula (I), Y2is C(R4)2. In some embodiments of a compound of Formula (I), Y2is C(=O).

[0045] In some embodiments of a compound of Formula (I), Y3is N. In some embodiments of a compound of Formula (I), Y3is C.

[0046] In some embodiments of a compound of Formula (I), X1is N. In some embodiments of a compound of Formula (I), X1is CR5.

[0047] In some embodiments of a compound of Formula (I), X2is N. In some embodiments of a compound of Formula (I), X2is CR6.

[0048] In some embodiments of a compound of Formula (I), X3is N. In some embodiments of a compound of Formula (I), X3is CR7.WSGR Docket No. 66412-753.601

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

[0050] In some embodiments of a compound of Formula (I), N or CR3; and Y2is NRY2, C(R4)2, or C(=O).

[0051] In some embodiments of a compound of Formula (I),within the 6-membered ring containing U, T, X1, X2, and X3means that the 6-membered ring is aromatic.

[0052] In some embodiments of a compound of Formula (I),within the 5-membered ring containing U, T, Y1, Y2, and Y3means that the 5 -membered ring is aromatic, partially saturated, or fully saturated.

[0053] In some embodiments of a compound of Formula (I),within the 5-membered ring containing U, T, Y1, Y2, and Y3means that the 5-membered ring is aromatic.

[0054] In some embodiments of a compound of Formula (I),within the 5-membered ring containing U, T, Y1, Y2, and Y3means that the 5-membered ring is partially saturated or fully saturated.R6WSGR Docket No. 66412-753.601

[0058] In some embodiments of a compound of Formula (I), some embodiments of a compound of Formula (I), or O

[0059] In some embodiments of a compound of Formula (I), some embodiments of a compound of Formula (I), or O

[0060] In some embodiments of a compound of Formula (I),

[0061] In some embodiments of a compound of Formula (I), some embodiments of a compound of Formula (I), o

[0062] In some embodiments of a compound of Formula (I),WSGR Docket No. 66412-753.601

[0063] In some embodiments of a compound of Formula (I),R7

[0064] In some embodiments of a compound of Formula (I),

[0066] In some embodiments of a compound of Formula (I),

[0067] In some embodiments of a compound of Formula (I),

[0068] In some embodiments of a compound of Formula (I),WSGR Docket No. 66412-753.601R5x-XR6

[0069] In some embodiments of a compound of Formula (I), is R7R5R6, or R6R30HN-,N—I

[0070] In some embodiments of a compound of Formula (I), R20is " N in some embodiments R30h NA. Iof a compound of Formula (I), R20is R31. In some embodiments of a compound of Formula (I), R30 / ?R20is R31

[0071] In some embodiments of a compound of Formula (I), X is -O-.

[0072] In some embodiments of a compound of Formula (I), R30is hydrogen, Ci-Cealkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (I), R30is Ci-Cealkyl.

[0073] In some embodiments of a compound of Formula (I), R31is hydrogen, halogen, -CN, Ci-Cealkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more R’. In some embodiments of a compound of Formula (I), R31is Ci-Cealkyl.O

[0074] In some embodiments of a compound of Formula (I), R20is

[0075] In some embodiments of a compound of Formula (I), each Z is independently CR2. In some embodiments of a compound of Formula (I), one Z is N and the remaining Z are independently CR2.R2

[0076] In some embodiments of a compound of Formula (I), H Z~ ZH is\= / insome R2embodiments of a compound of Formula (I),Z Z is \= /

[0077] In some embodiments of a compound of Formula (I), each R2is independently hydrogen, halogen, or Ci-Cealkyl independently optionally substituted with one or more R’. In some embodiments of a compound of Formula (I), each R2is independently hydrogen, halogen, or Ci-Cealkyl. In some embodiments of a compound of Formula (I), each R2is independently hydrogen or Ci-Cealkyl. In someWSGR Docket No. 66412-753.601embodiments of a compound of Formula (I), each R2is independently hydrogen or halogen. In some embodiments of a compound of Formula (I), each R2is independently hydrogen.

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

[0079] In some embodiments of a compound of Formula (I),is. In someembodiments of a compound of Formula (I),is

[0080] In some embodiments of a compound of Formula (I), the compound is of Formula (la):(R8)mO.N NFormula (la).

[0081] In some embodiments of a compound of Formula (I), the compound is of Formula (lb):(R8)mM-(L1) 'SsoO.NR6Formula (lb).

[0082] In some embodiments of a compound of Formula (I), the compound is of Formula (Ic):(R8)m'sO.NOFormula (Ic).

[0083] In some embodiments of a compound of Formula (I), the compound is of Formula (Id):WSGR Docket No. 66412-753.601

[0084] In some embodiments of a compound of Formula (Id), Y1is N. In some embodiments of a compound of Formula (Id), Y1is CH.

[0085] In some embodiments of a compound of Formula (la)-(Id), X3is N. In some embodiments of a compound of Formula (la)-(Id), X3is CR7.

[0086] In some embodiments of a compound of Formula (I), R3is hydrogen or Ci-Cealkyl. In some embodiments of a compound of Formula (I), R3is hydrogen.

[0087] In some embodiments of a compound of Formula (I) or (la), each R4is independently hydrogen, halogen, or Ci-Cealkyl. In some embodiments of a compound of Formula (I) or (la), each R4is independently hydrogen.

[0088] In some embodiments of a compound of Formula (I), RY2is hydrogen or Ci-Cealkyl. In some embodiments of a compound of Formula (I), R5is hydrogen, halogen, or Ci-Cealkyl independently optionally substituted with one or more R’. In some embodiments of a compound of Formula, R5is hydrogen or Ci-Cealkyl. In some embodiments of a compound of Formula (I), R5is hydrogen.

[0089] In some embodiments of a compound of Formula (I) or (la)-(Id), R6is hydrogen, halogen, or Ci-Cealkyl independently optionally substituted with one or more R’. In some embodiments of a compound of Formula (I) or (la)-(Id), R6is hydrogen or Ci-Cealkyl. In some embodiments of a compound of Formula (I) or (la)-(Id), R6is hydrogen. In some embodiments of a compound of Formula (I) or (la)-(Id), R6is Ci-Cealkyl. In some embodiments of a compound of Formula (I) or (la)-(Id), R6is Ci-Cealkyl or Ci-Cehaloalkyl.

[0090] In some embodiments of a compound of Formula (I) or (la)-(Id), R7is hydrogen, halogen, or Ci-Cealkyl is independently optionally substituted with one or more R’. In some embodiments of a compound of Formula (I) or (la)-(Id), R7is hydrogen or Ci-Cealkyl. In some embodiments of a compound of Formula (I) or (la)-(Id), R7is hydrogen. In some embodiments of a compound of Formula (I) or (la)-(Id), R7is Ci-C6alkyl.

[0091] In some embodiments of a compound of Formula (I) or (la)-(Id), Ring A is aryl or heteroaryl. In some embodiments of a compound of Formula (I) or (la)-(Id), Ring A is phenyl or 5- or 6-membered heteroaryl. In some embodiments of a compound of Formula (I) or (la)-(Id), Ring A is phenyl. In some embodiments of a compound of Formula (I) or (la)-(Id), Ring A is 6-membered heteroaryl. In some embodiments of a compound of Formula (I) or (la)-(Id), Ring A is pyridinyl, pyrimidinyl, or pyrazinyl. In some embodiments of a compound of Formula (I) or (la)-(Id), Ring A is pyridinyl. In someWSGR Docket No. 66412-753.601embodiments of a compound of Formula (I) or (la)-(Id), Ring A is 5-membered heteroaryl. In some embodiments of a compound of Formula (I) or (la)-(Id), Ring A is phenyl or pyridinyl.

[0092] In some embodiments of a compound of Formula (I) or (la)-(Id), each R8is independently halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)NRcRd, or Ci-Cealkyl independently optionally substituted with one or more R’. In some embodiments of a compound of Formula (I) or (la)-(Id), each R8is independently halogen, -CN, -ORa, -C(=O)NRcRd, or Ci-Cealkyl. In some embodiments of a compound of Formula (I) or (la)-(Id), each R8is independently halogen, -C(=O)NRcRd, or Ci-Cealkyl. In some embodiments of a compound of Formula (I) or (la)-(Id), each R8is independently halogen or Ci-Cealkyl. In some embodiments of a compound of Formula (I) or (la)-(Id), each R8is independently -C(=O)NRcRd. In some embodiments of a compound of Formula (I) or (la)-(Id), each R8is independently halogen or -C(=O)NRcRd. In some embodiments of a compound of Formula (I) or (la)-(Id), each R8is independently halogen or -C(=O)NH(heteroaryl) wherein the heteroaryl is independently optionally substituted with one or more R”. In some embodiments of a compound of Formula (I) or (la)-(Id), each R8is independently -C(=O)NH(heteroaryl) wherein the heteroaryl is independently optionally substituted with one or more R”

[0093] In some embodiments of a compound of Formula (I) or (la) -(Id), m is 1, 2, or 3. In some embodiments of a compound of Formula (I) or (la)-(Id), m is 1 or 2. In some embodiments of a compound of Formula (I) or (la)-(Id), m is 0. In some embodiments of a compound of Formula (I) or (la)-(Id), m is 1. In some embodiments of a compound of Formula (I) or (la) -(Id), m is 2.(R8)m

[0094] In some embodiments of a compound of Formula (I) or (la)-(Id),O z \( CH, wherein:Ring C is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;each R” is independently halogen, -CN, -OH, -OCi-Csalkyl, -S(=O)Ci-C3alkyl, -S(=O)2Ci-C3alkyl, -S(=O)2NH2, -S(=O)2NHCi-C3alkyl, -S(=O)2N(Ci-C3alkyl)2, -NH2, -NHCi-C3alkyl, -N(Ci-C3alkyl)2, - NHC(=O)OCi-C3alkyl, -C(=O)Ci-C3alkyl, -C(=O)OH, -C(=O)OCi-C3alkyl, -C(=O)NH2, - C(=O)N(Ci-C3alkyl)2, -C(=O)NHCi-C3alkyl, Ci-C3alkyl, Ci-C3heteroalkyl, Ci-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more halogen;and / or two R” on the same atom are taken together to form an oxo; andu is 0, 1, 2, 3, or 4.WSGR Docket No. 66412-753.601

[0095] In some embodiments of a compound of Formula (I) or (la)-(Id),(R")u, wherein:Ring C is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;R8ais hydrogen, halogen, -CN, Ci-Cealkyl, or Ci-Cehaloalkyl;each R” is independently halogen, -CN, -OH, -OCi-Csalkyl, -S(=O)Ci-C3alkyl, -S(=O)2Ci-C3alkyl, -S(=O)2NH2, -S(=O)2NHCi-C3alkyl, -S(=O)2N(Ci-C3alkyl)2, -NH2, -NHCi-C3alkyl, -N(Ci-C3alkyl)2, - NHC(=O)OCi-C3alkyl, -C(=O)Ci-C3alkyl, -C(=O)OH, -C(=O)OCi-C3alkyl, -C(=O)NH2, - C(=O)N(Ci-C3alkyl)2, -C(=O)NHCi-C3alkyl, Ci-C3alkyl, Ci-C3heteroalkyl, Ci-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more halogen;and / or two R” on the same atom are taken together to form an oxo; andu is 0, 1, 2, 3, or 4.Ring C is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;R8ais hydrogen, halogen, -CN, Ci-Cealkyl, or Ci-Cehaloalkyl;WSGR Docket No. 66412-753.601each R” is independently halogen, -CN, -OH, -OCi-Csalkyl, -S(=O)Ci-C3alkyl, -S(=O)2Ci-C3alkyl, -S(=O)2NH2, -S(=O)2NHCi-C3alkyl, -S(=O)2N(Ci-C3alkyl)2, -NH2, -NHCi-C3alkyl, -N(Ci-C3alkyl)2, - NHC(=O)OCi-C3alkyl, -C(=O)Ci-C3alkyl, -C(=O)OH, -C(=O)OCi-C3alkyl, -C(=O)NH2, - C(=O)N(Ci-C3alkyl)2, -C(=O)NHCi-C3alkyl, Ci-C3alkyl, Ci-C3heteroalkyl, Ci-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more halogen;and / or two R” on the same atom are taken together to form an oxo; andu is 0, 1, 2, 3, or 4.

[0099] In some embodiments, Ring C is a heteroaryl. In some embodiments, Ring C is a 5 -membered heteroaryl. In some embodiments, Ring C is a 5 -membered heteroaryl comprising one or two heteroatoms selected from the group consisting of N, O, and S. In some embodiments, Ring C is a 5-membered heteroaryl comprising one or two heteroatoms selected from the group consisting ofN and O. In some embodiments, Ring C is a 5-membered heteroaryl comprising one or two heteroatoms that are N.

[0100] In some embodiments, u is 0, 1, or 2. In some embodiments, u is 1 or 2. In some embodiments, u is 0. In some embodiments, u is 1. In some embodiments, u is 2.

[0101] In some embodiments, R8ais hydrogen, halogen, or Ci-Cealkyl. In some embodiments, R8ais hydrogen or halogen. In some embodiments, R8ais hydrogen, halogen, or Ci-Cealkyl. In some embodiments, R8ais hydrogen. In some embodiments, R8ais hydrogen, halogen, or Ci-Cealkyl. In some embodiments, R8ais halogen, -CN, Ci-Cealkyl, or Ci-Cehaloalkyl. In some embodiments, R8ais halogen, Ci-Cealkyl, or Ci-Cehaloalkyl. In some embodiments, R8ais halogen or Ci-Cealkyl. In some embodiments, R8ais halogen.WSGR Docket No. 66412-753.601

[0103] In some embodiments of a compound of Formula (I) or (la)-(Id),

[0104] In some embodiments of a compound of Formula (I) or (la)-(Id),

[0105] In some embodiments of a compound of Formula (I) or (la)-(Id),

[0106] In some embodiments of a compound of Formula (I) or (la)-(Id),

[0107] Also disclosed herein is a compound of Formula (II), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:WSGR Docket No. 66412-753.601Formula (II);wherein:R30is hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, or -L- heterocycloalkyl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”;R31is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R”;X is -O-, -S-, -NR32-, or -C(R33)2-;R32is hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, or -L- heterocycloalkyl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”;each R33is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, Ci- Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”;each Z is independently N or CR2;each R2is independently hydrogen, halogen, -CN, or Ci-Cealkyl independently optionally substituted with one or more R’;- is a single or a double bond;U is N or C;T is N or C; provided that U and T are not both N;Y1is N, NRY1, CR3, or C(R3)2;WSGR Docket No. 66412-753.601each R3is independently hydrogen, halogen, -CN, or Ci-Cealkyl independently optionally substituted with one or more R’;RY1is hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein the alkyl is independently optionally substituted with one or more R’ and wherein the cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”;Y2is N, NRY2, CR4, C(R4)2, or C(=O);each R4is independently hydrogen, halogen, -CN, or Ci-Cealkyl independently optionally substituted with one or more R’;RY2is hydrogen or Ci-Cealkyl independently optionally substituted with one or more R’;Y3is N or C;X1is N or CR5;R5is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, or Ci-Cealkyl independently optionally substituted with one or more R’;X3is N or CR7;R7is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, or Ci-Cealkyl is independently optionally substituted with one or more R’;Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;each R8is independently halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, Ci- Cealkyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”; and / or two R8on the same atom are taken together to form an oxo; andm is 0, 1, 2, 3, or 4;each L1is independently -O-, -S-, -S(=O)-, -S(=O)2-, -NR9-, -C(=O)-, Ci-Cioalkylene, Ci- Cioheteroalkylene, C2-Cealkenylene, C2-Cealkynylene, cycloalkylene, heterocycloalkylene, arylene, or heteroarylene; wherein each alkylene, alkenylene, alkynylene, and heteroalkylene is independently optionally substituted with one or more R’ and wherein each cycloalkylene, heterocycloalkylene, arylene, and heteroarylene is independently optionally substituted with one or more R”;each R9is independently hydrogen or Ci-Cealkyl independently optionally substituted with one or more R’;s is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;⊢— M' is an E3 ubiquitin ligase targeting agent;each Rais independently Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, -L- heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”;each Rbis independently hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L- cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl,WSGR Docket No. 66412-753.601and alkynyl is independently optionally substituted with one or more R’ and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”; each Rcand Rdare independently hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, - L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl independently optionally substituted with one or more R”;L is absent or Ci-Csalkylene optionally substituted with one or more R’; andeach R’ is independently halogen, -CN, -OH, -OCi-Csalkyl, -S(=O)Ci-C3alkyl, -S(=O)2Ci-C3alkyl, -S(=O)2NH2, -S(=O)2NHCi-C3alkyl, -S(=O)2N(Ci-C3alkyl)2, -NH2, -NHCi-C3alkyl, -N(Ci-C3alkyl)2, - NHC(=O)OCi-C3alkyl, -C(=O)Ci-C3alkyl, -C(=O)OH, -C(=O)OCi-C3alkyl, -C(=O)NH2, - C(=O)N(Ci-C3alkyl)2, or -C(=O)NHCi-C3alkyl; wherein each alkyl is independently optionally substituted with one or more halogen;and / or two R’ on the same atom are taken together to form an oxo; andeach R” is independently halogen, -CN, -OH, -OCi-Csalkyl, -S(=O)Ci-C3alkyl, -S(=O)2Ci-C3alkyl, -S(=O)2NH2, -S(=O)2NHCi-C3alkyl, -S(=O)2N(Ci-C3alkyl)2, -NH2, -NHCi-C3alkyl, -N(Ci-C3alkyl)2, - NHC(=O)OCi-C3alkyl, -C(=O)Ci-C3alkyl, -C(=O)OH, -C(=O)OCi-C3alkyl, -C(=O)NH2, - C(=O)N(Ci-C3alkyl)2, -C(=O)NHCi-C3alkyl, Ci-C3alkyl, Ci-C3heteroalkyl, Ci-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more halogen;and / or two R” on the same atom are taken together to form an oxo.

[0108] In some embodiments of a compound of Formula (II), U is N and T is C. In some embodiments of a compound of Formula (II), U is C and T is N. In some embodiments of a compound of Formula (II), U is C and T is C.

[0109] In some embodiments of a compound of Formula (II), Y1is N. In some embodiments of a compound of Formula (II), Y1is NRY1. In some embodiments of a compound of Formula (II), Y1is CR3. In some embodiments of a compound of Formula (II), Y1is C(R3)2.

[0110] In some embodiments of a compound of Formula (II), Y2is N. In some embodiments of a compound of Formula (II), Y2is NRY2. In some embodiments of a compound of Formula (II), Y2is CR4. In some embodiments of a compound of Formula (II), Y2is C(R4)2. In some embodiments of a compound of Formula (II), Y2is C(=O).

[0111] In some embodiments of a compound of Formula (II), Y3is N. In some embodiments of a compound of Formula (II), Y3is C.

[0112] In some embodiments of a compound of Formula (II), X1is N. In some embodiments of a compound of Formula (II), X1is CR5.

[0113] In some embodiments of a compound of Formula (II), X3is N. In some embodiments of a compound of Formula (II), X3is CR7.WSGR Docket No. 66412-753.601

[0114] In some embodiments of a compound of Formula (II),

[00115] In some embodiments of a compound of Formula (II), Y1is NRY1or C(R3)2; and Y2is NRY2, C(R4)2, or C(=O).

[0116] In some embodiments of a compound of Formula (II),within the 6-membered ring containing U, T, X1and X3means that the 6-membered ring is aromatic.

[0117] In some embodiments of a compound of Formula (II),within the 5-membered ring containing U, T, Y1, Y2, and Y3means that the 5 -membered ring is aromatic, partially saturated, or fully saturated.

[0118] In some embodiments of a compound of Formula (II),within the 5-membered ring containing U, T, Y1, Y2, and Y3means that the 5-membered ring is aromatic.

[0119] In some embodiments of a compound of Formula (II),within the 5-membered ring containing U, T, Y1, Y2, and Y3means that the 5-membered ring is partially saturated or fully saturated.

[0120] In some embodiments of a compound of Formula (II),Y x3' isr7

[0121] In some embodiments of a compound of Formula (II),

[0122] In some embodiments of a compound of Formula (II),WSGR Docket No. 66412-753.601

[0123] In some embodiments of a compound of Formula (II),

[0124] In some embodiments of a compound of Formula (II),

[0127] In some embodiments of a compound of Formula (II),Y x3' isWSGR Docket No. 66412-753.601

[0128] In some embodiments of a compound of Formula (II),

[0129] In some embodiments of a compound of Formula (II),

[0130] In some embodiments of a compound of Formula (II),

[0132] In some embodiments of a compound of Formula (II),R7, or

[0133] In some embodiments of a compound of Formula (II),WSGR Docket No. 66412-753.601

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

[0135] In some embodiments of a compound of Formula (II),

[0136] In some embodiments of a compound of Formula (II),

[0137] In some embodiments of a compound of Formula (II), some embodiments of a compound of Formula (II), orWSGR Docket No. 66412-753.601R3° FN" 'N<

[0138] In some embodiments of a compound of Formula (II), R20is 'N In someembodiments of a compound of Formula (II), R20is R31. In some embodiments of a compoundof Formula (II), R20isR31

[0139] In some embodiments of a compound of Formula (II), X is -O-.

[0140] In some embodiments of a compound of Formula (II), R30is hydrogen, Ci-Cealkyl, -L-cycloalkyl, or -L-heterocycloalkyl. In some embodiments of a compound of Formula (II), R30is Ci-C6alkyl.

[0141] In some embodiments of a compound of Formula (II), R31is hydrogen, halogen, -CN, Ci-Cealkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more R’. In some embodiments of a compound of Formula (II), R31is Ci-Cealkyl.

[0142] In some embodiments of a compound of Formula (II), R20is

[0143] In some embodiments of a compound of Formula (II), each Z is independently CR2. In some embodiments of a compound of Formula (II), one Z is N and the remaining Z are independently CR2.R2

[0144] In some embodiments of a compound of Formula (II),. In some R2embodiments of a compound of Formula (II),

[0145] In some embodiments of a compound of Formula (II), each R2is independently hydrogen, halogen, or Ci-Cealkyl independently optionally substituted with one or more R’. In some embodiments of a compound of Formula (II), each R2is independently hydrogen, halogen, or Ci-Cealkyl. In some embodiments of a compound of Formula (II), each R2is independently hydrogen or Ci-Cealkyl. In some embodiments of a compound of Formula (II), each R2is independently hydrogen or halogen. In some embodiments of a compound of Formula (II), each R2is independently hydrogen.

[0146] In some embodiments of a compound of Formula (II),Z Z isWSGR Docket No. 66412-753.601

[0147] In some embodiments of a compound of Formula (II),embodiments of a compound of Formula (II),

[0148] In some embodiments of a compound of Formula (II), the compound is of Formula (Ila):Formula (IIa).

[0149] In some embodiments of a compound of Formula (II), the compound is of Formula (lib):Formula (IIb).

[0150] In some embodiments of a compound of Formula (II), the compound is of Formula (lie):Formula (IIc).

[0151] In some embodiments of a compound of Formula (II), the compound is of Formula (lid):Formula (IId) wherein Y1is NRY1or C(R3)2.WSGR Docket No. 66412-753.601

[0152] In some embodiments of a compound of Formula (lid), Y1is NRY1. In some embodiments of a compound of Formula (lid), Y1is C(R3)2.

[0153] In some embodiments of a compound of Formula (Ila)-(IId), X3is N. In some embodiments of a compound of Formula (Ila)-(IId), X3is CR7.

[0154] In some embodiments of a compound of Formula (II), (lie), or (lid), each R3is independently hydrogen, halogen, or Ci-Cealkyl independently optionally substituted with one or more R’. In some embodiments of a compound of Formula (II), (lie), or (lid), each R3is independently hydrogen or Ci-Cealkyl. In some embodiments of a compound of Formula (II), (lie), or (lid), each R3is independently Ci-Cealkyl. In some embodiments of a compound of Formula (II), (lie), or (lid), each R3is independently hydrogen.

[0155] In some embodiments of a compound of Formula (II), (Ila), (lib), or (lid), RY1is hydrogen, Ci-Cealkyl, or -L-cycloalkyl; wherein each alkyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl is independently optionally substituted with one or more R”. In some embodiments of a compound of Formula (II), (Ila), (lib), or (lid), RY1is hydrogen or Ci-Cealkyl independently optionally substituted with one or more R’. In some embodiments of a compound of Formula (II), (Ila), (lib), or (lid), RY1is hydrogen or Ci-Cealkyl. In some embodiments of a compound of Formula (II), (Ila), (lib), or (lid), RY1is Ci-Cealkyl.

[0156] In some embodiments of a compound of Formula (II) or (Ila), each R4is independently hydrogen, halogen, or Ci-Cealkyl. In some embodiments of a compound of Formula (II) or (Ila), each R4is independently hydrogen.

[0157] In some embodiments of a compound of Formula (II), RY2is hydrogen or Ci-Cealkyl.

[0158] In some embodiments of a compound of Formula (II), R5is hydrogen, halogen, or Ci-Cealkyl independently optionally substituted with one or more R’. In some embodiments of a compound of Formula (II), R5is hydrogen or Ci-Cealkyl. In some embodiments of a compound of Formula (II), R5is hydrogen.

[0159] In some embodiments of a compound of Formula (II) or (Ila)-(IId), R7is hydrogen, halogen, or Ci-Cealkyl is independently optionally substituted with one or more R’. In some embodiments of a compound of Formula (II) or (Ila)-(IId), R7is hydrogen or Ci-Cealkyl. In some embodiments of a compound of Formula (II) or (Ila)-(IId), R7is hydrogen. In some embodiments of a compound of Formula (II) or (Ila)-(IId), R7is Ci-Cealkyl.

[0160] In some embodiments of a compound of Formula (II) or (Ila)-(IId), Ring A is aryl or heteroaryl. In some embodiments of a compound of Formula (II) or (Ila)-(IId), Ring A is phenyl or 5- or 6-membered heteroaryl. In some embodiments of a compound of Formula (II) or (Ila)-(IId), Ring A is phenyl. In some embodiments of a compound of Formula (II) or (Ila)-(IId), Ring A is 6-membered heteroaryl. In some embodiments of a compound of Formula (II) or (Ila)-(IId), Ring A is pyridinyl, pyrimidinyl, pyrazinyl, or pyridazinyl. In some embodiments of a compound of Formula (II) or (Ila)-(Ild), Ring A is pyridinyl, pyrimidinyl, or pyrazinyl. In some embodiments of a compound of Formula (II) or (Ila)-(IId), Ring A is pyridinyl. In some embodiments of a compound of Formula (II) or (Ila)-(IId),WSGR Docket No. 66412-753.601Ring A is pyridazinyl. In some embodiments of a compound of Formula (II) or (Ila)-(IId), Ring A is 5-membered heteroaryl. In some embodiments of a compound of Formula (II) or (Ila)-(IId), Ring A is phenyl or pyridinyl.

[0161] In some embodiments of a compound of Formula (II) or (Ila)-(IId), each R8is independently halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)NRcRd, or Ci-Cealkyl independently optionally substituted with one or more R’. In some embodiments of a compound of Formula (II) or (Ila)-(IId), each R8is independently halogen, -CN, -ORa, -C(=O)NRcRd, or Ci-Cealkyl. In some embodiments of a compound of Formula (II) or (Ila)-(IId), each R8is independently halogen, -C(=O)NRcRd, or Ci-Cealkyl. In some embodiments of a compound of Formula (II) or (Ila)-(IId), each R8is independently -C(=O)NRcRd. In some embodiments of a compound of Formula (II) or (Ila)-(IId), each R8is independently halogen or -C(=O)NRcRd. In some embodiments of a compound of Formula (II) or (Ila)-(IId), each R8is independently halogen or -C(=O)NH(heteroaryl) wherein the heteroaryl is independently optionally substituted with one or more R”. In some embodiments of a compound of Formula (II) or (Ila)-(IId), each R8is independently -C(=O)NH(heteroaryl) wherein the heteroaryl is independently optionally substituted with one or more R”.

[0162] In some embodiments of a compound of Formula (II) or (Ila)-(IId), m is 1, 2, or 3. In some embodiments of a compound of Formula (II) or (Ila)-(IId), m is 1 or 2. In some embodiments of a compound of Formula (II) or (Ila)-(IId), m is 0. In some embodiments of a compound of Formula (II) or (Ila)-(IId), m is. In some embodiments of a compound of Formula (II) or (Ila)-(IId), m is 2.

[0163] In some embodiments of a compound of Formula (II) or (Ila)-(IId),O z \( CH, wherein:Ring C is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;each R” is independently halogen, -CN, -OH, -OCi-Csalkyl, -S(=O)Ci-C3alkyl, -S(=O)2Ci-C3alkyl, -S(=O)2NH2, -S(=O)2NHCi-C3alkyl, -S(=O)2N(Ci-C3alkyl)2, -NH2, -NHCi-C3alkyl, -N(Ci-C3alkyl)2, - NHC(=O)OCi-C3alkyl, -C(=O)Ci-C3alkyl, -C(=O)OH, -C(=O)OCi-C3alkyl, -C(=O)NH2, - C(=O)N(Ci-C3alkyl)2, -C(=O)NHCi-C3alkyl, Ci-C3alkyl, Ci-C3heteroalkyl, Ci-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more halogen;and / or two R” on the same atom are taken together to form an oxo; andu is 0, 1, 2, 3, or 4.WSGR Docket No. 66412-753.601

[0164] In some embodiments of a compound of Formula (II) or (Ila)-(IId), is(R")u, wherein:Ring C is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;R8ais hydrogen, halogen, -CN, Ci-Cealkyl, or Ci-Cehaloalkyl;each R” is independently halogen, -CN, -OH, -OCi-Csalkyl, -S(=O)Ci-C3alkyl, -S(=O)2Ci-C3alkyl, -S(=O)2NH2, -S(=O)2NHCi-C3alkyl, -S(=O)2N(Ci-C3alkyl)2, -NH2, -NHCi-C3alkyl, -N(Ci-C3alkyl)2, - NHC(=O)OCi-C3alkyl, -C(=O)Ci-C3alkyl, -C(=O)OH, -C(=O)OCi-C3alkyl, -C(=O)NH2, - C(=O)N(Ci-C3alkyl)2, -C(=O)NHCi-C3alkyl, Ci-C3alkyl, Ci-C3heteroalkyl, Ci-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more halogen;and / or two R” on the same atom are taken together to form an oxo; andu is 0, 1, 2, 3, or 4.Ring C is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;R8ais hydrogen, halogen, -CN, Ci-Cealkyl, or Ci-Cehaloalkyl;WSGR Docket No. 66412-753.601each R” is independently halogen, -CN, -OH, -OCi-Csalkyl, -S(=O)Ci-C3alkyl, -S(=O)2Ci-C3alkyl, -S(=O)2NH2, -S(=O)2NHCi-C3alkyl, -S(=O)2N(Ci-C3alkyl)2, -NH2, -NHCi-C3alkyl, -N(Ci-C3alkyl)2, - NHC(=O)OCi-C3alkyl, -C(=O)Ci-C3alkyl, -C(=O)OH, -C(=O)OCi-C3alkyl, -C(=O)NH2, - C(=O)N(Ci-C3alkyl)2, -C(=O)NHCi-C3alkyl, Ci-C3alkyl, Ci-C3heteroalkyl, Ci-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more halogen;and / or two R” on the same atom are taken together to form an oxo; andu is 0, 1, 2, 3, or 4.IS

[0168] In some embodiments, Ring C is a heteroaryl. In some embodiments, Ring C is a 5 -membered heteroaryl. In some embodiments, Ring C is a 5 -membered heteroaryl comprising one or two heteroatoms selected from the group consisting of N, O, and S. In some embodiments, Ring C is a 5-membered heteroaryl comprising one or two heteroatoms selected from the group consisting ofN and O. In some embodiments, Ring C is a 5-membered heteroaryl comprising one or two heteroatoms that are N.

[0169] In some embodiments, u is 0, 1, or 2. In some embodiments, u is 1 or 2. In some embodiments, u is 0. In some embodiments, u is 1. In some embodiments, u is 2.

[0170] In some embodiments, R8ais hydrogen, halogen, or Ci-Cealkyl. In some embodiments, R8ais hydrogen or halogen. In some embodiments, R8ais hydrogen, halogen, or Ci-Cealkyl. In some embodiments, R8ais hydrogen. In some embodiments, R8ais hydrogen, halogen, or Ci-Cealkyl. In some embodiments, R8ais halogen, -CN, Ci-Cealkyl, or Ci-Cehaloalkyl. In some embodiments, R8ais halogen, Ci-Cealkyl, or Ci-Cehaloalkyl. In some embodiments, R8ais halogen or Ci-Cealkyl. In some embodiments, R8ais halogen.(R8),

[0171] In some embodiments of a compound of Formula (II) or (Ila)-(IId),WSGR Docket No. 66412-753.601In some embodiments of a compound of Formula (II) or (Ila)-(IId),

[0172] In some embodiments of a compound of Formula (II) or (Ila)-(IId),

[0173] In some embodiments of a compound of Formula (II) or (Ila)-(IId),

[0174] In some embodiments of a compound of Formula (II) or (Ila)-(IId),O F O O

[0175] In some embodiments of a compound of Formula (II) or (Ila)-(IId),

[0176] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -NR9-, -C(=O)-, Ci-Cioalkylene, Ci-Cioheteroalkylene, cycloalkylene, or heterocycloalkylene; wherein each alkylene and heteroalkylene is independently optionally substituted with one or more R’ and wherein each cycloalkylene and heterocycloalkylene is independently optionally substituted with one or more R”. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -NR9-, -C(=O)-, Ci-Cioalkylene, Ci-Cioheteroalkylene,WSGR Docket No. 66412-753.601cycloalkylene, or heterocycloalkylene. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-Cioalkylene, Ci-Cioheteroalkylene, cycloalkylene, or heterocycloalkylene. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, Ci-Cioalkylene, Ci-Cioheteroalkylene, cycloalkylene, or heterocycloalkylene.

[0177] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),each L1is independently -O-, -C(=O)-, Ci-Cioalkylene, or heterocycloalkylene; oreach L1is independently -O-, Ci-Cioalkylene, Ci-Cioheteroalkylene, or heterocycloalkylene; or each L1is independently -O-, Ci-Cioalkylene, or heterocycloalkylene; oreach L1is independently Ci-Cioalkylene or heterocycloalkylene; oreach L1is independently Ci-Cioalkylene, cycloalkylene, or heterocycloalkylene; oreach L1is independently -O-, cycloalkylene, or heterocycloalkylene; oreach L1is independently -O-, Ci-Cioalkylene, cycloalkylene, or heterocycloalkylene.

[0178] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),each L1is independently -O-, -C(=O)-, Ci-Cealkylene, or heterocycloalkylene; oreach L1is independently -O-, Ci-Cealkylene, Ci-Ceheteroalkylene, or heterocycloalkylene; or each L1is independently -O-, Ci-Cealkylene, or heterocycloalkylene; oreach L1is independently Ci-Cealkylene or heterocycloalkylene; oreach L1is independently Ci-Cealkylene, cycloalkylene, or heterocycloalkylene; oreach L1is independently -O-, cycloalkylene, or heterocycloalkylene; oreach L1is independently -O-, Ci-Cealkylene, cycloalkylene, or heterocycloalkylene.

[0179] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),each L1is independently -O-, -C(=O)-, Ci-C4alkylene, or heterocycloalkylene; oreach L1is independently -O-, Ci-C4alkylene, Ci-C4heteroalkylene, or heterocycloalkylene; or each L1is independently -O-, Ci-C4alkylene, or heterocycloalkylene; oreach L1is independently Ci-C4alkylene or heterocycloalkylene; oreach L1is independently Ci-C4alkylene, cycloalkylene, or heterocycloalkylene; oreach L1is independently -O-, cycloalkylene, or heterocycloalkylene; oreach L1is independently -O-, Ci-C4alkylene, cycloalkylene, or heterocycloalkylene.

[0180] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),each L1is independently -O-, -C(=O)-, Ci-Cioalkylene, or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N; or each L1is independently -O-, Ci-Cioalkylene, Ci-Cioheteroalkylene, or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N; oreach L1is independently -O-, Ci-Cioalkylene, or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N; orWSGR Docket No. 66412-753.601each L1is independently Ci-Cioalkylene or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N; oreach L1is independently Ci-Cioalkylene, Cs-C. cycloalkylcnc. or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N; oreach L1is independently -O-, Cs-C. cycloalkylcnc. or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N; or each L1is independently -O-, Ci-Cioalkylene, Cs-C. cycloalkylcnc. or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N.

[0181] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),each L1is independently -O-, -C(=O)-, Ci-Cealkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms one or two heteroatoms that are N; oreach L1is independently -O-, Ci-Cealkylene, Ci-Ceheteroalkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N; oreach L1is independently -O-, Ci-Cealkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N; oreach L1is independently Ci-Cealkylene or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N; oreach L1is independently Ci-Cealkylene, Cs-C. cycloalkylcnc. or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N; oreach L1is independently -O-, C3-C6cycloalkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N; oreach L1is independently -O-, Ci-Cealkylene, Cs-C. cycloalkylcnc. or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N.

[0182] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),each L1is independently -O-, -C(=O)-, Ci-C4alkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms one or two heteroatoms that are N; oreach L1is independently -O-, Ci-C4alkylene, Ci-C4heteroalkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N; oreach L1is independently -O-, Ci-C4alkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N; oreach L1is independently Ci-C4alkylene or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N; oreach L1is independently C1-C4alkylene, C3-C6cycloalkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N; oreach L1is independently -O-, C3-C6cycloalkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N; orWSGR Docket No. 66412-753.601each L1is independently -0-, Ci-C4alkylene, Cs-C. cycloalkylcnc. or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N.

[0183] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-Cioalkylene, or heterocycloalkylene.

[0184] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-Cealkylene, or heterocycloalkylene.

[0185] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-C4alkylene, or heterocycloalkylene.

[0186] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-Cioalkylene, or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N.

[0187] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-Cealkylene, or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N.

[0188] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-C4alkylene, or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N.

[0189] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-Cioalkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms one or two heteroatoms that are N.

[0190] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-Cealkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms one or two heteroatoms that are N.

[0191] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-C4alkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms one or two heteroatoms that are N.

[0192] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-Cioalkylene, cycloalkylene, or heterocycloalkylene.

[0193] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-Cealkylene, cycloalkylene, or heterocycloalkylene.

[0194] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-C4alkylene, cycloalkylene, or heterocycloalkylene.

[0195] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-Cioalkylene, or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N.

[0196] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-Cealkylene, Cs-Cecycloalkylene, or 3-to 12-memberedWSGR Docket No. 66412-753.601heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N.

[0197] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-C4alkylene, Cs-Cecycloalkylene, or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N.

[0198] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-Cioalkylene, Cs-Cecycloalkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms one or two heteroatoms that are N.

[0199] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-Cealkylene, Cs-Cecycloalkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms one or two heteroatoms that are N.

[0200] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, -C(=O)-, Ci-C4alkylene, Cs-C. cycloalkylcnc. or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms one or two heteroatoms that are N.

[0201] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, Ci-Cioalkylene, cycloalkylene, or heterocycloalkylene.

[0202] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, Ci-Cealkylene, cycloalkylene, or heterocycloalkylene.

[0203] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, Ci-C4alkylene, cycloalkylene, or heterocycloalkylene.

[0204] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, Ci-Cioalkylene, Cs-C. cycloalkylcnc. or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N.

[0205] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, Ci-Cealkylene, Cs-C. cycloalkylcnc. or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N.

[0206] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, Ci-C4alkylene, Cs-C. cycloalkylcnc. or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N.

[0207] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, Ci-Cioalkylene, Cs-C. cycloalkylcnc. or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms one or two heteroatoms that are N.

[0208] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, Ci-Cealkylene, Cs-C. cycloalkylcnc. or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms one or two heteroatoms that are N.WSGR Docket No. 66412-753.601

[0209] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), each L1is independently -O-, Ci-C4alkylene, Cs-Cecycloalkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms one or two heteroatoms that are N.

[0210] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 1, 2, 3, 4, 5, or 6. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 1, 2, 3, or 4. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 4, 5, 6, 7, 8, 9, or 10. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 6, 7, 8, 9, or 10. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 1. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 2. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 3. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 4. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 5. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 6. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(Ild), s is 7. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 8. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 9. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 10.

[0211] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 3, 4, 5, or 6. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 4, 5, or 6. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 3, 4, or 5. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), s is 4 or 5.WSGR Docket No. 66412-753.601. In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),WSGR Docket No. 66412-753.601

[0212] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), the E3 ligase targeting agent is a cereblon E3 ligase, a VHL E3 ligase, a MDM2 ligase, a TRIM24 ligase, a TRIM21 ligase, a KEAP1 ligase, or an IAP ligase.

[0213] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), the E3 ligase targeting agent is a cereblon E3 ligase.| — M

[0214] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),* is (R10)tIO Formula (A);wherein:Y is CH, CD, C(CH3), C(CD3), or N;W is absent, -O-, -NRb-, or -C(=O)NRC-;Ring B is absent, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;each R10is independently halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, Ci- Cealkyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”; and / or two R10on the same atom are taken together to form an oxo; andt is 0, 1, 2, 3, 4, 5, or 6.

[0215] In some embodiments of a compound of Formula (A), Y is CH or N. In some embodiments of a compound of Formula (A), Y is CH. In some embodiments of a compound of Formula (A), Y is CH or CD. In some embodiments of a compound of Formula (A), Y is N. In some embodiments of a compound of Formula (A), Y is CD. In some embodiments of a compound of Formula (A), Y is C(CH3) or C(CD3). In some embodiments of a compound of Formula (A), Y is C(CH3).WSGR Docket No. 66412-753.601

[0216] In some embodiments of a compound of Formula (A), W is absent. In some embodiments of a compound of Formula (A), W is -O-. In some embodiments of a compound of Formula (A), W is -NRb-. In some embodiments of a compound of Formula (A), W is -C(=O)NRC-.

[0217] In some embodiments of a compound of Formula (A), Ring B is absent. In some embodiments of a compound of Formula (A), Ring B is heterocycloalkyl. In some embodiments of a compound of Formula (A), Ring B is aryl or heteroaryl. In some embodiments of a compound of Formula (A), Ring B is aryl. In some embodiments of a compound of Formula (A), Ring B is heteroaryl. In some embodiments of a compound of Formula (A), Ring B is a 5 - to 6-membered heteroaryl comprising one, two, or three heteroatoms selected from the group consisting of N, O, and S. In some embodiments of a compound of Formula (A), Ring B is a 5-membered heteroaryl comprising one, two, or three heteroatoms selected from the group consisting of N, O, and S. In some embodiments of a compound of Formula (A), Ring B is a 6-membered heteroaryl comprising one, two, or three heteroatoms that are N.

[0218] In some embodiments of a compound of Formula (A), Ring B is an 8- to 12-membered heteroaryl comprising one, two, or three heteroatoms selected from the group consisting ofN, O, and S.

[0219] In some embodiments of a compound of Formula (A), Ring B is a 9- to 10-membered heteroaryl comprising one, two, or three heteroatoms selected from the group consisting ofN, O, and S.

[0220] In some embodiments of a compound of Formula (A), Ring B is an 8- to 12-membered heteroaryl comprising one, two, or three heteroatoms that are N.

[0221] In some embodiments of a compound of Formula (A), Ring B is a 9- to 10-membered heteroaryl comprising one, two, or three heteroatoms that are N.

[0222] In some embodiments of a compound of Formula (A), Ring B isIn some embodiments of a compound of Formula (A), Ring B is. In some embodiments of acompound of Formula (A), Ring B is. In some embodiments of a compound of Formula (A),Ring Bis AHNN

[0223] In some embodiments of a compound of Formula (A), each R10is independently halogen, -CN, -OH, -ORa, -NRcRd, Ci-Cealkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”; and / or two R10on the same atom are taken together to form an oxo. In some embodiments of a compound of Formula (A), each R10is independently halogen, -ORa, or Ci-Cealkyl; and / or two R10on the same atom are taken together to formWSGR Docket No. 66412-753.601an oxo. In some embodiments of a compound of Formula (A), two R10on the same atom are taken together to form an oxo. In some embodiments of a compound of Formula (A), each R10is independently halogen, -0Ra, or Ci-Cealkyl. In some embodiments of a compound of Formula (A), each R10is independently halogen or Ci-Cealkyl. In some embodiments of a compound of Formula (A), each R10is independently halogen.

[0224] In some embodiments of a compound of Formula (A), t is 0, 1, 2, 3, or 4. In some embodiments of a compound of Formula (A), t is 1, 2, 3, 4, 5, or 6. In some embodiments of a compound of Formula (A), t is 2, 3, 4, 5, or 6. In some embodiments of a compound of Formula (A), t is 2, 3, 4, or 5. In some embodiments of a compound of Formula (A), t is 1, 2, 3, or 4. In some embodiments of a compound of Formula (A), t is 2, 3, or 4. In some embodiments of a compound of Formula (A), t is 2. In some embodiments of a compound of Formula (A), t is 3. In some embodiments of a compound of Formula (A), t is 4.WSGR Docket No. 66412-753.601ClWSGR Docket No. 66412-753.601

[0226] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),isWSGR Docket No. 66412-753.601

[0228] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),’ is

[0229] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),is F

[0230] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),* isWSGR Docket No. 66412-753.601

[0231] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), is F

[0232] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),is

[0233] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),isWSGR Docket No. 66412-753.601

[0235] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),

[0236] In some embodiments of a compound of Formula (I), (la) -(Id), (II), or (Ila)-(IId),isWSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601

[0238] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId), isor

[0239] In some embodiments of a compound of Formula (I), (la)-(Id), (II), or (Ila)-(IId),is

[0240] In some embodiments of a compound disclosed herein, each Rais independently Ci-Cealkyl, Ci-Ceheteroalkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl and heteroalkyl is independently optionally substituted with one or more R’ and each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”. In some embodiments of a compound disclosed herein, each Rais independently Ci-Cealkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more R’ and each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”. In some embodiments of aWSGR Docket No. 66412-753.601compound disclosed herein, each Rais independently Ci-Cealkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more R’. In some embodiments of a compound disclosed herein, each Rais independently Ci-Cealkyl independently optionally substituted with one or more R’. In some embodiments of a compound disclosed herein, each Rais independently Ci-Cealkyl or Ci-Cehaloalkyl. In some embodiments of a compound disclosed herein, each Rais independently Ci-Cealkyl.

[0241] In some embodiments of a compound disclosed herein, each Rbis independently hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl and heteroalkyl is independently optionally substituted with one or more R’ and each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”. In some embodiments of a compound disclosed herein, each Rbis independently hydrogen, Ci-Cealkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more R’ and each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”. In some embodiments of a compound disclosed herein, each Rbis independently hydrogen, Ci-Cealkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more R’. In some embodiments of a compound disclosed herein, each Rbis independently hydrogen or Ci-Cealkyl independently optionally substituted with one or more R’. In some embodiments of a compound disclosed herein, each Rbis independently hydrogen, Ci-Cealkyl, or Ci-Cehaloalkyl. In some embodiments of a compound disclosed herein, each Rbis independently hydrogen, or Ci-Cealkyl. In some embodiments of a compound disclosed herein, each Rbis hydrogen. In some embodiments of a compound disclosed herein, each Rbis independently Ci-Cealkyl.

[0242] In some embodiments of a compound disclosed herein, each Rcand Rdare independently hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl and heteroalkyl is independently optionally substituted with one or more R’ and each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”. In some embodiments of a compound disclosed herein, each Rcand Rdare independently hydrogen, Ci-Cealkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more R’ and each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”. In some embodiments of a compound disclosed herein, each Rcand Rdare independently hydrogen, Ci-Cealkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more R’. In some embodiments of a compound disclosed herein, each Rcand Rdare independently hydrogen or Ci-Cealkyl independently optionally substituted with one or more R’. In some embodiments of a compound disclosed herein, each Rcand Rdare independently hydrogen, Ci-Cealkyl, or Ci-Cehaloalkyl. In some embodiments of a compound disclosed herein, each Rcand Rdare independently hydrogen or Ci-Cealkyl. In some embodiments of a compound disclosed herein, each Rcand Rdare hydrogen. In some embodiments of a compound disclosed herein, each Rcand Rdare independently Ci-Cealkyl.WSGR Docket No. 66412-753.601

[0243] In some embodiments of a compound disclosed herein, Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl independently optionally substituted with one or more R”.

[0244] In some embodiments of a compound disclosed herein, L is absent or C₁-C₃alkylene. In some embodiments of a compound disclosed herein, L is absent. In some embodiments of a compound disclosed herein, L is absent or -CH₂-. In some embodiments of a compound disclosed herein, L is C₁-C₃alkylene. In some embodiments of a compound disclosed herein, L is -CH₂-. In some embodiments of a compound disclosed herein, L is -CH₂CH₂-. In some embodiments of a compound disclosed herein, L is -CH₂CH₂CH₂-.

[0245] In some embodiments of a compound disclosed herein, each R’ is independently halogen, -CN, -OH, -OCi-Csalkyl, -NH2, -NHCi-Csalkyl, or -N(Ci-C3alkyl)2; wherein each alkyl is independently optionally substituted with one or more halogen; and / or two R’ on the same atom are taken together to form an oxo. In some embodiments of a compound disclosed herein, each R’ is independently halogen, -CN, -OH, -OCi-Csalkyl, -NH2, -NHCi-Csalkyl, or -N(Ci-C3alkyl)2; wherein each alkyl is independently optionally substituted with one or more halogen; and / or two R’ on the same atom are taken together to form an oxo. In some embodiments of a compound disclosed herein, each R’ is independently halogen, -CN, -OH, -OC 1 -Chalky I. or -NH2; wherein each alkyl is independently optionally substituted with one or more halogen; and / or two R’ on the same atom are taken together to form an oxo. In some embodiments of a compound disclosed herein, each R’ is independently halogen, -CN, -OH, -OC’i-Ckalkyl. or -NH2; and / or two R’ on the same atom are taken together to form an oxo. In some embodiments of a compound disclosed herein, each R’ is independently halogen, -CN, -OH, -OC’i-Ckalkyl. or -NH2. In some embodiments of a compound disclosed herein, each R’ is independently halogen.

[0246] In some embodiments of a compound disclosed herein, each R” is independently halogen, -CN, -OH, -OCi-C3alkyl, -NH2, -NHCi-C3alkyl, -N(Ci-C3alkyl)2, Ci-C3alkyl, Ci-C3heteroalkyl, Ci-Cecycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more halogen; and / or two R” on the same atom are taken together to form an oxo. In some embodiments of a compound disclosed herein, each R” is independently halogen, -CN, -OH, -OC 1 -Ckalky 1, -NH2, or Ci -Ckalky 1; wherein each alkyl is independently optionally substituted with one or more halogen; and / or two R” on the same atom are taken together to form an oxo. In some embodiments of a compound disclosed herein, each R” is independently halogen, -CN, -OH, -OCi -Ckalky 1, -NH2, or Ci -Ckalkyl: and / or two R” on the same atom are taken together to form an oxo. In some embodiments of a compound disclosed herein, each R” is independently halogen, -CN, -OH, -OCi-Ckalkyl. -NH2, or Ci-Ckalkyl. In some embodiments of a compound disclosed herein, each R” is independently halogen or Ci-Ckalkyl. In some embodiments of a compound disclosed herein, each R” is independently halogen. In some embodiments of a compound disclosed herein, each R” is independently Ci-Ckalkyl.

[0247] Any combination of the groups described above for the various variables is contemplated herein. Throughout the specification, groups and substituents thereof are chosen by one skilled in the field to provide stable moieties and compounds.WSGR Docket No. 66412-753.601

[0248] In some embodiments the compound disclosed herein, is selected from a compound found in table 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.Z X zTable 1 kk\\ \ \ z zEx. Structu \ \ z—r zie1X 9 X0 X^?° z11 J o oo-Z / —.XX2 f0°Z\ TZoZ. z—'^X 'oXx1 1 £ I °oZ°3 / \ _ Z>n O~OV \ V Z z TZ ' K)\-- \ \\\z z \4WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601Ex. Structure0 10H2NAD ATH0HKk^O / XMA0 T 0 z z z N> Akk z\\\ \ \ \ x z z \- T / ° H k\ NAI-A M \ x°^ / < ° JA j kJL / v / yo \ < z— ZI v / ^\ lZx / °y j^Z^ zzy / =\==k n 11 Q 0 > / A / ‘ ( ° / \ y °\= A Q 4Zx.kk )P>oz zA © A4° o^?^°° o zA 11 \ o i o > A / °o' crj 1 oz-Z ^ / —.k A0vz / —.ikoz-z\120^A>> c ozz^> ozOO / K < i <rrro o o Cr o o 131415WSGR Docket No. 66412-753.601Ex. Structure16z \k\ \ z17J b 1 \^’Z J—.o i:- \ / °=^o / \z ZI18Z Z—'-*oxx1 1 X X ° °0 \ \ z X Z —Z I / 19\ \\\z z \™C°NH2oH 020 0O HN.,A0" ^j°r.< tW ^x 0^ NZH J.0WSGR Docket No. 66412-753.601Ex. Structure21X I)Xz)o=o22° / \ 4 Z.^rj oz^ °Z~ \Z- 23 H / Oo^N-f0 / 7Nof O °.\ X < M CO Z0r ^ 04 o Z=. ( \ _ \ _ / \ o Q"XNH* 6\ / \ X _ I VHN. O l / z'~ ""v— / x^ oNIT 0N\ / =\ Z / '0UUA H,<2 CN- z\o=04 Oz\ X 0H2NAD rvTMV / S0_-N / V\ / N-'Z''AHN^O / F XMAO T r0H N< VN / =\ KN / 2526 oHN^Z°0=^ >HzN^v^ t / 7Vol.<yN^7v^NXoI / 0NATN\ / =\ JLN / WSGR Docket No. 66412-753.601Ex. Structure27 o HN— / 0 0=K / ”■■"0HN.,0 / |I / 0NATN\ / =\ AN / yJk / VA yo28 0L JNxj' VK / 0NH HN^.0 9". N^ / N~\ ¥o N^VNV / =\ AN / ° kJL / vJ^ yo29 0L J r / '0)^NH HN.,0 / °" / N'VN\ )=O r °zNATN\ / =\ J^N / °30 o HN^f0> ¥0.-O-N--¥¥' HN^O / w|Nr / ° NA¥N\ / =\ JLN / 31 o HN^°0=X\ >HN.,0 / o O-¥ |I / 0N<krN / =\ XN / 32 O 0. HH ¥NH2NI) / X>-N1HN^O / °"<x' / F[ / 0NATN\ / " A ANkJt¥ V¥ y6XWSGR Docket No. 66412-753.601Ex. Structure33VXzX n A kkzz=\0° ° / \ / \ / 4 4 z zz^x,,1 \34 \ 11313Xxk J ' '"" OO■xx0k pXkopz~ -?~-xk7*0p ° °zz- | —7 oz~- \\O ' y z) O k350 JIZzN 0 ° O 0 / / -.N"' P, N5. o O -PpP p ■ X Ox H / F H0 0 1 / ° N<;xN\ / =v_AkXjLx / P P ko36 0H2N'' yX 0™v°h Hlk 0 37 OHsN'SX 0X XN4Jok N^ 2p H O38WSGR Docket No. 66412-753.601Ex. Structure39X X X M NJz z z^ ) )ooo===40 AA K k° / \ 444 Z z Z^KK,JV°'K0 rj o 6 z4 A / O°Z^K-^ ^^^=7'..: •°o4 °zzz"-~ / 1 / < V <\\ / SO / ^0 o / ZIzf o < O> o o / .QOKZk 6 o o 42z%^v / °^XAz ZCM z\ °^X43HN^>AY^N°NA HN^O / J>'VJn / irV / \—y / X y-N C,<F0 FoXjWSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601Ex. Structure65HN—? 0 F O= / \ oH'AOHN,, O / | A NA 1ATV / A / A / Jy °A66HN—? O F O=< \ o ”AO I A?HN^O / / 0|670 0=o? HN-O ) "'Y HN.i[,0T / / wI \ / 0| NN" A A / A^i / yo68 o HN~? A P HN. [,0N / / AT ^V0| N '=VJLN / A / AA / yo69 o HNy A A / X r / oJ'N-Qr A1 oNHN. I,0T / YNN\ A A0|I / ~NX70 oy o HNAo F \ "'Y HN.i1,0 / YOo0-G? |N Ar? A A7AAAJ yoWSGR Docket No. 66412-753.601Ex. Structure71 p HN^Z 0 F O=< \HN^O / |[ / 0N ITN\ / " A AAA / y72 p HNA'0°A >H2NAO rv¥> Y ¥ o.. o - NNT / 0N<#VN / =\ XN / 73 p HN-¥0°A >HINAFAO rvCA1 / O'”\ / ¥ / —N\Hx—NA N.,0 / |1 / °N ITN\ / ^A A / AAAAO74 P HN¥'0°A > ''NAA _ ¥WHAA / A HN.,0 | N"yr\ AA yoAAA¥ \— / VNX075 p HNA' 7-,,^.r'¥NHrN-^P / o.. O', NC^v 1NA T ' / AA / 0N7 / UuA / yoWSGR Docket No. 66412-753.601Ex. Structure76I N>zH r # \ / # \ / x\\ 77 \ \°== _ _\^ O °= r\4 4 ZZK^^~xJ <°oK / \77 o HN— f00= / )IrjNQZ zz^szz-'V °"OZH~-z\\~X c-o XHN^ ^O _ / °^ '*=7 |) ■H OV W o °Z” U\ / "?\ — / \-Nx9f 0 A^ olv Z [ z\ zz78 °lz - o A \JG H oHzN Z— / °0=K / ^33H2NV) oTp7F" T o-O '> NX^XNr / 0N^W / =\ XN / 798081t,.z4:yO>^is4”CH 0WSGR Docket No. 66412-753.601Ex. Structure82 0HN'AR 'MV MV V \\ / \ / \ / / \ / / / \ / / (\\\\ 77 ( 77 ( \ \ \ \==== _ _ _ _ VF\ \^x'( O o °°° / / / =====\\\ A A A A A zzZz^,9 J V AVJoxx. AH^O 6 A °!0 AA 9 & zt 99. • k° >v v>o°AAr- ■y r AV ° o ° °°zzFF 0zcy.--- / 83 r ~zf " H "" O."" °Av- / / J / zz TZ TZ IZ J TZ o o O O O84858687WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601Ex. Structure93H Hro94 o HN^Z A 1 rj F. yw0=^A / N^ A U1 / N / N HN^O 9"(^N^ |V\ / / =\ 50XNX95 f o.HN0=\—^ / o Vi Fx< / / IZ A o / ^AAAIHN^O / |NA 1N / X / =\ A ° N / 96J "NA 1N / X ^\ A0'NzUL / o yoX97 0HN^CF\ ~Cl VFy?HJyo0NITN^V=V^Z0oWSGR Docket No. 66412-753.601Ex. Structure98 0HNXR 'Iz \O n -n= rFV H^O \^ °= nn 0N<TTN\ / =\ 0 A z099c& ” vY XZ"0)\ °100 O F=^A " X HI30 Xj XXuXK N H^4 O 101WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601Ex. Structure106 o HN— v" V / WOAJON HN^.0 9"(^ 7N<°= / \XT ZI"..N\ / =\ A'N^FT A A. '107 00 A z HNA> °VY-oF\ [ I° z- _ '■vFZA.^V1. J ’Hll^O0A Mh XI1N<TTN\ / =\ o / \ —X \ o.1 0 Q 4\ o108 / z' / LLZ ' z VO I1091— N. XVFFoA / N HX 0 110 O FFy o JM y / MA \— / \-Nx0WSGR Docket No. 66412-753.601Ex. StructureIll 0 FH2NAy il oMV >\ °\=N HX 0 112 F OIoXz-\ / X C-n°\^YH O Z z^ 113 Y1o Y / o, _rf. X X- "Y Yo Y “■6)\ °=( o=CM zX114N^Y _ _' J XV4 / / >^NH HL.0F° NATN\ / =\ AN / J^YXY y 6115WSGR Docket No. 66412-753.601Ex. Structure116 o HNA A HN^ ^O 9"(^ yT / —0NAT\ / =\ XN / 117 0HN A°^ _ / > N 1AHily> °N< =A A / A4 rrAA A_ / / 0Ao. “■.~6 oGN118zAs ^)\ °=M ox^ZTA ©u- / HV O119WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601Ex. Structure125I toZVo -n126 oZ06 z o > V°yo AA Oz- 0 V \ j U_O127 Vg \r zx “g k / . O z 1 / zxHZNF" JJV< 0X / J / °T N^ XzH. °f. - N 0z[A r / f "" o, / r?[ $“ ^z ^ / iz J 6 C Q '" o o / z^NzA- 2 \(Z~ / ' H O 1 8)\ )\= / ( O l / LAzX° °==z zI(\ O U-J_CM= °=CMx zI ^129H2NO=Z \ O HN^Z 0 F"\51 1 / O'';$ / ^X / ’A. N v° x —J / C x-An, NN HN^O / |FyV N" VANX v / = / \ XyoN / FTR130WSGR Docket No. 66412-753.601Ex. Structure131 o HN— f ° O=( / I I -A F _1N OA FId 13'X / 'A — x x Nz Z HN^ xO / »V|\ \OO -n -n n -n== I / 0N^VNX / =\ XN / AAX Mo t / yo132 \( °= ( zx.A AX A x x.o o i X 9;s ■ / ArZ / o-HX HX°T° 7 n- U_O ' z u_^ z V Y "133 O Fz XiOr\ X >\ / zIZT1 A? T ‘ r?ri ox v A YAoAi ° 7L°’F / IZHNY | z1 ° r A \ CN~O 'AN / / L‘‘'( / (R-)O \ o N< Kr\ o / fj V Q=\ >o XN>0As ° °Fci H ZA ^^ 0 134 \ )\ ° °=^ Cx(( o O LJ_ l / U_ LJ_ l / U_^=I CI CXX Z Z I T135136WSGR Docket No. 66412-753.601Ex. Structure137I I)XZ# \ / V\ / \o -n= _\^ o=Z~-_138 \^ o= o HN0 F 4 Zx^ —0 O= / V \HINA6 V rj / AX.,s / , > N O / XK N1 0'7 $x / X— N o HN.. O / | N\^ ° r / ° 1 z / ^J. Z xZIX C-i U.YCt / >° z<^ °Z_139 oV C o Zz^ HN-V O F O1=< \ °Z ^ X ""\ ° \i? r- \ o? L ^\3 / / H NAYAoAoIZ ’ IA V / S 1 ZSA> N rH / / A> CJ, N1 0'7 A / N o HN^O / V A <s> ^ |T / Y CN0N"KVNX / =\ J>7< J z ^LNXt / zy~< Zv^ y6o \ / o \ / ==140, CH M(( o O LJ_ l / U_ U- U-==CI I TIX CX z z141142WSGR Docket No. 66412-753.601Ex. Structure143 / I M IZ z\ ^O ■n=o=144 \( ° o o / \= HN—fX zA.-... X fj5o HN.,0 9"(^ 1S2 >. F NT / 0z 1 ZI N^VNX / =\ XN / OZoz- - / \ U_ 145 X C o-n< 9] - °ypA*iv z J z.p •'i" o 0i ~146 O F z>^ ^F)\ o=H2N'^V\O / x J^ NAJ }TI o-CN^VNHoZ( O LJ_=CM zI r / 0N<:SrN\ / =\ J^N / AzzO i ^o147148 OHNX'A r^TYPH^O?"<^ |I / 0N^VNX / =\ XNX / VJ^ / vJ^ yoWSGR Docket No. 66412-753.601Ex. Structure149X 13Xz">o=150 \^ o=(Zs’A A.O o 1 \ z z\ < Xzz^' ftj Q ftoo V°\- A 151 o FA A z 1. Z’\ H2N n _ _ v ftz\==o ^^ft TXZ“■ JJR> r L U / yAX Clr-n / / X-NH ftft °”HN.,0 9"(^ / o \\°oz-^^F1 / ° oAA A^ Z Z^ \ X \N<irN\ / =\A / xH / ftft u-oz-- ^ / ^n / O yofttftJ A] t [xA o-^FCN152 N^s\1 JL / fzz XxsS'f~ ^ ^'AirNt i 7$ n)\ % o \ / °==zXS ^A JANO4JO \ / =(( O o LJ_==I CI CXX AftA z zz HJX z / X \-xft:NAH 0153154WSGR Docket No. 66412-753.601Ex. Structure155 0NH2 0I jio,°o 4iI)Xz\O -n=\Y o= H 0156 Y z^o o I \ z \ z\\ O < \ z\ Yz~~z^ / x °Z- \ jozo V V^X?^g VoA 157 X C-n / >oz- ' 'YX Ok X o / z _ o. / X z z'-;'=^' \1\o jj [ [| 2^?: Tf^^ y^ b b bY7zxz~~ / 158z^ ^ ^^L)\ )\ o \ o o / ===H((( O O O LJ_ LJ_ u-^==CM CMM C z z zI T T159160 0 FH'x° HN^.0..< ■ < O,N<^Y^N\ / =\ \~oN\ _ A^O v^ y< VyO / x^F\FO=X 1H OWSGR Docket No. 66412-753.601Ex. Structure161X N>z\O T1=kA\p o=162 0 o HlNH20 A0 / HXz7 u_°^■i?< A Y °V1 I1 Z—IZ T1H 0t •163 / ==] O FA Z ^, <4,HN., o \l0= plHnPrP PAN\ _( O u-= p-r zx ozA V-xF J(R) \ok Jz NAH 01164 / ^=1 0 FpTOXNAX F o0165166 / ===! 0—NJ IIN'^N'PP]Hn1 II pF l1^ JNN5L, F HN.. O / O^\ \--J / / rX \| / ===< / ° Ar \ \ / NA\ \, Z" NH 1 ' \ X / / \(R) VNITN\ PA ZAO \ VV^O tJX w ytF0WSGR Docket No. 66412-753.601Ex. Structure167I I M N>z z\ )ooTl==y kAo ^z.-- 168 \^ o=4 ( -Z ZKK^o y A^ ' J i ZYJ JM OA1 AA< & - Aoz- / \K X-nCN 0i ' zZ^1ftO169 / =! 0 F\ ) o= °l / \,fA XZ^o THO \o=T / \FO H ZIHz AYAY \— / VNX7 1 z o1 0171 0HN A0J > N I / ^ y'N\A H^O A00WSGR Docket No. 66412-753.601Ex. Structure172T NJzV X i Vyo -n- \ / / (\ 7 \= _yy o173yy o0 Avzo ofl oz- tf aA ■.1 zy 7^y A / Aoo M °QZ£~ » / ' iz O o Q CK f' 174y A\ ) o=y [f'ZzAx( ^ O u-=Io \l=AI zxzZliz- 175■v HN^ xO / _ O,^< X / -< p-iN^N\ A\ )"oNv-xq / / V-XfM1> A 7N HA 0176WSGR Docket No. 66412-753.601Ex. Structure177 0HN^F\ 'vF— N 3 II / \N-^N^ Y^ \ 7FY'NAHN^O0N^ ify^yJ^o\— / yNxO178 — N / = Jn J 0IN^N'-' VY _H 1 I] OF' J^ — F0179N'N / . OH / > HN-V(W )(Zr o ZVVT > ^'N\J ^N'NCK. NH / fsjX / 11 / °NITN^V=V^'N / 180 / O / HNYH1 F0=k >[ |Ti V^° / \— 4. / / vI^ F / X^’N / , NO^NH N1 / °N< J=FN\ / =\ AN / 181 / =J O F'N- NA-^N / ^IZ / xJ rvoH] YVZRI r lx l| / / )^F-^V A^-Nx J HNHHN^O _F\— / yNx0WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601Ex. Structure187 0T / \FO H Art^A-rt \— / yNxo188o 1 ZI oy □_x> \ x\ yg / 189 VogXrtA - o 0 QJX1900 F6 j,F^V)ZA )\'~V / °=,-rtrt<vy° y )\ o= 0A( O u.= / ZIZ\— / y-Nx01910 F7 r"\T. / A^'N-X / VA o HN, rtD ^j°"(sy^ / NA-yy \—A / ^ VoNXo192 o FHAxJ / x / NAO^CyN^ \ — / JT F VNHHN^O0NA-yyyAo0WSGR Docket No. 66412-753.601Ex. Structure193I MzVo ■nX M\^ o=194 O FFHM / x VNVTrHT oVN^ F OHN~Y> O ^X XoNVAO K A° Oz- I — / XXX \— / VNU. \Xz0195 / =1 O FFNNVNA^*\ iz m xy^yohL J. fAiA x rNHoV^ / N^XXFo HN.,0 / _ / NVWA / OXvM \— / yNx0196 oHN-Xn,-K.rXV-V / XA -hTV Vy ^NHrl^o P'VXX?NVTN\ XX VNX197 / X o FA A A XXoHL J PNX J / )TNHfT""^ OX / N'X ^^F OZHNK -> OAxA-X \— / \< NXoz198 0 F" AoWSGR Docket No. 66412-753.601Ex. Structure199 0 FHLO YtNk T / \FO H NVV O / O\— / VNXo200 o HN— / o o=< \HN^O 1*\— / \-NX0201 0 F'ZO" T" 7CN^Ny / A >o \F> N^°O202 OHN-y-v...c-c- y FHN^.0 / w|| / —0N<TTN\ / =\ / ^N / AA / iJ yo203H0= / \F\ ysiy£Ao FMz FHN^O ^J°".(.srr^P ^PrNy. r\ Pp\— / \< NXoWSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601Ex. Structure209 O FFHN^O ' / IZ\O ■n= AVO / ?\— / VNX\4 °= 0210 4ZK, 0° / \4v HN^( rj }JK R cQv iF0b J- < ■N^OYY° n| [O z-HN.,0; Cb^ ■nT "” °\ AWA / O / iz\— / \-NXo o 211212 o HN— / 0 F 0= / \HN^O N\— / VNX02131— NFo^ / N^NH 0WSGR Docket No. 66412-753.601Ex. Structure214 / =1 O FFN'N^N-^\AA A A QNHHN.,0FA KA^AA \^— / / AN'X0215 0HNA OA< AF. 7O F / VN"=J-oHN^ / O;NVAA > OAA7\— / VNXo'216 F O\ HA o -< A&"HN^ / ,0 3AVO A? / AAA \— / yNx0217,°AANAM H A 0218 O F FhLj ACNJU rNHHN 1^ / O OXNA / F0 / AAA \— / VNX0219 °F_,\ NA A A / -. r A A / A ' o H / IL JJFT F oHNy°NA-y ry yoAAA \— / ANX0WSGR Docket No. 66412-753.601Ex. Structure220FAJ HN1.,0 o / A V-7 / F01z I / 0N<krN\ / =\ JLN / pzIZ221 \O -n= 0HNAx° / \ Fz-°Yr I IO Z- HN^ ^O 3[ / —0NATN\ / =\ JLN / XJL / t / y222 FF ° J A\=OHN^ ^O;Awy / oAA / \— / yNxo223 oF\\ A A / AO H XJ]. ZNXf rNHF"HYNFy°0NA-N\ Fy yo / X-FF \— / yNxo2241— NxXVFF J< F\ oA / N" AH OWSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601Ex. Structure230 / N'N 0F HN' j^j / HNA 21 I Mz zO^ Vo ■npz, NH 11 / 0V \ OOz n= Z\ \^' # \ o _ v= V ¥°231 n *z v ' ' z —.\ 1A 7 0?t "X A ° < -,0 H AxO Z-z / ¥ o■ V ° / ^Zz^1\ \ o 232233 ° F FHN^.0NATN\ ZA VO / ZZZ \— / y-Nx0234 o FNHF L ir J nJ AN / N^Xy A / / X)'rN / HHN^O — / F\— / VNX0WSGR Docket No. 66412-753.601Ex. Structure235HnF 1 1 Tex / =! 0 F / " NF / \ (\J 7 \= _( ) ° "='X5o-cX C zK. NH 3 / Y rjWA / 0Y / Y \— / ^2. 0236 iY°y 'Yoz-z\f o9\Y*<z z 1 zx""x>237 oHN^YN° > NX- YHli O / 0NITNVV=V^ / 00238 / =n O F■ Y x.°YNHY J-N° N-iH 0239 0,FJL ^=\ r Yo H j rVNAJ rNHFY " A rNA-N\ Yy yoYxY-X \— / VNX0WSGR Docket No. 66412-753.601Ex. Structure240 o HN— / 0 / S5SA> NHlAo 1 V y- 1 / \ / \ / ( \= _ / 0N<krNx / =\ XN° \ / / z,2410 A zJ AZ oy" A^ ZrS ° Z YX *o z- M AZZ° \Z Z- A11 z X / oH“242 0o HNyo \-F\ 'y ozZ ^vF / ==n 0 (j Si—N\ II\ oZ^ \ \\ 1tyZ. u-— ’w AH1AS rOA( MiV F Arc\§^0O^NHy cHN<V\H\f—y / A y-~? Nxo243WSGR Docket No. 66412-753.601Ex. Structure244 0HNAF.1 i z z p- pp / z z==1 O FFIZ IZ \ \oo -n -n==y K,O^Nx xH°° / \ \ / 4 y z Zx^ 3^AA? J \.— / y-Nx6 0 o / = Z <Z‘" T 245! O F / x F0O 7Z-- / v aA6 HN. UD ry fA AA / w \—y / z / \ Vy <?,°-oNXO / \^5 ° / ^\rz z^01\\z z^ 6 9 o1V 246 o 9 °yz ^^y\ °^H\ZIo=247 1 9 oHN— ( / X HN^’|O / © -m Fy |A NAyTN / X / =\0t / yAoN / 248249WSGR Docket No. 66412-753.601Ex. Structure2501 zpzTZ\ V ^ °oz=251S" Xo A ° \\ xz / zz^_zo <^252 / =i O F F _ _ —N. A. Ji _ / J"'^\=zON" Tj A z / / > oz- A rNHHN.,0WyoA o / Xa / Ay \_ / VNXooA253 — N n 7 A%=°N 9x)F A o oZ " H JI \ Y HN^O O / X-O7F Oz1 / AJA / \— / VNX0254 oHN-XF01 O'" Z\ "N< / \xA—J-Q XN HN. ^0 / |r / 0N^VN\ / =\ JLN / zXX o y°255 o F F^N- N AA AHAA i A / L J y. ZNX / VT ^NHoXNZ HN^O F 6AJM^= / oyN-WSGR Docket No. 66412-753.601Ex. Structure256 / =1 O'NFN A^NH' IY / LXX - J / FJ. PA f XT F ONHHN.,0Ay / w0257 oF.67 1"^ Z>"NX. / XXO"'\ / / x—HN^ON|nr / ii^jN\ / / =\0XN X L t / y6X258 — N / == \1 o II F I~N" |A °TX x A " A A^^A 0^259 Z==l 0FA XHX U r _^ X Xx-X r^v x ro / / X^NHFHTN^O O-O-ND H orAJMx=ryNxo260 / => 0 FFHN^ON^ry xyAoo261 oHN-X»x xAXX HyN. ^0 / O'X‘‘O w |N A r \ / / =\0ANXA JJA vA voWSGR Docket No. 66412-753.601Ex. Structure262 / N'N oJI J HN-JHN 0=6 \O^. NH / |1 / 0NAT\ / =\ AN / A AA AU263 / N'N oJI / / HN— JF I HNT 0=6F. \A \o r Oi NT o z. AA / A \L <z-" 1 O'' \ / x— NO^NH / w|1 / NATN\ / =\ J0LN / / A N AA —AA J264 FA °FJ T' - A. AA° "'N“ VO^. NH a o;fVi Oi ir" 7, x oA j A □ oA.ZI \JLZ'='JAo265 z rt1266 / =1 O FFaXjiHN^OFA ANAAyA / =yT / A? NX0267 o FaA n-oAA HN^OFN^AAfA A? ANAAA= / A oA-WSGR Docket No. 66412-753.601Ex. Structure268i zpz0Z I IZ IZS \o -n)O -n9 °==26=x x°° / \ / \ -Z.U Y6 Y270 0 P Y 70-xoV\ iz_ 1 zX / z“ X C-noJ C ° / ^\rz z z / ^ _1zz1\ u^ \1o V o °z~Xo c\Yrz" ' 271 Q IM "-\ )\ °=272 / =N O F F0OX"^ r ° HN^O / YU-Z \— / \-NxO273 0 O.HuH2NM / / l'N rr / CY^0HN^O?" FNlTN\ / =\^Y t / yoWSGR Docket No. 66412-753.601

[0249] In some embodiments the compound disclosed herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, is selected from the group consisting of:WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601

[0250] In some embodiments the compound disclosed herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, is selected from the group consisting of:WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601

[0251] In some embodiments the compound disclosed herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, is selected from the group consisting of:WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601

[0252] In some embodiments the compound disclosed herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, is selected from the group consisting of:WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601

[0253] In some embodiments the compound disclosed herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, is selected from the group consisting of:WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601

[0254] In some embodiments the compound disclosed herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, is selected from the group consisting of:WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601

[0255] In some embodiments the compound disclosed herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, is selected from the group consisting of:WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601

[0256] In some embodiments the compound disclosed herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, is selected from the group consisting of:WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601WSGR Docket No. 66412-753.601Further Forms of Compounds Disclosed HereinIsomers / Stereoisomers

[0257] In some embodiments, the compounds described herein exist as geometric isomers. In some embodiments, the compounds described herein possess one or more double bonds. The compounds presented herein include all cis, trans, syn, anti, entgegen (E), and zusammen (Z) isomers as well as the corresponding mixtures thereof. In some situations, the compounds described herein possess one or more chiral centers and each center independently exists in the R configuration or S configuration. The compounds described herein include all diastereomeric, enantiomeric, and epimeric forms as well as the corresponding mixtures thereof. In additional embodiments of the compounds and methods provided herein, mixtures of enantiomers and / or diastereoisomers, resulting from a single preparative step, combination, or interconversion are useful for the applications described herein. In some embodiments, the compounds described herein are prepared as their individual stereoisomers by reacting a racemic mixture of the compound with an optically active resolving agent to form a pair of diastereoisomeric compounds, separating the diastereomers and recovering the optically pure enantiomers. In some embodiments, dissociable complexes are preferred. In some embodiments, the diastereomers have distinct physical properties (e.g., melting points, boiling points, solubilities, reactivity, etc.) and are separated by taking advantage of these dissimilarities. In some embodiments, the diastereomers are separated by chiral chromatography, or preferably, by separation / resolution techniques based upon differences in solubility. In some embodiments, the optically pure enantiomer is then recovered, along with the resolving agent, by any practical means that would not result in racemization.Labeled compounds

[0258] In some embodiments, the compounds described herein exist in their isotopically-labeled forms. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such isotopically-labeled compounds. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such isotopically-labeled compounds asWSGR Docket No. 66412-753.601pharmaceutical compositions. Thus, in some embodiments, the compounds disclosed herein include isotopically-labeled compounds, which are identical to those recited herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into compounds disclosed herein include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, and chlorine, such as2H,3H,13C,14C,15N,18O,170,31P,32P,35S,18F, and36C1, respectively. Compounds described herein, and the pharmaceutically acceptable salts, solvates, or stereoisomers thereof which contain the aforementioned isotopes and / or other isotopes of other atoms are within the scope of this invention. Certain isotopically-labeled compounds, for example those into which radioactive isotopes, such as3H and14C, are incorporated, are useful in drug and / or substrate tissue distribution assays. Tritiated, i.e.,3H and carbon-14, i.e.,14C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavy isotopes, such as deuterium, i.e.,2H, produces certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements. In some embodiments, one or more hydrogen in a compound disclosed herein has been replaced by a deuterium atom. In some embodiments, one or more alkyl substituents in a compound disclosed herein has been replaced by a deuteroalkyl substituents. In some embodiments, one or more -CH3 in a compound disclosed herein has been replaced by a -CDs.

[0259] In some embodiments, the compounds described herein are labeled by other means, including, but not limited to, the use of chromophores or fluorescent moieties, bioluminescent labels, or chemiluminescent labels.Pharmaceutically acceptable salts

[0260] In some embodiments, the compounds described herein exist as their pharmaceutically acceptable salts. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such pharmaceutically acceptable salts. In some embodiments, the methods disclosed herein include methods of treating diseases by administering such pharmaceutically acceptable salts as pharmaceutical compositions.

[0261] In some embodiments, the compounds described herein possess acidic or basic groups and therefore react with any of a number of inorganic or organic bases, and inorganic and organic acids, to form a pharmaceutically acceptable salt. In some embodiments, these salts are prepared in situ during the final isolation and purification of the compounds disclosed herein, or a solvate, or stereoisomer thereof, or by separately reacting a purified compound in its free form with a suitable acid or base, and isolating the salt thus formed.

[0262] Examples of pharmaceutically acceptable salts include those salts prepared by reaction of the compounds described herein with a mineral, organic acid or inorganic base, such salts including, but not limited to, acetate, acrylate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, bisulfite, bromide, butyrate, butyn-l,4-dioate, camphorate, camphorsulfonate, caproate, caprylate, chlorobenzoate, chloride, citrate, cyclopentanepropionate, decanoate, digluconate, gluconate, dihydrogenphosphate, dinitrobenzoate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptanoate, glycerophosphate,WSGR Docket No. 66412-753.601glycolate, hemisulfate, heptanoate, hexanoate, hexyne- 1,6-dioate, hydroxybenzoate, y-hydroxybutyrate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, iodide, isobutyrate, lactate, maleate, malonate, methanesulfonate, mandelate metaphosphate, methoxybenzoate, methylbenzoate, monohydrogenphosphate, 1-napthalenesulfonate, 2-napthalenesulfonate, nicotinate, nitrate, palmoate, pectinate, persulfate, 3 -phenylpropionate, phosphate, picrate, pivalate, propionate, pyrosulfate, pyrophosphate, propiolate, phthalate, phenylacetate, phenylbutyrate, propanesulfonate, salicylate, succinate, sulfate, sulfite, succinate, suberate, sebacate, sulfonate, tartrate, thiocyanate, tosylate, undecanoate, and xylenesulfonate.

[0263] Further, the compounds described herein can be prepared as pharmaceutically acceptable salts formed by reacting the free base form of the compound with a pharmaceutically acceptable inorganic or organic acid, including, but not limited to, inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid metaphosphoric acid, and the like; and organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, p -toluene sulfonic acid, tartaric acid, trifluoroacetic acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, arylsulfonic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzene sulfonic acid, 2 -naphthalene sulfonic acid, 4-methylbicyclo-[2.2.2]oct-2-ene-l-carboxylic acid, glucoheptonic acid, 4,4 ’-methylenebis-(3 -hydroxy-2 -ene-1 -carboxylic acid), 3 -phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid and muconic acid. In some embodiments, other acids, such as oxalic, while not in themselves pharmaceutically acceptable, are employed in the preparation of salts useful as intermediates in obtaining the compounds disclosed herein, solvate, or stereoisomer thereof and their pharmaceutically acceptable acid addition salts.

[0264] In some embodiments, those compounds described herein which comprise a free acid group react with a suitable base, such as the hydroxide, carbonate, bicarbonate, sulfate, of a pharmaceutically acceptable metal cation, with ammonia, or with a pharmaceutically acceptable organic primary, secondary, tertiary, or quaternary amine. Representative salts include the alkali or alkaline earth salts, like lithium, sodium, potassium, calcium, and magnesium, and aluminum salts and the like. Illustrative examples of bases include sodium hydroxide, potassium hydroxide, choline hydroxide, sodium carbonate, N+(C1.C4alkyl)4hydroxide, and the like.

[0265] Representative organic amines useful for the formation of base addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine and the like. It should be understood that the compounds described herein also include the quatemization of any basic nitrogencontaining groups they contain. In some embodiments, water or oil-soluble or dispersible products are obtained by such quatemization.SolvatesWSGR Docket No. 66412-753.601

[0266] In some embodiments, the compounds described herein exist as solvates. The invention provides for methods of treating diseases by administering such solvates. The invention further provides for methods of treating diseases by administering such solvates as pharmaceutical compositions.

[0267] Solvates contain either stoichiometric or non-stoichiometric amounts of a solvent, and, in some embodiments, are formed with pharmaceutically acceptable solvents, such as water, ethanol, and the like. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. Solvates of the compounds described herein can be conveniently prepared or formed during the processes described herein. By way of example only, hydrates of the compounds described herein can be conveniently prepared from an aqueous / organic solvent mixture, using organic solvents including, but not limited to, dioxane, tetrahydrofuran or methanol. In addition, the compounds provided herein can exist in unsolvated as well as solvated forms. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the compounds and methods provided herein.Method of Treatment

[0268] Disclosed herein are methods of modulating STAT6 activity in a subject, comprising administering to the subject a compound described herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

[0269] In some embodiments, the disorder responsive to the modulation (e.g., degradation) of STAT6 include, but is not limited to, allergic disorder, atherosclerosis, autoimmune diseases such as lupus and rheumatoid arthritis, autoinflammatory syndromes, cancer, cardiovascular disorder, CNS disorder, condition associated with cell death, conditions associated with organ transplantation, destructive bone disorder, diabetes, gout and gouty arthritis, hereditary disorder, hormone -related disease, immunodeficiency disorder, infectious disease, inflammatory bowel disease, inflammatory disorder, liver disease, metabolic disorder, neurodegenerative disorder, neurological disorder, osteoarthritis, pathologic immune conditions involving T cell activation, proliferative disorder, psoriasis, thrombin-induced platelet aggregation, viral disease, and Waldenstrom’s Macroglobulinemia.

[0270] Proliferative disorders, include, but are not limited to a benign or malignant tumor, solid tumor, liquid tumor, carcinoma of the brain, kidney, liver, adrenal gland, bladder, breast, stomach, gastric tumors, ovaries, colon, rectum, prostate, pancreas, lung, vagina, cervix, testis, genitourinary tract, esophagus, larynx, skin, bone or thyroid, sarcoma, glioblastomas, neuroblastomas, multiple myeloma, gastrointestinal cancer, especially colon carcinoma or colorectal adenoma, a tumor of the neck and head, an epidermal hyperproliferation, psoriasis, prostate hyperplasia, a neoplasia, a neoplasia of epithelial character, adenoma, adenocarcinoma, keratoacanthoma, epidermoid carcinoma, large cell carcinoma, non-small-cell lung carcinoma, lymphomas (Hodgkin and non-Hodgkin), a mammary carcinoma, follicular carcinoma, undifferentiated carcinoma, papillary carcinoma, seminoma, melanoma, an IL-I driven disorder, an MyD88 driven disorder, smoldering of indolent multiple myeloma, or hematological malignancies (including leukemia, diffuse large B-cell lymphoma (DLBCL), ABC DLBCL, chronic lymphocytic leukemia (CLL), chronic lymphocytic lymphoma, primary effusion lymphoma, BurkittWSGR Docket No. 66412-753.601lymphoma / leukemia, acute lymphocytic leukemia, B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenstrom’s macroglobulinemia (WM), splenic marginal zone lymphoma, multiple myeloma, plasmacytoma, intravascular large B-cell lymphoma).

[0271] In some embodiments, the cancer is selected from glioma, breast cancer, prostate cancer, head and neck squamous cell carcinoma, skin melanomas, ovarian cancer, malignant peripheral nerve sheath tumors (MPNST), and pancreatic cancer. In other embodiments, the cancer to be treated is cancer selected from glioma, breast cancer, prostate cancer, head and neck squamous cell carcinoma, skin melanomas, ovarian cancer, malignant peripheral nerve sheath tumors (MPNST), pancreatic cancer, nonsmall cell lung cancer (NSCLC) including EGFR-mutantNSCLC, urothelial cancer, liver cancer, bile duct cancer, kidney cancer, colon cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumors, and hematological malignancies include lymphomas, leukemias, myelomas, myeloproliferative neoplasms and myelodysplastic syndromes.

[0272] In some embodiments, the cancer is solid tumors (e.g., prostate cancer, renal cancer, hepatic cancer, pancreatic cancer, gastric cancer, breast cancer, lung cancer, cancers of the head and neck, thyroid cancer, glioblastoma, Kaposi's sarcoma, Castleman's disease, uterine leiomyosarcoma, melanoma etc.), hematological cancers (e.g., lymphoma, leukemia Such as acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML) or multiple myeloma), and skin cancer such as cutaneous T-cell lymphoma (CTCL), or cutaneous B-cell lymphoma.

[0273] treatment of inflammatory or obstructive airways diseases, resulting, for example, in reduction of tissue damage, airways inflammation, bronchial hyperreactivity, remodeling or disease progression. Inflammatory or obstructive airways diseases include asthma of whatever type or genesis including both intrinsic (non-allergic) asthma and extrinsic (allergic) asthma, mild asthma, moderate asthma, severe asthma, asthmatic bronchitis, exercise-induced asthma, occupational asthma, and asthma induced following bacterial infection. Treatment of asthma is also to be understood as embracing treatment of subjects, e.g., of less than 4 or 5 years of age, exhibiting wheezing symptoms and diagnosed or diagnosable “as "wheezy infants", an established patient category of major medical concern and now often identified as incipient or early -phase asthmatics.

[0274] In some embodiments, the disorder responsive to the modulation (e.g., degradation) of STAT6 is autoimmune diseases including, but are not limited to, graft versus host disease, transplantation, transfusion, anaphylaxis, allergies (e.g., allergies to plant pollens, latex, drugs, foods, insect poisons, animal hair, animal dander, dust mites, or cockroach calyx), type I hypersensitivity, allergic conjunctivitis, allergic rhinitis, and atopic dermatitis.

[0275] In some embodiments, the disorder responsive to the modulation (e.g., degradation) of STAT6 is other inflammatory or obstructive airways diseases and conditions to which the present invention is applicable and include acute lung injury (ALI), adult / acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary, airways or lung disease (COPD, COAD or COLD), including chronic bronchitis or dyspnea associated therewith, emphysema, as well as exacerbation of airways hyperreactivity consequent to other drug therapy, in particular other inhaled drug therapy. Compounds,WSGR Docket No. 66412-753.601salts, and compositions described herein are also useful in the treatment of bronchitis including, but not limited to, acute, arachidic, catarrhal, croupous, chronic orphthinoid bronchitis. Compounds, salts, and compositions described herein are also useful in the treatment of pneumoconiosis (an inflammatory, commonly occupational, disease of the lungs, frequently accompanied by airways obstruction, whether chronic or acute, and occasioned by repeated inhalation of dusts) of whatever type or genesis, including, for example, aluminosis, anthracosis, asbestosis, chalicosis, ptilosis, siderosis, silicosis, tabacosis and byssinosis.

[0276] In some embodiments, the disorder responsive to the modulation (e.g., degradation) of STAT6 is inflammatory or allergic conditions of the skin, for example psoriasis, contact dermatitis, atopic dermatitis, alopecia areata, erythema multiforma, dermatitis herpetiformis, scleroderma, vitiligo, hypersensitivity angiitis, urticaria, bullous pemphigoid, lupus erythematosus, systemic lupus erythematosus, pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus, epidermolysis bullosa acquisita (EBA), acne vulgaris, and other inflammatory or allergic conditions of the skin.

[0277] In some embodiments, the disorder responsive to the modulation (e.g., degradation) of STAT6 is a disorder having an inflammatory component, for example, treatment of diseases and conditions of the eye such as ocular allergy, conjunctivitis, keratoconjunctivitis sicca, and vernal conjunctivitis, diseases affecting the nose including allergic rhinitis, and inflammatory disease in which autoimmune reactions are implicated or having an autoimmune component or etiology, including autoimmune hematological disorders (e.g. hemolytic anemia, aplastic anemia, pure red cell anemia and idiopathic thrombocytopenia), systemic lupus erythematosus, rheumatoid arthritis, polychondritis, scleroderma, Wegener granulomatosis, dermatomyositis, chronic active hepatitis, myasthenia gravis, Steven-Johnson syndrome, idiopathic sprue, autoimmune inflammatory bowel disease (e.g. ulcerative colitis and Crohn's disease), irritable bowel syndrome, celiac disease, periodontitis, hyaline membrane disease, kidney disease, glomerular disease, alcoholic liver disease, multiple sclerosis, endocrine ophthalmopathy, Grave's disease, sarcoidosis, alveolitis, chronic hypersensitivity pneumonitis, multiple sclerosis, primary biliary cirrhosis, uveitis (anterior and posterior), Sjogren’s syndrome, keratoconjunctivitis sicca and vernal keratoconjunctivitis, interstitial lung fibrosis, psoriatic arthritis, systemic juvenile idiopathic arthritis, cryopyrin-associated periodic syndrome, nephritis, vasculitis, diverticulitis, interstitial cystitis, glomerulonephritis (with and without nephrotic syndrome, e.g. including idiopathic nephrotic syndrome or minal change nephropathy), chronic granulomatous disease, endometriosis, leptospirosis renal disease, glaucoma, retinal disease, ageing, headache, pain, complex regional pain syndrome, cardiac hypertrophy, muscle wasting, catabolic disorders, obesity, fetal growth retardation, hypercholesterolemia, heart disease, chronic heart failure, mesothelioma, anhidrotic ectodermal dysplasia, Behcet’s disease, incontinentia pigmenti, Paget’s disease, pancreatitis, hereditary periodic fever syndrome, asthma (allergic and non-allergic, mild, moderate, severe, bronchitis, and exercise-induced), acute lung injury, acute respiratory distress syndrome, eosinophilia, hypersensitivities, anaphylaxis, nasal sinusitis, ocular allergy, silica induced diseases, COPD (reduction of damage, airways inflammation, bronchial hyperreactivity, remodeling or disease progression), pulmonary disease, cystic fibrosis, acid induced lung injury,WSGR Docket No. 66412-753.601pulmonary hypertension, polyneuropathy, cataracts, muscle inflammation in conjunction with systemic sclerosis, inclusion body myositis, myasthenia gravis, thyroiditis, Addison’s disease, lichen planus, Type 1 diabetes, or Type 2 diabetes, appendicitis, atopic dermatitis, asthma, allergy, blepharitis, bronchiolitis, bronchitis, bursitis, cervicitis, cholangitis, cholecystitis, chronic graft rejection, colitis, conjunctivitis, Crohn’s disease, cystitis, dacryoadenitis, dermatitis, dermatomyositis, encephalitis, encephalomyelitis, endocarditis, endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibrositis, gastritis, gastroenteritis, Henoch-Schonlein purpura, hepatitis, hidradenitis suppurativa, immunoglobulin A nephropathy, interstitial lung disease, laryngitis, mastitis, meningitis, myelitis myocarditis, myositis, nephritis, oophoritis, orchitis, osteitis, otitis, pancreatitis, parotitis, pericarditis, peritonitis, pharyngitis, pleuritis, phlebitis, pneumonitis, pneumonia, polymyositis, proctitis, prostatitis, pyelonephritis, rhinitis, salpingitis, sinusitis, stomatitis, synovitis, tendonitis, tonsillitis, ulcerative colitis, uveitis, vaginitis, vasculitis, or vulvitis.

[0278] In some embodiments, the disorder responsive to the modulation (e.g., degradation) of STAT6 is cardiovascular diseases including, but are not limited to, restenosis, cardiomegaly, atherosclerosis, myocardial infarction, ischemic stroke, congestive heart failure, angina pectoris, reocclusion after angioplasty, restenosis after angioplasty, reocclusion after aortocoronary bypass, restenosis after aortocoronary bypass, stroke, transitory ischemia, a peripheral arterial occlusive disorder, pulmonary embolism, and deep venous thrombosis.

[0279] In some embodiments, the disorder responsive to the modulation (e.g., degradation) of STAT6 is a neurodegenerative disease including, but are not limited to, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, cerebral ischemia, and neurodegenerative disease caused by traumatic injury, glutamate neurotoxicity, hypoxia, epilepsy, treatment of diabetes, metabolic syndrome, obesity, organ transplantation and graft versus host disease.

[0280] In some embodiments, the disorder responsive to the modulation (e.g., degradation) of STAT6 is alopecia, aspergillus, asthma, atomic dermatitis, chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis with nasal polyposis, gastritis, inflammatory bowel disease, pemphigoid, prurigo nodularis, sinusitis, or urticaria.Dosing

[0281] In certain embodiments, the compositions containing the compound(s) described herein are administered for therapeutic treatments. In certain therapeutic applications, the compositions are administered to a patient already suffering from a disease or condition, in an amount sufficient to cure or at least partially arrest at least one of the symptoms of the disease or condition. Amounts effective for this use depend on the severity and course of the disease or condition, previous therapy, the patient’s health status, weight, and response to the drugs, and the judgment of the treating physician. Therapeutically effective amounts are optionally determined by methods including, but not limited to, a dose-escalation.WSGR Docket No. 66412-753.601Routes of Administration

[0282] Suitable routes of administration include, but are not limited to, oral, intravenous, rectal, aerosol, parenteral, ophthalmic, pulmonary, transmucosal, transdermal, vaginal, otic, nasal, and topical administration. In addition, by way of example only, parenteral delivery includes intramuscular, subcutaneous, intravenous, intramedullary injections, as well as intrathecal, direct intraventricular, intraperitoneal, intralymphatic, and intranasal injections.Pharmaceutical Compositions / Formulations

[0283] The compounds described herein are administered to a subject in need thereof, either alone or in combination with pharmaceutically acceptable carriers, excipients, or diluents, in a pharmaceutical composition, according to standard pharmaceutical practice. In some embodiments, the compounds described herein are administered to animals.

[0284] In another aspect, provided herein are pharmaceutical compositions comprising a compound described herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, and at least one pharmaceutically acceptable excipient. Pharmaceutical compositions are formulated in a conventional manner using one or more pharmaceutically acceptable excipients that facilitate processing of the active compounds into preparations that can be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen. A summary of pharmaceutical compositions described herein can be found, for example, in Remington: The Science and Practice of Pharmacy, Nineteenth Ed (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington’s Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, H. A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N. Y., 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams & Wilkins 1999), herein incorporated by reference for such disclosure.Combination

[0285] Disclosed herein are methods of treating a disease or disorder associated with STAT6 using a compound disclosed herein, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, in combination with an additional therapeutic agent.

[0286] In some embodiments, the additional therapeutic agent is administered at the same time as the compound disclosed herein. In some embodiments, the additional therapeutic agent and the compound disclosed herein are administered sequentially. In some embodiments, the additional therapeutic agent is administered less frequently than the compound disclosed herein. In some embodiments, the additional therapeutic agent is administered more frequently than the compound disclosed herein. In some embodiments, the additional therapeutic agent is administered prior than the administration of the compound disclosed herein. In some embodiments, the additional therapeutic agent is administered after the administration of the compound disclosed herein.WSGR Docket No. 66412-753.601EXAMPLEIntermediate 1Step 1:

[0287] To a solution of 4-bromo-5 -methyl -2H-l,2-oxazol-3 -one (1.0 g, 5.61 mmol) in toluene (30 mL) was added 1,1,1 -trimethoxyethane (6.75 g, 56.2 mmol) under nitrogen atmosphere. The resulting solution was stirred at 110 °C overnight under nitrogen atmosphere. The reaction was concentrated under vacuum. The crude product was purified by flash column chromatography on C18 silica with MeCN in water (0.5% TFA) to afford 4-bromo-2,5-dimethyl-l,2-oxazol-3-one (540 mg, 50% yield) as a yellow oil. LCMS (ESI, m / z): 192.3 [M+H]+. ’HNMR(400 MHz, DMSO-d6) 53.42 (s, 3H), 2.29 (s, 3H).Step 2:

[0288] To a solution of 4-bromo-2, 5 -dimethyl- l,2-oxazol-3 -one (25.0 g, 130 mmol) and 4, 4, 5, 5-tetramethyl-2-[4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl]-l,3,2-dioxaborolane (86.0 g, 260 mmol) in Dioxane (600 mL) and H2O (150 mL) were added K2CO3 (54.0 g, 390 mmol) and Pd(dppf)Cl2-CH2Cl2 (21.0 g, 26 mmol, 0.2 equiv) under nitrogen atmosphere. The resulting mixture was stirred at 80 °C for 2 h under nitrogen atmosphere. Solids were filtered out and the solvent was evaporated under vacuum. The crude product was purified by column chromatography (petroleum ether / ethyl acetate = 1: 1) to afford 2,5-dimethyl-4-[4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl]-l,2-oxazol-3-one (27.0 g, 65.8% yield, 90% purity) as a grey solid. LCMS (ESI, m / z): 316.7 [M+H]+.1H NMR (400 MHz, CDCh) 57.86 (d, J = 7.8 Hz, 2H), 7.56 (d, J = 7.8 Hz, 2H), 3.54 (s, 3H), 2.41 (d, J = 14.3 Hz, 3H), 1.35 (s, 12H).WSGR Docket No. 66412-753.601Intermediate 2CO, TEA, Pd(dppf)CI2. CH2CI2PhSO2CI MeOH, 110°C, 3 days, 5MPa NaH, THF, O°C-rt, 2 hStep 1 Step 2Step 1:

[0289] To a solution of 7-chloro-lH-pyrrolo[2,3-c]pyridine (25.0 g, 164 mmol) in methanol (170 mL) was added Et3N (15.0 g, 247 mmol) followed by Pd(dppf)C12-CH2C12 (13.4 g, 16.4 mmol) under nitrogen atmosphere. The mixture was recharged with carbon monoxide gas three times and the resulting mixture was stirred under carbon monoxide atmospheres (50 atm) at 110 °C for 3 days. The mixture was concentrated under vacuum. The residue was purified by column chromatography (petroleum ether / ethyl acetate = 2: 1) to afford methyl lH-pyrrolo[2,3-c]pyridine-7-carboxylate (23 g, 79.7% yield) as a light yellow solid. LCMS (ESI, m / z): 177.4 [M+H]+. 'H NMR (400 MHz, CDC13) 59.98 (s, 1H), 8.50 - 8.34 (m, 1H), 7.77 (d, J = 5.2 Hz, 1H), 7.55 - 7.43 (m, 1H), 6.71 - 6.57 (m, 1H), 4.15 - 4.02 (m, 3H).Step 2:

[0290] To a solution of methyl lH-pyrrolo[2,3-c]pyridine-7-carboxylate (23 g, 130.6 mmol) in THF (230 mL) was added NaH (6.8 g, 63.3 mmol) at 0°C. The mixture was stirred at 0°C for 30 mins. Then benzenesulfonyl chloride (34.6 g, 195.8 mmol) was added. The mixture was stirred at room temperature for 2 hrs. The reaction was quenched with ice-water. The mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4. The organic layer was concentrated and purified by column chromatography (petroleum ether / ethyl acetate = 4: 1) to afford methyl 1 -(phenylsulfonyl)- 1H-pyrrolo[2,3-c]pyridine-7-carboxylate (25.8 g, 62.5% yield) as a yellow solid. LCMS (ESI, m / z): 317.5 (M+H)+. 'HNMR (400 MHz, DMSO-d6) 58.41 (d, J = 5.2 Hz, 1H), 8.16 (d, J = 3.7 Hz, 1H), 7.92 - 7.86 (m, 2H), 7.81 (d, J = 5.2 Hz, 1H), 7.73 (t, J = 7.5 Hz, 1H), 7.61 (t, J = 7.8 Hz, 2H), 7.07 (d, J = 3.7 Hz, 1H), 3.91 (s, 3H).Step 3:

[0291] To a solution of methyl l-(phenylsulfonyl)-lH-pyrrolo[2,3-c]pyridine-7 -carboxylate (25.8 g, 81.6 mmol) in THF (250 mL) was added LDA (61.2 mL, 122.3 mmol) at -78°C. The mixture was stirred at -78°C for 30 mins. Then l,2-dibromo-l,l,2,2-tetrachloroethane (40.0 g, 122.3 mmol) in THF (50 mL) was added to the above mixture. The reaction mixture was stirred at -78°C for 1 hr. The reaction was quenched with sat. NH4CI (aq.) and was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4. The organic layer was concentrated and was purified by column chromatographyWSGR Docket No. 66412-753.601(petroleum ether / ethyl acetate = 3: 1) to afford methyl 2-bromo-l-(phenylsulfonyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (14.6 g, 45.3% yield) as a yellow solid. LCMS (ESI, m / z): 394.9 (M+H)+. ’H NMR (400 MHz, CDC13) 58.45 (d, J = 4.9 Hz, 1H), 7.82 (d, J = 7.9 Hz, 2H), 7.57 (t, J = 7.3 Hz, 1H), 7.47 - 7.39 (m, 3H), 6.75 (s, 1H), 3.99 (s, 3H).Step 4:

[0292] To a solution of methyl 2-bromo-l-(phenylsulfonyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (14.6 g, 36.9 mmol) in 1,4-dioxane (300 mL) and water (30 mL) was added 2,5-dimethyl-4-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)isoxazol-3(2H)-one (17.5 g, 55.4 mmol), K2CO3 (10.2 g, 73.88 mmol) followed by Pd(dppf)C12 (6.18 g, 107 mmol). The mixture was stirred at 60 °C for 16 hrs under nitrogen atmosphere. The reaction mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4. The organic layer was concentrated and purified by column chromatography (petroleum ether / ethyl acetate = 1: 1) to afford methyl 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-c]pyridine-7-carboxylate (14.1 g, 55.3% yield) as a white solid. LCMS (ESI, m / z): 504.6 (M+H)+.1H NMR (400 MHz, CDCI3) 58.57 (t, J = 4.9 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 5.1 Hz, 1H), 7.44 (dd, J= 13.9, 7.9 Hz, 3H), 7.18 (t, J = 7.9 Hz, 2H), 7.03 (d, J = 7.5 Hz, 2H), 6.56 (s, 1H), 4.15 (d, J = 3.8 Hz, 3H), 3.59 (s, 3H), 2.48 (s, 3H).Step 5:

[0293] To a solution of methyl 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(phenylsulfonyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (14.1 g, 28.0 mmol) in DMF (140 mL) was added CsF (4.25 g, 28.0 mmol). The mixture was stirred at 60°C for 1 hr. The reaction mixture was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4. The organic layer was concentrated and purified by column chromatography (petroleum ether / ethyl acetate = 1: 1) to afford methyl 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-1H-pyrrolo[2,3-c]pyridine-7-carboxylate (6.18 g, 60.74% yield) as a yellow solid. LCMS (ESI, m / z): 364.1 (M+H)+. ’H NMR (400 MHz, DMSO-d6) 5 11.33 (d, J = 13.3 Hz, 1H), 8.29 (t, J = 8.0 Hz, 1H), 8.14 - 8.03 (m, 2H), 7.81 (d, J = 5.2 Hz, 1H), 7.73 (dd, J = 14.2, 5.7 Hz, 2H), 7.14 (t, J = 6.2 Hz, 1H), 4.02 (d, J = 3.1 Hz, 3H), 3.49 (s, 3H), 2.48 (d, J = 8.5 Hz, 3H).WSGR Docket No. 66412-753.601Intermediate 3HCI in dioxane CBr4, PPh3THFStep 2 Step 3HATU, DIEA, DMF Step 6Pd / C, H2, MeOH Step 7Step 1:

[0294] To a solution of 3-(benzyloxy)cyclobutan-l-ol (5 g, 28.05 mmol) in DMF (38 mL) was added NaH (2.81 g, 70.13 mmol, 60%) in portions at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 0.5 h under nitrogen atmosphere. To the above mixture was added 2-(2-bromoethoxy)oxane (8.80 g, 42.08 mmol) dropwise at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at room temperature 2 h under nitrogen atmosphere. The reaction mixture was quenched by water and extracted with EA (3 x 50 mL). The combined organic layers were washed with brine (3 x 50 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:1) to afford 2-(2-((ls,3s)-3-(benzyloxy)cyclobutoxy)ethoxy)tetrahydro-2H-pyran (5 g, 58.2% yield, 90% purity) as a colorless oil. LCMS (ESI, m / z): 324.2 [M+EEO].Step 2:

[0295] A solution of 2-(2-((ls,3s)-3-(benzyloxy)cyclobutoxy)ethoxy)tetrahydro-2H-pyran (5 g, 16.32 mmol) and HCI in 1,4-dioxane (4.0 M) (50 mb) in Dioxane (10 mb) was stirred at room temperature for overnight under air atmosphere. The mixture was neutralized to pH 8 with saturated NaHCOs (aq.). The resulting mixture was extracted with EtOAc (3 x 100 mb). The combined organic layers were washed with brine (2 x 100 mb), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 2-((1s,3s)-3-(benzyloxy)cyclobutoxy)ethan-1-ol (2 g, 55.1% yield) as a colorless oil. LCMS (ESI, m / z): 223.1 [M+H]+.Step 3:

[0296] To a stirred solution of 2-((ls,3s)-3-(benzyloxy)cyclobutoxy)ethan-l-ol (1 g, 4.49 mmol) and PPhs (2.36 g, 8.99 mmol) in THF (25 mL) was added tetrabromomethane (2.98 g, 8.99 mmol) inWSGR Docket No. 66412-753.601portions at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 2 h under nitrogen atmosphere. The residue was purified by silica gel column chromatography, eluted with PE / EA (5:1) to afford (((ls,3s)-3-(2-bromoethoxy)cyclobutoxy)methyl)benzene (1 g, 77.9% yield, 90% purity) as a colorless oil.Step 4:

[0297] To a stirred solution of (((ls,3s)-3-(2-bromoethoxy)cyclobutoxy)methyl)benzene (400 mg, 1.40 mmol) and methyl 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (474 mg, 1.12 mmol, 86%) in DMSO (10 mL) was added K2CO3 (581 mg, 4.20 mmol) in portions at room temperature under air atmosphere. The resulting mixture was stirred at 100 °C for 2 h under air atmosphere. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (10 mmol / L NH4HCO3), 60% to 90% gradient in 10 min; detector, UV 254 nm. This resulted in methyl l-(2-((ls,3s)-3-(benzyloxy)cyclobutoxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (350 mg, 44% yield, 90% purity) as a brown oil. LCMS (ESI, m / z): 568.3 [M+H]+.Step 5:

[0298] A solution of methyl l-(2-((ls,3s)-3-(benzyloxy)cyclobutoxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo- 2.3-dihydroisoxazol-4-yl)phenyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (260 mg, 0.46 mmol) and 2M LiOH (1.5 mb, 2.29 mmol) in THF (4 mb) was stirred at 50 °C for 2 h under air atmosphere. The mixture was acidified to pH 4 with cone. HC1. The resulting mixture was extracted with CH2CU / IP A (3: 1) (3 x 20 mb). The combined organic layers were washed with brine (2 x 20 mb), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. This resulted in l-(2-((ls,3s)-3-(benzyloxy)cyclobutoxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxylic acid (240 mg, 94.7% yield, 90% purity) as a brown solid. ECMS (ESI, m / z): 554.3 [M+H]+.Step 6:

[0299] To a stirred solution of l-(2-((ls,3s)-3-(benzyloxy)cyclobutoxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo- 2.3-dihydroisoxazol-4-yl)phenyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxylic acid (280 mg, 0.50 mmol) and 3 -aminobenzamide (103 mg, 0.76 mmol) in DMF (4 mL) were added DIEA (196 mg, 1.51 mmol) and HATU (288 mg, 0.76 mmol) in portions at room temperature under air atmosphere. The resulting mixture was stirred at room temperature for 2 h under air atmosphere. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (10 mmol / L NH4HCO3), 40% to 70% gradient in 10 min; detector, UV 254 nm. This resulted in l-(2-((ls,3s)-3-(benzyloxy)cyclobutoxy)ethyl)-N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (240 mg, 70.6% yield, 90% purity) as a brown solid. ECMS (ESI, m / z): 672.3 [M+H]+.WSGR Docket No. 66412-753.601Step 7:

[0300] A solution of l-(2-((ls,3s)-3-(benzyloxy)cyclobutoxy)ethyl)-N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (240 mg, 0.35 mmol) and Pd / C (64 mg, 0.60 mmol) in methanol (10 mL) was stirred at room temperature for overnight under hydrogen atmosphere. The resulting mixture was filtered the filter cake was washed with MeOH (3 x 10 mL). The filtrate was concentrated under reduced pressure. This resulted in N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-((ls,3s)-3-hydroxycyclobutoxy)ethyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (150 mg, 72.2% yield, 90% purity) as a brown solid. LCMS (ESI, m / z): 582.3 [M+H]+.Step 8:

[0301] A solution ofN-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)- 1 -(2-(( 1 s,3s)-3 -hydroxycyclobutoxy)ethyl)- lH-pyrrolo[2,3-c]pyridine-7-carboxamide (100 mg, 0.17 mmol) and Dess-Martin periodinane (87 mg, 0.20 mmol) in DCM (2 mL) was stirred at 0 °C for 2 h under air atmosphere. The residue was purified by Prep-TLC (CH2Q2 / MeOH = 12: 1) to afford N-(3 -carbamoylphenyl)-2-(4-(2,5 -dimethyl-3 -oxo-2,3 -dihydroisoxazol-4-yl)phenyl)- 1 -(2-(3 -oxocyclobutoxy)ethyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (50 mg, 50.2% yield). LCMS (ESI, m / z): 580.2 [M+H]+.Intermediate 4Step 1:

[0302] To a stirred solution of 2-((l-(tert-butoxycarbonyl)piperidin-4-yl)oxy)acetic acid (2 g, 7.71 mmol) in THE (50 mL) was added Borane-tetrahydrofuran complex(1.0M in THF, 15.0 mL, 15.0 mmol) dropwise at 0 °C. The resulting mixture was stirred at 0 °C for 4 h. The reaction was poured into MeOH at 0 °C. The resulting mixture was concentrated under reduced pressure. The crude product was used in the next step directly without further purification.Step 2:

[0303] To a stirred solution of tert-butyl 4-(2 -hydroxyethoxy )piperidine- 1 -carboxylate (500 mg, 2.04 mmol) and TEA (825 mg, 8.15 mmol) in DCM (20 mL) was added TsCl (583 mg, 3.06 mmol) at 0 °C. The resulting mixture was stirred at room temperature for 5 h. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / WSGR Docket No. 66412-753.601EA (7: 1) to afford tert-butyl 4-(2-(tosyloxy)ethoxy)piperidine-l -carboxylate (500 mg, 61.4%) as yellow oil.Step 3:

[0304] To a stirred mixture of methyl 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (439 mg, 1.10 mmol) in DMF (5 mL) was added Cs₂CO₃ (538 mg, 1.65 mmol) at room temperature under nitrogen atmosphere. The resulting mixture was stirred at 80 °C for additional 2 h. The reaction was quenched with water at room temperature. The resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reverse phase flash (column, Cl 8 spherical; mobile phase, MeCN in Water (lOmmol / L FA), 0%to 100% gradient in 20 min; detector, UV 254 nm.) to afford methyl l-(2-((l-(tert-butoxycarbonyl)piperidin-4-yl)oxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (200 mg, 61.5%) as yellow oil. LCMS (ESI, m / z): 591 [M+H]+.Step 4:

[0305] A solution of methyl l-(2-((l-(tert-butoxycarbonyl)piperidin-4-yl)oxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (200 mg, 0.34 mmol) in THF (3 mL) and H2O (1 mL) was treated with LiOH·H2O (71 mg, 1.69 mmol) at room temperature. The resulting mixture was stirred at 50°C for 2 h. The mixture was acidified to pH 4 with HC1 (4N). The resulting mixture was purified directly by reverse phase flash (column, C18 spherical; mobile phase, MeCN in Water (lOmmol / L FA), 0% to 100% gradient in 20 min; detector, UV 254 nm.) to afford l-(2-((l-(tert-butoxycarbonyl)piperidin-4-yl)oxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxylic acid (140 mg, 71.7%) as a yellow solid. LCMS (ESI, m / z): 577 [M+H]+.Example 1. N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-(2-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-l-oxoisoindolin-5-yl)piperidin-l-yl)ethoxy)ethoxy)ethyl)-IH-pyrrolo [2,3-c] pyridine-7-carboxamideWSGR Docket No. 66412-753.601Step 1:

[0306] To a stirred solution of methyl 2-[4-(2,5-dimethyl-3-oxo-l,2-oxazol-4-yl)phenyl]-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (463 mg, 1.27 mmol, 1 equiv) and 12-bromo-2,2,3,3-tetramethyl-4,7, 10-trioxa-3 -siladodecane (500.5 mg, 1.53 mmol, 1.2 equiv) in DMSO (10 mL) was added K2CO3 (528.3 mg, 3.82 mmol, 3 equiv) in portions at room temperature under air atmosphere. Then the mixture was stirred at 100°C for 4h. The resulting mixture was filtered, the filter cake was washed with DMSO (lx 2mL). The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (0.1% TFA), 10% to 50% gradient in 10 min; detector, UV 254 nm. This resulted in methyl 2-[4-(2,5-dimethyl-3-oxo-l,2-oxazol-4-yl)phenyl]-l-(2, 2, 3, 3 -tetramethyl -4, 7, 10-trioxa-3-siladodecan-12-yl)pyrrolo[2,3-c]pyridine-7 -carboxylate (528 mg, 68.0 % yield, 90% purity) as a yellow oil. LCMS (ESI, m / z): 496.20 [M+H]+.Step 2:

[0307] To a stirred solution of methyl 2-[4-(2, 5-dimethyl-3-oxo-l,2-oxazol-4-yl)phenyl]-l-(2, 2,3,3-tetramethyl-4,7,10-trioxa-3-siladodecan-12-yl)pyrrolo[2,3-c]pyridine-7-carboxylate (70 mg, 0.12 mmol, 1 equiv) in THF (1 mL) was added LiOH (0.56 mL, 0.56 mmol, 4.9 equiv) dropwise at 0°C under air atmosphere. Then the mixture was stirred at room temperature overnight. The aqueous layer was extracted with EtOAc (3 x 1 mL). The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (0.1% FA), 10% to 50% gradient in 10 min; detector, UV 254 nm. This resulted in 2-[4-(2,5-dimethyl-3-oxo-l,2-oxazol-4-yl)phenyl]-l-(2,2,3,3-tetramethyl-4,7,10-trioxa-3-siladodecan-12-yl)pyrrolo[2,3-c]pyridine-7-carboxylic acid (25 mg, 36.6% yield, 99% purity) as a light yellow solid. LCMS (ESI, m / z): 482.15 [M+H]+.WSGR Docket No. 66412-753.601Step 3:

[0308] To a stirred solution of 2-[4-(2,5-dimethyl-3-oxo-l,2-oxazol-4-yl)phenyl]-l-{2-[2-(2-hydroxyethoxy)ethoxy]ethyl}pyrrolo[2,3-c]pyridine-7-carboxylic acid (25 mg, 0.05 mmol, 1 equiv) and 3 -aminobenzamide (8.5 mg, 0.06 mmol, 1.2 equiv) in DMF (1 mL) was added DIEA (13.4 mg, 0.10 mmol, 2 equiv) dropwise at 0°C under air atmosphere. Then the mixture was stirred at 0°C for 15min. To the above mixture was added HATU (23.7 mg, 0.06 mmol, 1.2 equiv) in portions at 0°C. The resulting mixture was stirred at room temperature for additional Ih. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, MeCN in Water (0.1% TFA), 10% to 50% gradient in 10 min; detector, UV 254 nm. This resulted in N-(3-carbamoylphenyl)-2-[4-(2,5-dimethyl-3-oxo-l,2-oxazol-4-yl)phenyl]-l-{2-[2-(2-hydroxyethoxy)ethoxy]ethyl}pyrrolo[2,3-c]pyridine-7-carboxamide (28 mg, 89.3% yield, 90% purity) as a light yellow solid. LCMS (ESI, m / z): 600.25 [M+H]+.Step 4:

[0309] To a stirred solution of N-(3-carbamoylphenyl)-2-[4-(2,5-dimethyl-3-oxo-l,2-oxazol-4-yl)phenyl]-l-{2-[2-(2-hydroxyethoxy)ethoxy]ethyl}pyrrolo[2,3-c]pyridine-7-carboxamide (25 mg, 0.04 mmol, 1 equiv) and TsCl (8.4 mg, 0.04 mmol, 1.05 equiv) in DCM (1 mL) were added Ag2O (14.5 mg, 0.06 mmol, 1.5 equiv) and Nal (6.9 mg, 0.05 mmol, 1.1 equiv) in portions at 0°C under air atmosphere. Then the mixture was stirred at room temperature for overnight. The resulting mixture was fdtered, the filter cake was washed with DCM (lx 1mL). The filtrate was concentrated under reduced pressure. The residue was purified by Prep-TLC (CH₂Cl₂ / MeOH 20:1) to afford 2-[2-(2-{7-[(3-carbamoylphenyl)carbamoyl] -2-[4-(2,5 -dimethyl-3 -oxo- 1,2-oxazol-4-yl)phenyl]pyrrolo [2,3 -c]pyridin- 1 -yl}ethoxy)ethoxy] ethyl 4-methylbenzenesulfonate (20 mg, 63.6% yield, 95% purity) as a white solid. LCMS (ESI, m / z): 754.40 [M+H]+.Step 5:

[0310] To a stirred solution of 2-[2-(2-{7-[(3-carbamoylphenyl)carbamoyl]-2-[4-(2,5-dimethyl-3-oxo-1,2-oxazol-4-yl)phenyl]pyrrolo[2,3 -c]pyridin- 1 -yl} ethoxy)ethoxy] ethyl 4-methylbenzenesulfonate (30 mg, 0.04 mmol, 1 equiv) and 3-[l-oxo-5-(piperidin-4-yl)-3H-isoindol-2-yl]piperidine-2, 6-dione (19.5 mg, 0.06 mmol, 1.5 equiv) in MeCN (0.5 mL) were added K2CO3 (16.5 mg, 0.12 mmol, 3 equiv) in portions at room temperature under air atmosphere. Then the mixture was stirred at 80°C for Ih. The mixture was allowed to cool down to room temperature. The resulting mixture was filtered, the filter cake was washed with MeCN (lx ImL). The filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: X-Select Prep OBD C18 Column, 30*150 mm, 5pm; Mobile Phase A: Water(0.1%FA), Mobile Phase B: ACN; Flow rate: 60 mL / min mL / min; Gradient (B%): 18% B to30% B in 10 min; Wave Length: 254nm / 220nm nm;RTl(min): 7.93) to afford N-(3-carbamoylphenyl)-2-[4-(2,5-dimethyl-3-oxo-l,2-oxazol-4-yl)phenyl]-l-{2-[2-(2-{4-[2-(2,6-dioxopiperidin-3-yl)-l-oxo-3H-isoindol-5-yl]piperidin-l-yl}ethoxy)ethoxy]ethyl}pyrrolo[2,3-c]pyridine-7-carboxamide (2.3 mg, 6.4% yield). LCMS (ESI, m / z): 909.45 [M+H]+. 'H NMR (400 MHz, CDCh) 5 10.40 (s, IH), 8.34 (s, IH), 8.30 (d, J= 5.1 Hz, IH), 8.17WSGR Docket No. 66412-753.601(s, 1H), 8.06 (d, J= 8.1 Hz, 1H), 7.81 (d, J= 7.9Hz, 1H), 7.73 (d, J= 8.3 Hz, 3H), 7.64 (d, J= 8.2 Hz, 3H), 7.50 (t, J= 7.8 Hz, 1H), 7.37 (s, IH), 7.30 (d, J= 2.5 Hz, 1H), 6.70 (s, 2H), 5.90 (s, 1H), 5.22 (dd, J = 13.3, 5.2 Hz, 1H), 5.09 (s, 2H), 4.46 (d, J= 16.1 Hz, 1H), 4.34 (d, J= 16.1 Hz, 1H), 3.65 (m, 5H), 3.44 (m, 4H), 3.31 (s, 2H), 3.22 (s, 2H), 1.86 (m, 8H), 2.79 (d, J= 92.5 Hz, 5H), 2.49 (s, 3H), 1.28 (s, 1H), 0.89 (s, 1H).Example 2. N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-(2-(2-(4-(2-(2,6-dioxopiperidin-3-yl)-l,3-dioxoisoindolin-5-yl)piperazin-l-yl)ethoxy)ethoxy)ethyl)- IH-pyrr olo [2,3-c] pyridine-7-carboxamide

[0311] To a stirred solution of 2-[2-(2-{7-[(3-carbamoylphenyl)carbamoyl]-2-[4-(2,5-dimethyl-3-oxo-1,2-oxazol-4-yl)phenyl]pyrrolo[2,3 -c]pyridin- 1 -yl} ethoxy)ethoxy] ethyl 4 -methylbenzene sulfonate (25 mg, 0.03 mmol, 1 equiv) and 2-(2,6-dioxopiperidin-3-yl)-5-(piperazin-l-yl)isoindole-l, 3-dione (17.0 mg, 0.05 mmol, 1.5 equiv) in MeCN (1 mL) was added K2CO3 (13.8 mg, 0.10 mmol, 3 equiv) in portions at room temperature under air atmosphere. Then the mixture was stirred at 80°C for Ih. The mixture was allowed to cool down to room temperature. The resulting mixture was filtered, the filter cake was washed with MeCN (lx ImL). The filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: X-Select Prep OBD Cl 8 Column, 30* 150 mm, 5pm; Mobile Phase A: Water(0.1%FA), Mobile Phase B: ACN; Flow rate: 60 mL / min mL / min; Gradient (B%): 18% B to30% B in 10 min; Wave Length: 254nm / 220nm nm; RTl(min): 7.58) to afford N-(3-carbamoylphenyl)-2-[4-(2,5-dimethyl-3-oxo-l,2-oxazol-4-yl)phenyl]-l-{2-[2-(2-{4-[2-(2,6-dioxopiperidin-3-yl)-l,3-dioxoisoindol-5-yl]piperazin-l-yl}ethoxy)ethoxy]ethyl}pyrrolo[2,3-c]pyridine-7-carboxamide (2.3 mg, 7.5% yield). LCMS (ESI, m / z): 924.20[M+H]+. 'HNMR (400 MHz, CDCh) 5 10.47 (s, IH), 8.35 (s, IH), 8.30 (d, J= 5.0 Hz, IH), 8.23 (s, IH), 7.98 (d, J= 8.0 Hz, IH), 7.84 - 7.42 (m, 9H), 7.21 (s, 2H), 7.03 (d, J= 6.2 Hz, IH), 6.73 (s, IH), 5.91 (s, IH), 5.24 - 4.86 (m, 3H), 3.71 (s, 8H), 3.64 - 2.99 (m, 1 IH), 2.98 - 2.70 (m, 4H), 2.49 (s, 3H), 2.36 (s, 2H), 2.17 (s, IH).WSGR Docket No. 66412-753.601Example 30 and 31Example 31 Step 1:

[0312] A solution of tert-butyl 4-(3-(2,6-dioxopiperidin-3-yl)-l-methyl-lH-indazol-6-yl)piperidine-l-carboxylate (1 g, 2.345 mmol) in DCM (10 mL) was treated with HCl in 1,4-dioxane (4.0 M) (10 m ) at room temperature for 1 h. The resulting mixture was concentrated under reduced pressure. This resulted in 3-(l-methyl-6-(piperidin-4-yl)-lH-indazol-3-yl)piperidine-2, 6-dione (0.75 g) as a white solid. The crude product was used in the next step directly without further purification. LCMS (ESI, m / z): 327.2 [M+H]+.Step 2

[0313] A solution ofN-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-(3-oxocyclobutoxy)ethyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (55 mg, 0.095 mmol), 3-(l-methyl-6-(piperidin-4-yl)-lH-indazol-3-yl)piperidine-2, 6-dione (62 mg, 0.19 mmol) in DCM (2 mL), MeOH (2 mL) was treated with AcONa (16 mg, 0.19 mmol) at room temperature for 15 min under air atmosphere followed by the addition of HOAc (11 mg, 0.19 mmol) dropwise at room temperature. After the resulting mixture was stirred 30 min. To the above mixture was added NaBHsCN (30 mg, 0.475 mmol). The resulting mixture was stirred at room temperature for additional 1 h. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (0.1% TFA), 30% to 50% gradient in 20 min; detector, UV 254 nm. This resulted in N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-WSGR Docket No. 66412-753.601yl)phenyl)- 1 -(2-(3 -(4-(3 -(2,6-dioxopiperidin-3 -yl)- 1 -methyl- lH-indazol-6-yl)piperidin- 1 -yl)cyclobutoxy)ethyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (30 mg) as a white solid.Step 3:

[0314] The crude product was purified by Prep-Achiral-SFC with the following conditions (Column: DAICEL DCpak PMPC 3*25 cm, 5um; Mobile Phase A: CO2, Mobile Phase B: MeOH(0.3%-7M-NH3-MeOH); Flow rate: 80 mL / min; Gradient (B%): isocratic 40% B; Column Temperature (°C): 35; Back Pressure(bar): 100; Wave Length: 220 nm; RTl(min): 5.65; RT2(min): 6.65; Pressure(Bar): 100; Sample Solvent: MeOH; Injection Volume: 1 mL; Number Of Runs: 3) to afford Example 30 (2.9 mg, 3% yield, 99.4% purity) and Example 31 (9.5 mg, 11% yield, 98.7% purity).

[0315] Example 30: N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)- 1 -(2-(( lr,3r)-3-(4-(3-(2,6-dioxopiperidin-3-yl)- 1 -methyl- lH-indazol-6-yl)piperidin- 1 -yl)cyclobutoxy)ethyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide. LCMS (ESI, m / z): 890.4 [M+H]+. ’H NMR (400 MHz, DMSO-d6) 5 10.92 (s, 1H), 10.88 (s, 1H), 8.40 - 8.39 (m, 1H), 8.32 (d, J = 5.2 Hz, 1H), 8.25 (s, 2H), 8.03 - 7.97 (m, 2H), 7.86 - 7.78 (m, 3H), 7.71 - 7.69 (m, 2H), 7.64 (d, J = 7.8 Hz, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.47 (t, J = 7.9 Hz, 1H), 7.40 (d, J = 7.0 Hz, 2H), 7.00 (d, J = 8.4 Hz, 1H), 6.83 (s, 1H), 4.72 - 4.69 (m, 2H), 4.33-4.30 (m, 1H), 3.96 (s, 3H), 3.54 - 3.51 (m, 3H), 3.48 (s, 3H), 3.26 (d, J = 11.1 Hz, 2H), 2.72 -2.58 (m, 4H), 2.43 - 2.31 (m, 2H), 2.16 (dd, J = 13.4, 5.6 Hz, 1H), 1.69 (d, J = 13.9 Hz, 5H), 1.65 - 1.50 (m, 4H), 1.55 - 1.49 (m, 2H), 1.24(s, 1H).

[0316] Example 31: N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)- 1 -(2-(( 1 s,3 s) -3 -(4-(3 -(2,6-dioxopiperidin-3 -yl)- 1 -methyl- lH-indazol-6-yl)piperidin- 1 -yl)cyclobutoxy)ethyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide. LCMS (ESI, m / z): 890.4 [M+H]+. ’H NMR (400 MHz, DMSO-d6) 5 10.94 (s, 1H), 10.88 (s, 1H), 8.40 (t, J = 1.9 Hz, 1H), 8.31 (d, J = 5.2 Hz, 1H), 8.27 (s, 1H), 8.03 - 7.94 (m, 2H), 7.85 - 7.78 (m, 3H), 7.71-7.69 (m, 2H), 7.65-7.58 (m, 2H), 7.47 (t, J = 7.9 Hz, 1H), 7.41 - 7.38 (m, 2H), 7.01 (dd, J = 8.5, 1.2 Hz, 1H), 6.82 (s, 1H), 4.65 (t, J = 6.1 Hz, 2H), 4.33 (dd, J = 9.7, 5.1 Hz, 1H), 3.97 (s, 3H), 3.48 (s, 3H), 3.30 - 3.25 (m, 3H), 2.70 - 2.54 (m, 4H), 2.50 - 2.48(m, 4H), 2.40 - 2.30 (m, 1H), 2.21 - 2.12 (m, 1H), 2.05 - 1.97 (m, 3H), 1.78 - 1.58 (m, 6H), 1.26 - 1.18 (m, 2H).WSGR Docket No. 66412-753.601Example 19 and 20Step 1:

[0317] To a stirred solution of l-(2-((l-(tert-butoxycarbonyl)piperidin-4-yl)oxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxylic acid (140 mg, 0.24 mmol) and 3 -aminobenzamide (43 mg, 0.31 mmol) in DMF (5 mL) was added DIEA (125 mg, 0.97 mmol) dropwise at 0 °C under air atmosphere. Then the mixture was stirred at 0 °C for 15 min. To the above mixture was added HATU (138 mg, 0.36 mmol) in portions at 0 °C. The resulting mixture was stirred at room temperature for additional 1 h. The mixture was purified directly by reversed-phase flash chromatography (column, C18 spherical; mobile phase, MeCN in Water (lOmmol / L FA), 0% to 100% gradient in 20 min; detector, UV 254 nm.) to afford tert-butyl 4-(2-(7-((3-carbamoylphenyl)carbamoyl)-2-(4-(2,5 -dimethyl-3 -oxo-2,3 -dihydroisoxazol-4-yl)phenyl)- IH-pyrrolo [2,3 -c]pyridin- 1 -yl)ethoxy)piperidine-l -carboxylate (150 mg, 88.9%) as a yellow solid. LCMS (ESI, m / z): 695 [M+H]+.Step 2:

[0318] A solution of tert-butyl 4-(2-(7-((3-carbamoylphenyl)carbamoyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)- lH-pyrrolo[2,3-c]pyridin- 1 -yl)ethoxy)piperidine- 1 -carboxylate (150 mg, 0.21 mmol) in HC1 (4.0 M in 1,4-dioxane, 2 mL) was stirred at room temperature for 1 h. The resulting mixture was concentrated under reduced pressure. The crude product was used in the next step directly without further purification. LCMS (ESI, m / z): 595 [M+H]+.WSGR Docket No. 66412-753.601Step 3:

[0319] To a stirred solution of N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-(piperidin-4-yloxy)ethyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (55 mg, 0.092 mmol) and l-(4-(2,6-dioxopiperidin-3-yl)-3,5-difluorophenyl)azetidine-3-carboxylic acid (30 mg, 0.092 mmol) in DMF (2 mb) was added HATU (53 mg, 0.138 mmol) in portions at room temperature. The resulting mixture was stirred at room temperature for 5 min. To the above mixture was added DIEA (60 mg, 0.46 mmol) dropwise at 0 °C. The resulting mixture was stirred at room temperature for additional Ih. The reaction was monitored by LCMS. The mixture was purified directly by reverse phase flash (column, Cl 8 spherical; mobile phase, MeCN in Water (lOmmol / L FA), 0% to 100% gradient in 20 min; detector, UV 254 nm.) to afford N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-((l-(l-(4-(2,6-dioxopiperidin-3-yl)-3,5-difluorophenyl)azetidine-3-carbonyl)piperidin-4-yl)oxy)ethyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (43.0 mg, 51.6%) as a white solid.

[0320] LCMS (ESI, m / z): 901 [M+H]+. 'H NMR (400 MHz, DMSO-d6) 5 10.95 (s, IH), 10.86 (s, IH), 8.40 (s, IH), 8.31 (d, J = 5.2 Hz, IH), 8.03 - 7.97 (m, 2H), 7.83 - 7.79 (m, 3H), 7.73 - 7.67 (m, 2H), 7.63 (d, J = 8.8 Hz, IH), 7.46 (t, J = 8.0 Hz, IH), 7.40 (s, IH), 6.83 (s, IH), 6.14 (d, J = 11.2 Hz, 2H), 4.74 -4.66 (m, IH), 4.06 - 4.01 (m, IH), 3.95 (t, J = 8.0 Hz, 2H), 3.81 (t, J = 6.8 Hz, 2H), 3.70 - 3.62 (m, IH), 3.49 (s, 3H), 3.41 (t, J = 5.6 Hz, 2H), 3.31 - 3.29 (m, IH), 3.27 - 3.19 (m, IH), 3.13 - 3.04 (m, IH), 3.02 - 2.89 (m, 2H), 2.83 - 2.73 (m, 2H), 2.50 (s, 3H), 2.14 - 2.01 (m, IH), 1.99 - 1.85 (m, IH), 1.47 - 1.22 (m, 2H), 1.08 - 0.90 (m, 2H).Step 4:

[0321] N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-((l-(l-(4-(2,6-dioxopiperidin-3-yl)-3,5-difluorophenyl)azetidine-3-carbonyl)piperidin-4-yl)oxy)ethyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (37 mg) was separated by Prep-Chiral HPLC (Column:CHIRALPAK IF, 20*250mm, 5 pm; Mobile Phase A: EtOH: DCM=1: 1-HPLC, Mobile Phase B: Hex (0.1% FA)-HPLC; Flow rate: 20 mL / min; Gradient (B%): 20% B to 20% B in 18min; Wave Length: 220 / 254 nm; RTl(min): 8.26; RT2(min): 14.67) to obtain (S)-N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-((l-(l-(4-(2,6-dioxopiperidin-3-yl)-3,5-difluorophenyl)azetidine-3-carbonyl)piperidin-4-yl)oxy)ethyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (Example 19, the first eluting peak, 12.8 mg, 34.5%) and (R)-N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-((l-(l-(4-(2,6-dioxopiperidin-3-yl)-3,5-difluorophenyl)azetidine-3-carbonyl)piperidin-4-yl)oxy)ethyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (Example 20, the second eluting peak, 12.9 mg, 34.8%).

[0322] Example 19: LCMS (ESI, m / z): 901.3 [M+H]+. 'H NMR (400 MHz, DMSO-d6) 5 10.95 (s, IH), 10.86 (s, IH), 8.40 (t, J = 2.0 Hz, IH), 8.31 (d, J = 5.2 Hz, IH), 8.00 - 7.95 (m, 2H), 7.86 - 7.77 (m, 3H), 7.71 - 7.68 (m, 2H), 7.63 (d, J = 7.2 Hz, IH), 7.46 (t, J = 8.0 Hz, IH), 7.40 (s, IH), 6.83 (s, IH), 6.14 (d, J = 11.2 Hz, 2H), 4.75 - 4.70 (m, IH), 4.06 - 4.00 (m, IH), 3.95 (t, J = 8.0 Hz, 2H), 3.81 (t, J = 6.8 Hz, 2H), 3.70 - 3.62 (m, IH), 3.49 (s, 3H), 3.41 (t, J = 5.6 Hz, 2H), 3.26 - 3.18 (m, IH), 3.11 - 3.05 (m, IH),WSGR Docket No. 66412-753.6013.01 - 2.89 (m, 2H), 2.84 - -2.72 (m, 2H), 2.50 (s, 3H), 2.14 - 2.00 (m, 1H), 1.98 - 1.90 (m, 1H), 1.43 -1.25 (m, 2H), 1.11 - 0.87 (m, 2H).

[0323] Example 20: LCMS (ESI, m / z): 901.6 [M+H]+. ’HNMR (400 MHz, DMSO-d6) 5 10.95 (s, 1H), 10.86 (s, 1H), 8.40 (t, J = 2.0 Hz, 1H), 8.31 (d, J = 5.2 Hz, 1H), 7.99 - 7.96 (m, 2H), 7.83 - 7.77 (m, 3H), 7.72 - 7.68 (m, 2H), 7.63 (d, J = 7.2 Hz, 1H), 7.46 (t, J = 8.0 Hz, 1H), 7.40 (s, 1H), 6.83 (s, 1H), 6.14 (d, J = 11.2 Hz, 2H), 4.76 - 4.62 (m, 1H), 4.07 - 3.99 (m, 1H), 3.95 (t, J = 8.0 Hz, 2H), 3.81 (t, J = 6.8 Hz, 2H), 3.72 - 3.60 (m, 1H), 3.49 (s, 3H), 3.41 (t, J = 5.6 Hz, 2H), 3.27 - 3.19 (m, 1H), 3.13 - 3.04 (m, 1H), 3.01 - 2.88 (m, 2H), 2.84 - 2.71 (m, 2H), 2.50 (s, 3H), 2.15 - 2.01 (m, 1H), 1.99 - 1.89 (m, 1H), 1.45 -1.21 (m, 3H), 1.09 - 0.89 (m, 2H).Example 52Step 1:

[0324] To a stirred solution / mixture of methyl 5-chloro-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-ethyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (600 mg, 1.41 mmol) and NlLBoc (330 mg, 2.82 mmol) in Dioxane (12 mL) was added XPhos (134 mg, 0.28 mmol), Cs₂CO₃ (11.4 g, 4.22 mmol) and Pd₂(dba)₃ (129 mg, 0.14 mmol) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred at 100 °C for 2 h under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. The resulting mixture was fdtered, the filter cake was washed with ethyl acetate (3 x 10 mL). The filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (10 mmol / L NH4HCO3), 0% to 100% gradient in 20 min; detector, UV 254 nm. This resulted in methyl 5-((tert-butoxycarbonyl)amino)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-WSGR Docket No. 66412-753.601yl)phenyl)-l-ethyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (480 mg, 67.3% yield, 90% purity). LCMS (ESI, m / z): 507.3 [M+H]+.Step 2:

[0325] To a stirred mixture of methyl 5-((tert-butoxycarbonyl)amino)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-ethyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (300 mg, 0.592 mmol) in DCM (3 mL) was added HCl in dioxane (3 mL) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 2 h under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (10 mmol / L NH4HCO3), 0% to 100% gradient in 20 min; detector, UV 254 nm. This resulted in methyl 5-amino-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-ethyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (180 mg, 74.8% yield, 90% purity) as an off-white solid. LCMS (ESI, m / z): 407.1 [M+H]+.Step 3:

[0326] To a stirred solution of methyl 5-amino-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-ethyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (400 mg, 0.98 mmol) in H2O (13.2 mL) was added H2SO4 (0.8 mL) dropwise at 0 °C under nitrogen atmosphere. NaNO2 (163 mg, 2.36 mmol) in H2O (1.2 mL) was added dropwise at 0 °C. The resulting mixture was stirred at room temperature for additional 1 h. The reaction was quenched with sat. NaHCO3 (aq.) 30 mL at 0 °C. The aqueous layer was extracted with CH2Cl2 (3 x 10 mL). The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, MeCN in Water (10 mmol / L NH4HCO3), 10% to 50% gradient in 10 min; detector, UV 254 nm. This afforded methyl 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-ethyl-5-hydroxy-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (100 mg) as a light yellow solid. LCMS (ESI, m / z): 408.10 [M+H]+.Step 4:

[0327] A solution of methyl 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-ethyl-5-hydroxy-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (200 mg, 0.49 mmol) in DMF (6 mL) was treated with allyl bromide (119 mg, 0.98 mmol) at room temperature for 10 min under nitrogen atmosphere followed by the addition of K2CO3 (204 mg, 1.47 mmol) dropwise at room temperature. The resulting mixture was stirred at 70 °C for 2 h under nitrogen atmosphere. The resulting mixture was concentrated under vacuum. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (0.1% FA), 10% to 50% gradient in 10 min; detector, UV 254 nm. This resulted in methyl 5-(allyloxy)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-ethyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (110 mg, 50.1% yield, 95% purity) as a yellow solid. LCMS (ESI, m / z): 449.2 [M+H]+.WSGR Docket No. 66412-753.601Step 5:

[0328] A solution of methyl 5-(allyloxy)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-ethyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (100 mg, 0.22 mmol) in THF (2 mL), H2O (0.5 mL) was treated with LiOH.H2O (2.00 mL, 4.0 mmol) at room temperature for 10 min under nitrogen atmosphere. The resulting mixture was stirred at 50 °C for 2 h under nitrogen atmosphere. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (0.1% FA), 10% to 50% gradient in 10 min; detector, UV 254 nm. This resulted in 5-(allyloxy)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-ethyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylic acid (60 mg) as a white solid. LCMS (ESI, m / z): 434.2 [M+H]+.Step 6:

[0329] A solution of 5-(allyloxy)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-ethyl-lH-pyrrolo[2,3-c]pyridine-7 -carboxylic acid (70 mg, 0.16 mmol) in DMF (1 mL) was treated with HATU (92 mg, 0.24 mmol), DIEA (63 mg, 0.48 mmol) at room temperature for 2 h under nitrogen atmosphere followed by the addition of 3 -aminobenzamide (28.6 mg, 0.20 mmol) dropwise at room temperature. The resulting mixture was stirred at room temperature for 1 h under nitrogen atmosphere. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (0.1% FA), 10% to 50% gradient in 10 min; detector, UV 254 nm. This resulted in 5-(allyloxy)-N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-ethyl-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (50 mg, 56.1% yield, 95% purity) as a white solid. LCMS (ESI, m / z): 552.3 [M+H]+.Step 7:

[0330] A solution of 5-(allyloxy)-N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-ethyl-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (50 mg, 0.09 mmol,) in THF (1 mL), H2O (0.5 mL) was treated with N-Methylmorpholine N-oxide (22 mg, 0.18 mmol), Potassium osmate(VI) dihydrate (7 mg, 0.02 mmol) at 0°C for 5 min under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 2 h under nitrogen atmosphere. The residue was purified by silica gel column chromatography, eluted with PE / EA (1: 1) to afford N-(3-carbamoylphenyl)-5-(2,3-dihydroxypropoxy)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-ethyl-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (35 mg, 65.9% yield, 95% purity) as a white solid. LCMS (ESI, m / z): 586.3 [M+H]+.Step 8:

[0331] A solution of N-(3 -carbamoylphenyl) -5 -(2,3 -dihydroxypropoxy)-2-(4-(2,5 -dimethyl-3 -oxo-2,3 -dihydroisoxazol-4-yl)phenyl)-l-ethyl-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (30 mg, 0.05 mol) in MeOH (2 mL) was treated with NalCL (33 mg, 0.15 mmol) at 0 °C for 10 in under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 24 h under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The resulting mixture was diluted with DMF (3 mL). The residue was purified by reversed-phase flash chromatography with the following conditions: column,WSGR Docket No. 66412-753.601C 18 silica gel; mobile phase, MeCN in Water (10 mmol / L NH4HCO3), 10% to 50% gradient in 10 min; detector, UV 254 nm. This resulted in N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-ethyl-5-(2-oxoethoxy)-lH-pyrrolo[2,3-c]pyridine-7 -carboxamide (25 mg, 88.2% yield, 95% purity) as a white solid. LCMS (ESI, m / z): 554.2 [M+H]+.Step 9:

[0332] A solution of N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-ethyl-5-(2-oxoethoxy)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (30 mg, 0.05 mmol) in MeOH (1 mL) was treated with 3-(l-oxo-5-(l-(piperidin-4-ylmethyl)piperidin-4-yl)isoindolin-2-yl)piperidine-2, 6-dione (46 mg, 0.11 mmol), AcONa (14 mg, 0.16 mmol) at room temperature for 10 min under nitrogen atmosphere followed by the addition of HOAc (17 mg, 0.27 mmol) dropwise at room temperature. To the above mixture was added NaBH3CN (10 mg, 0.16 mmol) in portions over 2 h at room temperature. The resulting mixture was stirred at room temperature for additional 2 h. The resulting mixture was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: XBridge Prep OBD C18 Columnl9*250 mm, 5pm; Mobile Phase A: Water(10 mmol / L NH4HCO3+0.1%NH3.H2O). Mobile Phase B: ACN; Flow rate: 20 mL / min; Gradient (B%): 65% B to 85% B in 7 min; Wave Length: 254 nm / 220 nm; RTl(min): 8.41) to afford N-(3-carbamoylphenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-5-(2-(4-((4-(2-(2,6-dioxopiperidin-3 -yl)- 1 -oxoisoindolin-5 -yl)piperidin- 1 -yl)methyl)piperidin- 1 -yl)ethoxy) - 1 -ethyl- 1 H-pyrrolo[2,3-c]pyridine-7-carboxamide (18.7 mg, 35.9% yield, 95.2% purity). LCMS (ESI, m / z): 962.6 [M+H]+. 'H NMR (400 MHz, DMSO-d6) 5 10.99 (s, 1H), 10.80 (s, 1H), 8.31 (t, J=2.0Hz, 1H), 8.14 (s, 1H), 8.01 - 7.96 (m, 2H), 7.85 - 7.76 (m, 2H), 7.71 - 7.63 (m, 4H), 7.51 - 7.45 (m, 2H), 7.40 (d, J= 7.2 Hz, 2H), 7.18 (s, 1H), 6.67 (s, 1H), 5.11 (dd, J= 13.2, 5.2 Hz, 1H), 4.61 - 4.58 (s, 2H), 4.45 - 4.28 (m, 4H), 3.50 (s, 3H), 3.41 - 3.39 (m, 3H), 3.10 - 3.03 (m, 5H), 2.94 - 2.88 (m, 1H), 2.78 - 2.58 (m, 3H), 2.39 - 2.36 (m, 4H), 2.33 - 2.31 (m, 3H), 2.21 - 2.19 (m, 2H), 1.83 - 1.79 (m, 8H), 1.29 - 1.21 (m, 3H), 0.96 (t, J= 7.2 Hz, 3H).WSGR Docket No. 66412-753.601Example 56Step 1:

[0333] To a stirred solution of 3-(2,6-bis(benzyloxy)pyridin-3-yl)-6-bromo-l-methyl-lH-indazole (5.0 g, 10.0 mmol) and l,4-dioxa-8-azaspiro[4.5]decane (1.72 g, 12.0 mmol) in dioxane (100 mL) was added RuPhos Pd G3 (0.84 g, 1.0 mmol) and t-BuONa (2.88 g, 30.0 mmol) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred at 100 °C for 1 h under nitrogen atmosphere. The resulting mixture was diluted with water (200 mL) and extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine (2 x 100 mL), dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel with petrol ether / EtOAc (4 / 1) to afford 8 -(3 -(2,6-bis(benzyloxy)pyridin-3 -yl)- 1 -methyl- lH-indazol-6-yl)- 1,4-dioxa-8-azaspiro [4.5] decane (3 g, 53.4%yield, 96%purity) as a yellow oil. LCMS (ESI, m / z): 563.2 [M+H]+.Step 2:

[0334] To a solution of 8-(3-(2,6-bis(benzyloxy)pyridin-3-yl)-l-methyl-lH-indazol-6-yl)-l,4-dioxa-8-azaspiro[4.5]decane (3 g, 5.33 mmol) in ethyl acetate (30 mL) and DMF (3 mL) was added Pd / C (10% w / w, 2.40 g, 22.55 mmol) under nitrogen atmosphere in a 20 mL round-bottom flask. The mixture was hydrogenated at 50 °C overnight under hydrogen atmosphere using a hydrogen balloon. The reaction was filtered through a Celite pad and the filtrate was concentrated under reduced pressure. This resulted in 3-(l-methyl-6-(l,4-dioxa-8-azaspiro[4.5]decan-8-yl)-lH-indazol-3-yl)piperidine-2, 6-dione (1.5 g, 73.2%yield) as a yellow solid. LCMS (ESI, m / z): 385.2 [M+H]+.Step 3:

[0335] A solution of 3-(l-methyl-6-(l,4-dioxa-8-azaspiro[4.5]decan-8-yl)-lH-indazol-3-yl)piperidine-2, 6-dione (2 g, 5.20 mmol) and formic acid (239 mg, 5.20 mmol) in H2O (20 mL) was stirred at 70 °C overnight under air atmosphere. The resulting mixture was concentrated under reduced pressure. ThisWSGR Docket No. 66412-753.601resulted in 3-(l-methyl-6-(4-oxopiperidin-l-yl)-lH-indazol-3-yl)piperidine-2, 6-dione (1.5 g, 84.7%yield) as a brown solid. LCMS (ESI, m / z): 340.1 [M+H]+.Step 4:

[0336] To a stirred solution of 3-(l-methyl-6-(4-oxopiperidin-l-yl)-lH-indazol-3-yl)piperidine-2,6-dione (15 mg, 0.044 mmol) and l-(2-(azetidin-3-yloxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-5-methyl-N-(6-methylpyridazin-3-yl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (24 mg, 0.04 mmol) in DCM (1 m ) were added HOAc (5 mg, 0.09 mmol) and MeOH (1 m ) in portions at room temperature under air atmosphere. The resulting mixture was stirred at room temperature for 1 h under air atmosphere. To the above mixture was added NaBHsCN (4 mg, 0.06 mmol) in portions over 1 min at 0°C. The resulting mixture was stirred at room temperature for additional 1 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by Prep-HPLC (Column: Waters Xselect C18 OBD Column 30*150mm 5 µm; Mobile Phase A: Water(0.1% FA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient (B%): 15% B to 40% B in 7.5min; Wave Length: 254 / 220 nm; RTl(min): 6.58) to afford 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)- 1 -(2-(( 1 -( 1 -(3 -(2,6-dioxopiperidin-3 -yl)- 1 -methyl- lH-indazol-6-yl)piperidin-4-yl)azetidin-3 -yl)oxy)ethyl)-5-methyl-N-(6-methylpyridazin-3-yl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (10.9 mg, 28.2% yield, 99.3%purity). LCMS (ESI, m / z): 878.6 [M+H]+. ’HNMR(400 MHz, DMSO-d6) 5 11.28 (s, 1H), 10.85 (s, 1H), 8.46 (d, J = 9.2 Hz, 1H), 7.84 - 7.77 (m, 2H), 7.73 - 7.65 (m, 4H), 7.48 (d, J = 9.2 Hz, 1H), 6.87 (dd, J = 9.2, 2.0 Hz, 1H), 6.80 (d, J = 2.0 Hz, 1H), 6.76 (s, 1H), 4.74 (t, J = 5.4 Hz, 2H), 4.25 (dd, J = 9.2, 5.2 Hz, 1H), 3.89 (s, 3H), 3.65 - 3.58 (m, 1H), 3.49 (s, 3H), 3.33 (s, 3H), 3.25 (t, J = 5.6 Hz, 2H), 3.14 (t, J = 6.4 Hz, 2H), 2.80 - 2.57 (m, 10H), 2.51 - 2.49 (m, 2H), 2.37 - 2.09 (m, 4H), 1.73 -1.70 (m, 1H), 1.54 - 1.49 (m, 2H), 1.16 - 1.05 (m, 2H).Example 110NSCI, DIEA, DCM Na2CO3, ACN, 80°C Step 3 Step 4Step 1:

[0337] To a solution of l-(2-((ls,3s)-3-(benzyloxy)cyclobutoxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylic acid (800 mg, 1.41 mmol) and DIEA (1.09 g, 8.45 mmol) in DMF (8 mb) were added HATU (804 mg, 2.1 mmol) and 5-WSGR Docket No. 66412-753.601amino-2-fluoro-N-methylbenzamide (356 mg, 2.10 mmol) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 2 h at room temperature. The reaction mixture was directly purified by flash column chromatography on Cl 8 silica with MeCN in water (0.1% FA) to afford l-(2-((ls,3s)-3-(benzyloxy)cyclobutoxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl) -N -(4-fluoro -3 -(methylcarbamoyl)phenyl) -5 -methyl- 1 H-pyrrolo [2,3 -c] pyridine -7 -carboxamide (744 mg, 97%) as a yellow solid. LCMS (ESI, m / z): 718.4 [M+H]+.Step 2:

[0338] To a solution of l-(2-((ls,3s)-3-(benzyloxy)cyclobutoxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-N-(4-fluoro-3-(methylcarbamoyl)phenyl)-5-methyl-lH-pyrrolo[2,3-c] pyridine -7-carboxamide (500 mg, 0.70 mmol) in HOAc (5 m ) was added Pd / C (10% w / w, 500 mg) at room temperature under nitrogen atmosphere. The flask was evacuated and flushed three times with nitrogen, followed by flushing with hydrogen. The mixture was stirred for 4 h at room temperature. The mixture was filtered, and the filter cake was washed with MeOH. The filtrate was concentrated under vacuum. The residue was purified by flash column chromatography on C18 silica with MeCN in water (0.1% FA) to afford 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-N-(4-fluoro-3-(methylcarbamoyl)phenyl)-l-(2-((ls,3s)-3-hydroxycyclobutoxy)ethyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (440 mg, 93%) as a yellow solid. LCMS (ESI, m / z): 628.3 [M+H]+.Step 3:

[0339] To a solution of 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-N-(4-fluoro-3-(methylcarbamoyl)phenyl)- 1 -(2-(( 1 s,3 s)-3 -hydroxy cyclobutoxy)ethyl)-5 -methyl- IH-pyrrolo [2,3 -c]pyridine-7-carboxamide (440 mg, 0.71 mmol) and DMAP (18 mg, 0.14 mmol) in DCM (7 mb) was added DIEA (453 mg, 3.51 mmol) at room temperature. To the above mixture was added 4-nitrobenzene-1 -sulfonyl chloride (311 mg, 1.40 mmol) at room temperature. The resulting mixture was stirred for 2 h at room temperature. The resulting mixture was concentrated under reduced pressure. The residue was purified by Prep-TLC (PE / EA 1:4) to afford (ls,3s)-3-(2-(2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-7-((4-fluoro-3-(methylcarbamoyl)phenyl)carbamoyl)-5-methyl-lH-pyrrolo[2,3-c]pyridin-l-yl)ethoxy)cyclobutyl 4-nitrobenzenesulfonate (110 mg, 95%) as a yellow solid. LCMS (ESI, m / z): 813.3 [M+H]+.Step 4:

[0340] To a solution of (ls,3s)-3-(2-(2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-7-((4-fluoro-3 -(methylcarbamoyl)phenyl)carbamoyl)-5 -methyl- IH-pyrrolo [2,3 -c]pyridin- 1 -yl)ethoxy)cyclobutyl 4-nitrobenzenesulfonate (110 mg, 0.14 mmol) and (R)-3-(2,6-difluoro-4-(piperidin-4-yl)phenyl)piperidine-2, 6-dione (125 mg, 0.41 mmol) in MeCN (5 mb) was added Na2COs (72 mg, 0.68 mmol) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for 3 days at 80°C. The resulting mixture was diluted with DMSO (3 mb). The resulting mixture was filtered, and the filter cake was washed with DCM and MeCN. The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on C18 silica with MeCN in water (0.1% FA) to afford the racemic product. The racemate was further resolved by Chiral-HPLC (Column: CHIRALPAKWSGR Docket No. 66412-753.601IK, 5 pm, 20 mm*250 mm; Mobile Phase A: EtOH: DCM=1: 1, Mobile Phase B: Hex (with 0.5% NH3 (2 M in MeOH)); Flow rate: 20 mL / min; Gradient (B%)30% B; Wave Length: 220 / 254 nm; RTl(min): 5.99; RT2(min): 7.37) to afford (R)-3-(2,6-difluoro-4-(piperidin-4-yl)phenyl)piperidine-2, 6-dione (Peak 1, 14.5 mg, 98.7%). LCMS (ESI, m / z): 918.3 [M+H]+. ’HNMR(400 MHz, DMSO-de) 5 10.94 (s, 1H), 10.89 (s, 1H), 8.27 (s, 1H), 8.25 - 8.13 (m, 2H), 8.05 - 7.94 (m, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H), 7.63 (s, 1H), 7.33 (t, J = 9.6 Hz, 1H), 6.99 (d, J = 17.2 Hz, 2H), 6.70 (s, 1H), 4.62 (t, J = 4.8 Hz, 2H), 4.19 (dd, J = 12.8, 5.2 Hz, 1H), 3.48 (s, 3H), 3.27 - 3.12 (m, 2H), 2.80 (d, J = 4.4 Hz, 3H), 2.74 - 2.66 (m, 2H), 2.63 (s, 3H), 2.61 - 2.55 (m, 1H), 2.50 (s, 3H), 2.45 - 2.38 (m, 2H), 2.19 - 2.08 (m, 2H), 2.06 - 1.92 (m, 2H), 1.76 - 1.62 (m, 4H), 1.61 - 1.42 (m, 6H).Step 1:

[0341] A solution of l-(2-((l-(tert-butoxycarbonyl)azetidin-3-yl)oxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo- 2,3-dihydroisoxazol-4-yl)phenyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylic acid (2 g, 3.55 mmol) in DMF (15 mb) was treated with 5-amino-2-fluoro-N-(l-methyl-lH-pyrazol-3-yl)benzamide (1.08 g, 4.62 mmol), DIEA (2.30 g, 17.77 mmol) at room temperature for 10 min under nitrogen atmosphere followed by the addition of HATU (2.03 g, 5.33 mmol) in portions at 0 °C. The resulting mixture was stirred at room temperature for 1 h under nitrogen atmosphere. The reaction mixture was directly purified by flash column chromatography on C18 silica with MeCN in water (10 mM NH4HCO3) to afford tert-butyl 3-(2-(2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-7-((4-fluoro-3-((l- methyl-lH-pyrazol-3-yl)carbamoyl)phenyl)carbamoyl)-5-methyl-lH-pyrrolo[2,3-c]pyridin-l- yl)ethoxy)azetidine-l -carboxylate (2 g, 72.2% yield, 95% purity) as a yellow solid. LCMS (ESI, m / z): 779.3 [M+H]+.WSGR Docket No. 66412-753.601Step 2:

[0342] A solution of tert-butyl 3-(2-(2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-7-((4-fluoro-3-((l-methyl-lH-pyrazol-3-yl)carbamoyl)phenyl)carbamoyl)-5-methyl-lH-pyrrolo[2,3-c]pyridin-l-yl)ethoxy)azetidine-l -carboxylate (1.3 g, 1.67 mmol) and TFA (4 mb) in DCM (20 mb) was stirred at room temperature for 1 h under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The crude product was used in the next step directly without further purification.LCMS (ESI, m / z): 679.3 [M+H]+.Step 3:

[0343] To a stirred solution of l-(2-(azetidin-3-yloxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-N-(4-fluoro-3-((l-methyl-lH-pyrazol-3-yl)carbamoyl)phenyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (1 g, 1.47 mmol) and DIEA (0.57 g, 4.42 mmol) in DMF (15 mb) were added HATU (0.84 g, 2.21 mmol) and (R)-l-(4-(2,6-dioxopiperidin-3-yl)-3,5-difluorophenyl)piperidine-4-carboxylic acid (0.62 g, 1.77 mmol,) in portions at room temperature under air atmosphere. The resulting mixture was stirred at room temperature for 1 h under air atmosphere. The reaction mixture was concentrated under reduced pressure and the residue was purified by flash column chromatography on C18 silica with MeCN in water (0.1% FA) and further purified Prep-HPLC (Column: X-Select Prep OBD C18 Column, 30* 150 mm, 5 pm; Mobile Phase A: Water (0.1% FA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient (B%): 33% B to 58% B in 10 min; Wave Length: 254 nm / 220 nm; RTl(min): 7.55) to afford (R)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-((l-(l-(4-(2,6-dioxopiperidin-3-yl)-3,5-difluorophenyl)piperidine-4-carbonyl)azetidin-3-yl)oxy)ethyl)-N-(4-fluoro-3 -(( 1 -methyl- lH-pyrazol-3 -yl)carbamoyl)phenyl)-5 -methyl- IH-pyrrolo [2,3 -c]pyridine-7-carboxamide (605.7 mg, 40.6% yield, 98.5% purity). LCMS (ESI, m / z): 1013.3 [M+H]+. 'HNMR (400 MHz, DMSO-d6) 5 10.95 (s, 1H), 10.87 (s, 1H), 10.78 (s, 1H), 8.16 (dd, J = 6.4, 2.8 Hz, 1H), 8.04 - 7.95 (m, 1H), 7.82 - 7.75 (m, 2H), 7.72 - 7.60 (m, 4H), 7.35 (t, J = 9.2 Hz, 1H), 6.71 (s, 1H), 6.64 - 6.55 (m, 3H), 4.66 - 4.64 (m, 2H), 4.10 - 3.97 (m, 2H), 3.85 (d, J = 10.4 Hz, 1H), 3.81 - 3.65 (m, 6H), 3.49 (s, 3H), 3.43 (dd, J = 9.2, 3.6 Hz, 1H), 3.37 (s, 1H), 3.22 (dd, J = 10.4, 3.6 Hz, 1H), 3.12 - 3.11 (m, 1H), 2.86 - 2.60 (m, 6H), 2.52 - 2.51 (m, 4H), 2.25 - 2.16 (m, 1H), 2.09 -2.07 (m, 1H), 2.01 - 1.93 (m, 1H), 1.46 - 1.44 (m, 4H).WSGR Docket No. 66412-753.601Example 146NH2step 1Step 1:

[0344] A solution of l-(2-((l-(tert-butoxycarbonyl)azetidin-3-yl)oxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylic acid (300 mg, 0.53 mmol) and 5 -amino-2 -fluorobenzamide (164 mg, 1.06 mmol) in DMF (10 mL) was treated with DIEA (206 mg, 1.59 mmol) and HATU (304 mg, 0.80 mmol) at room temperature for 1 h under nitrogen atmosphere. The reaction mixture was directly purified by flash column chromatography on C18 silica with MeCN in water (0.1% FA) to afford tert-butyl 3-(2-(7-((3-carbamoyl-4-fluorophenyl)carbamoyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-5-methyl-lH-pyrrolo[2,3-c]pyridin-l-yl)ethoxy)azetidine-l -carboxylate (350 mg, 93.9% yield, 90% purity) as a yellow oil. LCMS (ESI, m / z): 699.2 [M+H]+.Step 2:

[0345] A solution of tert-butyl 3-(2-(7-((3-carbamoyl-4-fluorophenyl)carbamoyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-5-methyl-lH-pyrrolo[2,3-c]pyridin-l-yl)ethoxy)azetidine-l-carboxylate (350 mg, 0.50 mmol) in DCM (3 mL) was treated with TFA (3 mL) at room temperature for 2 h under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The residue was basified with saturated aqueous NaHCOs (20 mL). The aqueous layer was extracted with DCM (3 x 50 mL). The organic extracts were combined and concentrated under reduced pressure to afford l-(2-(azetidin-3-yloxy)ethyl)-N-(3-carbamoyl-4-fluorophenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (250 mg, 83.4% yield, 95% purity) as a light yellow solid. LCMS (ESI, m / z): 599.2 [M+H]+.Step 3:

[0346] A solution of l-(2-(azetidin-3-yloxy)ethyl)-N-(3-carbamoyl-4-fluorophenyl)-2-(4-(2,5-dimethyl-3 -oxo-2, 3 -dihydroisoxazol-4-yl)phenyl)-5 -methyl- lH-pyrrolo[2, 3 -c]pyridine-7 -carboxamide (150 mg, 0.25 mmol) and 3-(2,6-difluoro-4-(4-oxopiperidin-l-yl)phenyl)piperidine-2, 6-dione (121 mg, 0.37 mmol) in MeOH (3 mL) and DCM (3 mL) was treated with AcONa (41 mg, 0.50 mmol) and HO Ac (75 mg, 1.25 mmol) at room temperature for 30 min under air atmosphere followed by the addition of NaBHsCN (23 mg, 0.37 mmol) at 25 °C. The resulting mixture was stirred at room temperature for 2h. The reactionWSGR Docket No. 66412-753.601mixture was concentrated under vacuum, The residue was purified by Prep-TLC (DCM / MeOH, 10: 1) to afford N-(3-carbamoyl-4-fluorophenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-((l-(l-(4-(2,6-dioxopiperidin-3-yl)-3,5-difluorophenyl)piperidin-4-yl)azetidin-3-yl)oxy)ethyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (160 mg, 70.6% yield, 95% purity) as a light yellow solid. LCMS (ESI, m / z): 905.3 [M+H]+.Step 4:

[0347] N-(3-carbamoyl-4-fluorophenyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-(( 1 -( 1 -(4-(2,6-dioxopiperidin-3 -y 1) -3,5 -difluorophenyl)piperidin-4-yl)azetidin-3 -yl)oxy)ethyl)-5 -methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (160 mg ) was purified by Chiral-HPLC (Column: (R, R)-Whelk-01, 5 pm, 21.1 mm 250 mm; Mobile Phase A: MeOH: DCM=1: 1, Mobile Phase B: Hex (with 0.5% NHs (2 M in MeOH)); Flow rate: 20 mL / min; Gradient (B%) 35% B; Wave Length: 220 / 254 nm; RTl(min): 15.68; RT2(min): 18.99) to afford (R)-N-(3-carbamoyl-4-fluorophenyl)-2-(4-(2,5-dimethyl-3-oxo-2, 3 -dihydroisoxazol-4-yl)phenyl)- 1 -(2-(( 1 -( 1 -(4-(2,6-dioxopiperidin-3 -y 1) -3,5 -difluorophenyl)piperidin-4-yl)azetidin-3-yl)oxy)ethyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (Peak 2, 46.2 mg, 27.2% yield, 97.7% purity). LCMS (ESI, m / z): 905.4 [M+H]+. 'H NMR (400 MHz, DMSO-d6) 5 10.89 (s, 1H), 10.88 (s, 1H), 8.24 - 8.20 (m, 1H), 8.03 - 7.95 (m, 1H), 7.79 (d, J = 8.0 Hz, 2H), 7.72 (s, 1H), 7.70 (s, 1H), 7.67 (d, J = 8.0 Hz, 2H), 7.63 (s, 1H), 7.33 (dd, J = 12.0, 8.0 Hz, 1H), 6.71 (s, 1H), 6.57 (d, J = 12.0 Hz, 2H), 4.60 (t, J = 5.6 Hz, 2H), 4.04 (dd, J = 12.0, 4.0 Hz, 1H), 3.62 - 3.54 (m, 1H), 3.53 - 3.43 (m, 6H), 3.25 (t, J = 5.6 Hz, 2H), 3.12 (t, J = 6.4 Hz, 2H), 2.85 - 2.68 (m, 3H), 2.63 (s, 3H), 2.49 (s, 3H), 2.30 - 2.22 (m, 2H), 2.15 - 2.01 (m, 1H), 2.00 - 1.90 (m, 1H), 1.8. - 1.73 (m, 1H), 1.51 - 1.39 (m, 2H), 1.06 - 0.93 (m, 2H).Example 205WSGR Docket No. 66412-753.601Step 1:

[0348] To a solution of methyl 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-5 -methyl -lH-pyrrolo[2,3-c]pyridine-7-carboxylate (3 g, 7.95 mmol) and Cs2CO3(7.8 g, 23.8 mmol) in DMF (40 mL) was added (((lr,3r)-3-(2-bromoethoxy)cyclobutoxy)methyl)benzene (3.4 g, 11.9 mmol). The resulting mixture was stirred at 80 °C for 3 h under a nitrogen atmosphere. The reaction mixture was filtered, and the filter cake was washed with EtOAc. The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on C18 silica with MeCN in water (0.1% FA) to afford methyl l-(2-((lr,3r)-3-(benzyloxy)cyclobutoxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (3 g, 64% yield) as a yellow oil. LCMS (ESI, m / z): 581.7 [M+H]+.Step 2:

[0349] To a solution of methyl l-(2-((lr,3r)-3-(benzyloxy)cyclobutoxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (3 g, 5.16 mmol) in AcOH (30 mL) was added Pd / C (10% w / w, 3 g) under nitrogen atmosphere. The mixture was hydrogenated at room temperature for 3 h under a hydrogen balloon. The reaction mixture was filtered through a celite pad and the filtrate was concentrated under reduced pressure to afford methyl 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-((lr,3r)-3-hydroxycyclobutoxy)ethyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (3 g, crude product) as a yellow oil. LCMS (ESI, m / z): 491.5 [M+H]+.Step 3:

[0350] To a solution of methyl 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-((lr,3r)-3-hydroxycyclobutoxy)ethyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylate (3 g, 6.10 mmol) in THF (30 mL) and H2O (10 mL) was added LiOH·H2O (1.28 g, 30.5 mmol). The resulting mixture was stirred at 50 °C for 2 h. The mixture was acidified with HCl (4 M) and concentrated under reduced pressure. The residue was purified by flash column chromatography on C18 silica with MeCN in water (0.1% FA) to afford 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-((lr,3r)-3-hydroxycyclobutoxy)ethyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylic acid (1.9 g, 65% yield) as a yellow solid. LCMS (ESI, m / z): 477.5 [M+H]+.Step 4:

[0351] To a solution of 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-((lr,3r)-3-hydroxycyclobutoxy)ethyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylic acid (600 mg, 1.25 mmol), 2-fluoro-6-methylpyridin-3-amine (238 mg, 1.88 mmol) in DMF (5 mL) were added TCFH (529 mg, 1.88 mmol) and 1 -methyl- IH-imidazole (309 mg, 3.76 mmol). The resulting solution was stirred for 1 h at room temperature. The reaction mixture was directly purified by flash column chromatography on C18 silica with MeCN in water (0.1% FA) to afford 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-N-(2-fluoro-6-methylpyridin-3-yl)-1-(2-((1r,3r)-3-hydroxycyclobutoxy)ethyl)-5-methyl-1H-pyrrolo[2,3-c]pyridine-7-carboxamide (450 mg, 61% yield) as a yellow solid. LCMS (ESI, m / z): 585.6 [M+H]+.WSGR Docket No. 66412-753.601Step 5:

[0352] To a solution of 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-N-(2-fluoro-6-methylpyridin-3 -yl) - l-(2-((lr,3r)-3 -hydroxycyclobutoxy)ethyl) -5 -methyl- 1 H-pyrrolo [2, 3 -c] pyridine -7-carboxamide (440 mg, 0.75 mmol) in DCM (2.5 mL) and DMSO (2.5 mL) was added TEA (380 mg, 3.75 mmol). After 5 minutes, sulfur trioxide pyridine complex (358 mg, 2.25 mmol) was added. The mixture was stirred at 50 °C for 4 days. The reaction was then quenched with water and extracted with DCM. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel with petrol ether / EtOAc (1 / 9) to afford 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-N-(2-fluoro-6-methylpyridin-3-yl)-5-methyl-l-(2-(3-oxocyclobutoxy)ethyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (320 mg, 73% yield) as a yellow solid. LCMS (ESI, m / z): 583.6 [M+H]+.Step 6:

[0353] To a solution of 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-N-(2-fluoro-6-methylpyridin-3-yl)-5-methyl-l-(2-(3-oxocyclobutoxy)ethyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (160 mg, 0.27 mmol), 3-(l-methyl-6-(piperidin-4-yl)-lH-indazol-3-yl)piperidine-2, 6-dione (107 mg, 0.33 mmol) in DCM (3 mL) and MeOH (0.6 mL) were added AcONa (112 mg, 1.37 mmol) and AcOH (33 mg, 0.55 mmol). After 30 min, NaBH3CN (51 mg, 0.82 mmol) was added. The reaction mixture was stirred at room temperature for 16 h under nitrogen atmosphere. The reaction was quenched with saturated aqueous NH4CI at room temperature and was extracted with DCM. The combined organic layers were dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on C18 silica with MeCN in water (0.1% FA) to afford a yellow solid. The solid was further purified by Prep-HPLC (Column: XBridge Prep OBD C18 Column, 30*75 mm, 3.5 pm; Mobile Phase A: Water(10 mmol / LNH4HCO3+0.05% NH3·H2O), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient (B%): 49% B to 74% B in 6 min; Wave Length: 254 nm / 220 nm; RTl(min): 5.01). The product was concentrated under reduced pressure and lyophilized to afford 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-l-(2-((ls,3s)-3-(4-(3-(2,6-dioxopiperidin-3-yl)- 1 -methyl- lH-indazol-6-yl)piperidin- 1 -yl)cyclobutoxy)ethyl)-N-(2-fluoro-6-methylpyridin-3-yl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (28.1 mg, 11%). LCMS (ESI, m / z): 894.4 [M+H]+. 'H NMR (400 MHz, DMSO-d6) 5 10.88 (s, 1H), 10.58 (s, 1H), 8.38 (dd, J = 10.0, 8.0 Hz, 1H), 7.79 (d, J = 8.0 Hz, 2H), 7.74 - 7.65 (m, 3H), 7.60 (d, J = 8.4 Hz, 1H), 7.41 (s, 1H), 7.29 (d, J = 8.0 Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H), 6.73 (s, 1H), 4.69 (t, J = 5.6 Hz, 2H), 4.33 (dd, J = 9.6, 5.2 Hz, 1H), 3.96 (s, 3H), 3.47 (s, 3H), 3.30 - 3.21 (m, 3H), 2.74 - 2.56 (m, 8H), 2.50 (s, 3H), 2.43 (s, 3H), 2.40 -2.28 (m, 1H), 2.21 -2.11 (m, 1H), 2.10 - 2.00 (m, 3H), 1.78 - 1.57 (m, 6H), 1.28 - 1.13 (m, 2H).WSGR Docket No. 66412-753.601Example 249Step 1:

[0354] To a solution of l-(2-((l-(tert-butoxycarbonyl)piperidin-4-yl)oxy)ethyl)-2-(4-(2,5-dimethyl-3-oxo-2, 3-dihydroisoxazol-4-yl)phenyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxylic acid (200 mg, 0.33 mmol) in DMF (5 mL) were added DIEA (220 mg, 1.7 mmol) and HATU (193 mg, 0.51 mmol) at room temperature under nitrogen atmosphere. The mixture was stirred at room temperature for 5 minutes under nitrogen atmosphere. Then added 5-amino-2-fluoro-N-(1-methyl-1H-pyrazol-3-yl)benzamide (158 mg, 0.67 mmol) at room temperature. The resulting solution was stirred at room temperature for 1 h under nitrogen atmosphere. The resulting solution was purified by flash column chromatography on C18 silica with water (0.5% TFA) / MeCN to afford tert-butyl 4-(2-(2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-7-((4-fluoro-3-((l-methyl-lH-pyrazol-3-yl)carbamoyl)phenyl)carbamoyl)-5-methyl-lH-pyrrolo[2,3-c]pyridin-l-yl)ethoxy)piperidine-l-carboxylate (250 mg, 91% yield) as a yellow solid. LCMS (ESI, m / z): 807.3 [M+H]+.Step 2:

[0355] To a solution of tert-butyl 4-(2-(2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-7-((4-fluoro-3-((l-methyl-lH-pyrazol-3-yl)carbamoyl)phenyl)carbamoyl)-5-methyl-lH-pyrrolo[2,3-c]pyridin-l-yl)ethoxy)piperidine-l -carboxylate (250 mg, 0.31 mmol) in DCM (3 mL), was added TFA (1 mL) at room temperature under nitrogen atmosphere. The resulting solution was stirred at room temperature for 2 h under nitrogen atmosphere. The solution mixture was concentrated under vacuum. The crude product was diluted with DCM and basified to pH 8 with NaHCOs(aq.). The mixture was extracted with DCM. The combined organic extracts were washed with water and brine, dried overWSGR Docket No. 66412-753.601anhydrous Na2SC>4 and concentrated under vacuum to afford 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-N-(4-fluoro-3-((l-methyl-lH-pyrazol-3-yl)carbamoyl)phenyl)-5-methyl-l-(2-(piperidin-4-yloxy)ethyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (200 mg, 91% yield) as a yellow solid. LCMS (ESI, m / z): 707.3 [M+H]+.Step 3:

[0356] To a solution of 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)-N-(4-fluoro-3-((l-methyl-lH-pyrazol-3-yl)carbamoyl)phenyl)-5-methyl-l-(2-(piperidin-4-yloxy)ethyl)-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (140 mg, 0.19 mmol) and 3-[2,6-difluoro-4-(3-oxoazetidin-l-yl)phenyl]piperidine-2, 6-dione (174 mg, 0.59 mmol) in DCM (3 mL), were added STAB (125 mg, 0.59 mmol) at room temperature under nitrogen atmosphere. The resulting solution was stirred at room temperature overnight under nitrogen atmosphere. The resulting solution was purified by flash column chromatography on C18 silica with water (0.5% FA) / MeCN to afford 2-(4-(2,5-dimethyl-3-oxo-2,3-dihydroisoxazol-4-yl)phenyl)- 1 -(2-(( 1 -( 1 -(4-(2,6-dioxopiperidin-3 -y 1) -3,5 -difluorophenyl)azetidin-3 -yl)piperidin-4-yl)oxy)ethyl)-N-(4-fluoro-3-((l-methyl-lH-pyrazol-3-yl)carbamoyl)phenyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (110 mg, 56% yield) as a white solid. LCMS (ESI, m / z): 985.4 [M+H]+.Step 4:

[0357] 2-(4-(2, 5 -dimethyl -3 -oxo-2,3 -dihydroisoxazol-4-yl)phenyl)- 1 -(2-(( 1 -( 1 -(4-(2,6-dioxopiperidin-3 -yl)-3,5-difluorophenyl)azetidin-3-yl)piperidin-4-yl)oxy)ethyl)-N-(4-fluoro-3-((l-methyl-lH-pyrazol-3-yl)carbamoyl)phenyl)-5-methyl-lH-pyrrolo[2,3-c]pyridine-7-carboxamide (110 mg) was purified by Prep-Chiral (Column: (R, R)-Whelk-Ol, 5 pm, 21.1 mm250 mm; Mobile Phase A: MeOH: DCM=1: 1, Mobile Phase B: Hex (with 0.5% NHs (2 M in MeOH)); Flow rate: 20 mL / min; Gradient (B%): 20% B; Wave Length: 220 / 254 nm; RTl(min): 8.81; RT2(min): 11.01. The pure fractions were combined and concentrated under vacuum to remove organic solvents. The residual aqueous solution was lyophilized overnight to afford Example 249 (2ndpeak, 14.7 mg). LCMS (ESI, m / z): 985.4 [M+H]+. 'H NMR (400 MHz, DMSO-d6) 5 10.93 (s, 1H), 10.85 (s, 1H), 10.78 (s, 1H), 8.17 - 8.15 (m, 1H), 7.93 - 7.86 (m, 1H), 7.77 (d, J = 8.4 Hz, 2H) 7.68 (d, J = 8.4 Hz, 2H), 7.63 - 7.62 (m, 2H), 7.35 (t, J = 9.2 Hz, 1H), 6.71 (s, 1H), 6.59 (d, J = 2.4 Hz, 1H), 6.06 (d, J = 11.2 Hz, 2H), 4.60 (t, J = 5.2 Hz, 2H), 4.03 (dd, J = 12.4, 5.2 Hz, 1H), 3.80 - 3.77 (m, 5H), 3.49 (s, 3H), 3.48 - 3.44 (m, 2H), 3.37 - 3.33 (m, 2H), 3.03 - 2.98 (m, 1H), 2.92 - 2.85 (m, 1H), 2.82 - 2.73 (m, 1H), 2.62 (s, 3H), 2.51 - 2.49 (m, 4H), 2.18 - 2.08 (m, 3H), 1.98 - 1.87 (m, 1H), 1.75 - 1.74 (m, 2H), 1.45 - 1.39 (m, 2H), 1.13 - 1.08 (m, 2H).

[0358] The following examples were synthesized as described in one of the examples above.Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+3 927.3 10.63 (s, 1H), 8.71 (t, J = 7.8 Hz, 1H), 8.32 (d, J = 5.2 Hz, 1H), 7.85 - 7.80 (m,2H), 7.75 - 7.73 (m, 3H), 7.66 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 7.6 Hz, 3H), 6.71 (s, 2H), 5.93 (s, 1H), 5.23 (dd, J = 13.2, 5.2 Hz, 1H), 5.10 (t, J = 5.6 Hz,2H), 4.58 - 4.27 (m, 2H), 3.61 (s, 3H), 3.56 - 3.54 (m, 2H), 3.47 (t, J = 5.2 Hz,WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+2H), 3.38 - 3.15 (m, 6H), 2.99 - 2.62 (m, 3H), 2.49 (s, 3H), 2.44 - 2.35 (m, 3H), 2.25 - 2.23 (m, 2H), 1.85 - 1.83 (m, 3H)4 854.3 10.88 (s, 1H), 10.82 (s, 1H), 8.39 - 8.28 (m, 3H), 7.98 - 7.93 (m, 2H), 7.81 - 7.75 (m, 3H), 7.71 - 7.70 (m, 2H), 7.63 - 7.61 (m, 1H), 7.48 - 7.43 (m, 1H), 7.38 (s, 1H), 7.17 - 7.10 (m, 4H), 6.80 (s, 1H), 4.67 (t, J = 5.6 Hz, 2H), 3.85 - 3.79 (m, 1H), 3.44- 3.41 (m, 5H), 3.26 - 3.24 (m, 2H), 3.16 - 3.13 (m, 2H), 3.10 - 3.07 (m, 2H), 2.88 - 2.84 (m, 2H), 2.73 - 2.60 (m, 1H), 2.47 - 2.32 (m, 4H), 2.32 - 2.30 (m, 3H), 2.24 - 2.10 (m, 1H), 2.08 - 1.91 (m, 3H), 1.65 - 1.61 (m, 4H)5 855.4 10.90 (s, 1H), 10.78 (s, 1H), 8.42 - 8.26 (m, 2H), 8.01 - 7.94 (m, 2H), 7.85 - 7.76 (m, 3H), 7.71 (d, J = 8.0 Hz, 2H), 7.63 (d, J = 7.7 Hz, 1H), 7.52 - 7.36 (m, 3H), 7.09 (dd, J = 21.5, 8.0 Hz, 3H), 6.93 - 6.77 (m, 3H), 4.68 (t, J = 5.5 Hz, 2H), 3.74 (dd, J= 11.1, 4.9 Hz, 1H), 3.46 (d, J = 14.7 Hz, 5H), 3.22 - 3.15 (m, 2H), 3.13 - 2.99 (m, 5H), 2.65 (d, J = 5.8 Hz, 1H), 2.49 (s, 4H), 2.29 (s, 1H), 2.19 -2.10 (m, 1H), 2.02 (dt, J = 8.2, 4.3 Hz, 1H)6 924.3 11.08 (s, 1H), 10.89 (s, 1H), 8.36 (t, J= 2.0 Hz, 1H), 8.30 (d, J= 5.2 Hz, 1H),8.18 (s, 1H), 8.00 - 7.93 (m, 2H), 7.83 - 7.78 (m, 3H), 7.74 - 7.68 (m, 2H), 7.64 - 7.62 (m, 1H), 7.49 - 7.41 (m, 1H), 7.39 (s, 1H), 7.06 - 6.97 (m, 2H), 6.88 (dd, J= 8.2, 1.6 Hz, 1H), 6.80 (s, 1H), 5.34 (dd, J= 12.8, 5.2 Hz, 1H), 4.67 (t, J= 5.6 Hz, 2H), 3.47 (s, 3H), 3.45 - 3.42 (m, 2H), 3.32 (s, 3H), 3.27 (t, J= 5.6 Hz, 2H), 3.17 - 3.06 (m, 4H), 2.91 - 2.85 (m, 3H), 2.78 - 2.57 (m, 3H), 2.51 - 2.49 (m, 3H), 2.39 - 2.32 (m, 2H), 2.08 - 1.94 (m, 3H), 1.67 - 1.64 (m, 4H)7 882.3 10.98 (s, 1H), 8.61 (d, J = 9.2 Hz, 1H), 8.33 (d, J = 5.2 Hz, 1H), 7.83 - 7.79 (m, 2H), 7.77 - 7.69 (m, 3H), 7.65 (d, J = 8.0 Hz, 2H), 7.46 - 7.39 (m, 2H), 7.33 (d, J = 8.0 Hz, 1H), 7.18 (d, J = 8.0 Hz, 1H), 6.72 (s, 1H), 5.23 (dd, J = 13.2, 5.2 Hz, 1H), 5.02 (t, J = 5.2 Hz, 2H), 4.48 (d, J = 17.2 Hz, 1H), 4.35 (d, J = 17.2 Hz, 1H), 3.65 - 3.64 (m, 2H), 3.61 (s, 2H), 3.53 - 3.51 (s, 2H), 3.40 (t, J = 5.2 Hz, 2H), 3.26 - 3.24 (m, 2H), 3.17 - 3.14 (m, 2H), 2.98 - 2.81 (m, 3H), 2.73 - 2.70 (m, 7H), 2.49 (s, 3H), 2.43 - 2.24 (m, 5H), 1.94 - 1.90 (m, 2H) 8 881.4 10.98 (s, 1H), 10.91 (s, 1H), 8.88 (d, J = 2.4 Hz, 1H), 8.30 (d, J = 5.2 Hz, 1H),8.16 (dd, J = 8.4, 2.4 Hz, 1H), 7.82 - 7.77 (m, 3H) 7.71 (d, J = 8.4 Hz, 2H), 7.64 (d, J = 8.0 Hz, 2H), 7.44 (s, 1H), 7.38 - 7.33 (m, 1H), 7.28 (d, J = 8.4 Hz, 1H), 6.80 (s, 1H), 5.11 (dd, J = 13.2, 5.2 Hz, 1H), 4.67 (t, J = 5.2 Hz, 2H), 4.42 (d, J = 17.2 Hz, 1H), 4.29 (d, J = 17.2 Hz, 1H), 3.48 (s, 3H), 3.42 (t, J = 5.2 Hz, 2H), 3.26 (t, J = 5.6 Hz, 2H), 3.17 - 3.15 (m, 2H), 3.10 - 3.07 (m, 2H), 2.94 - 2.86 (m, 3H), 2.68 - 2.58 (m, 3H), 2.52 - 2.50 (m, 1H), 2.45 (s, 3H), 2.42 - 2.32 (m, 3H), 2.03 - 1.95 (m, 3H), 1.71 - 1.56 (m, 4H)9 865.3 10.96 (d, J = 21.4 Hz, 2H), 8.38 (s, 1H), 8.30 (d, J = 5.3 Hz, 1H), 8.19 (s, 1H),7.98 (d, J = 9.1 Hz, 2H), 7.84 - 7.76 (m, 3H), 7.73 (d, J = 7.9 Hz, 2H), 7.63 (d, J = 7.8 Hz, 2H), 7.46 (t, J = 7.8 Hz, 1H), 7.40 (s, 2H), 7.32 (d, J = 7.8 Hz, 1H), 6.82 (s, 1H), 5.11 (dd, J = 13.2, 5.2 Hz, 1H), 4.69 (s, 2H), 4.42 (d, J = 17.2 Hz, 1H), 4.29 (d, J = 17.3 Hz, 1H), 3.48 (s, 3H), 3.09 (d, J = 5.8 Hz, 4H), 2.59 (s, 4H), 2.15 (s, 3H), 2.01 (s, 2H), 1.79 (t, J = 11.2 Hz, 3H), 1.56 (s, 2H), 1.47 (d, J = 12.2 Hz, 2H), 1.24 (s, 1H), 0.86 (s, 1H)10 891.5 10.98 (s, 1H), 10.92 (s, 1H), 8.39 (t, J = 2.0 Hz, 1H), 8.32 (d, J = 5.2 Hz, 1H),8.03 - 8.01 (m, 1H), 7.97 (s, 1H), 7.86 - 7.78 (m, 3H), 7.74 - 7.66 (m, 2H), 7.66 - 7.63 (m, 2H), 7.51 - 7.42 (m, 2H), 7.41 - 7.33 (m, 2H), 6.83 (s, 1H), 5.10 (dd, J = 13.2, 5.2 Hz, 1H), 4.71 (t, J = 5.6 Hz, 2H), 4.42 (d, J = 17.2 Hz, 1H), 4.28 (d, J = 17.2 Hz, 1H), 3.52 - 3.51 (m, 1H), 3.49 (s, 3H), 3.26 (t, J = 5.6 Hz, 2H), 2.93 - 2.90 (m, 1H), 2.77 - 2.66 (m, 2H), 2.62 - 2.61 (m, 1H), 2.44 - 2.30 (m, 2H), 2.05 - 1.94 (m, 1H), 1.68 (d, J = 7.6 Hz, 4H), 1.56 - 1.48(m, 6H), 1.26 - 1.23 (m, 3H), 0.88 - 0.80 (m, 1H)WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+11 891.5 10.98 (s, 1H), 10.92 (s, 1H), 8.39 (t, J = 2.0 Hz, 1H), 8.32 (d, J = 5.2 Hz, 1H),8.03-8.01 (m, 1H), 7.97 (s, 1H), 7.86 - 7.78 (m, 3H), 7.74 - 7.66 (m, 2H), 7.66 - 7.63 (m, 2H), 7.51 - 7.42 (m, 2H), 7.41 - 7.33 (m, 2H), 6.82 (s, 1H), 5.10 (dd, J = 13.2, 5.2 Hz, 1H), 4.65 (t, J = 5.6 Hz, 2H), 4.42 (d, J = 17.2 Hz, 1H), 4.28 (d, J = 17.2 Hz, 1H), 3.48 (s, 3H), 3.26 (t, J = 5.6 Hz, 2H), 2.93 - 2.90 (m, 1H), 2.77 - 2.66 (m, 2H), 2.62 - 2.61 (m, 1H), 2.44 - 2.30 (m, 2H), 2.05 - 1.94 (m, 1H), 1.68 (d, J = 7.6 Hz, 4H), 1.56 - 1.48 (m, 6H), 1.26 - 1.23 (m, 3H)12 923.4 11.65 (s, 1H), 10.40 (s, 1H), 8.35 - 8.24 (m, 2H), 8.08 - 7.95 (m, 2H), 7.82 (d,J = 7.6 Hz, 1H), 7.75 - 7.72 (m, 3H), 7.64 (d, J = 8.0 Hz, 2H), 7.59 (d, J = 7.6 Hz, 1H), 7.48 (t, J = 8.0 Hz, 1H), 7.41 (s, 1H), 7.32 (s, 1H), 6.84 (s, 1H), 6.72 (s, 1H), 5.22 (dd, J= 13.2, 4.8 Hz, 1H), 5.11 - 5.09 (m, 2H), 4.49 - 4.34 (m, 2H), 3.76 - 3.74 (m, 2H), 3.72 - 3.71 (m, 1H), 3.64 (s, 2H), 3.43 (s, 2H), 3.32 - 3.31 (m, 2H), 3.28 - 3.26 (m, 2H), 3.20 - 2.17 (m, 3H), 3.04 - 3.03 (m, 2H), 3.00 - 2.99 (m, 1H), 2.92 - 2.82 (m, 4H), 2.79 - 2.75 (m, 1H), 2.44 - 2.42 (m, 2H), 2.41 - 2.37 (m, 1H), 1.89 - 1.87 (m, 2H), 1.86 - 1.84 (m, 7H)13 910.4 8.37 - 8.28 (m, 2H), 8.00 - 7.94 (m, 1H), 7.81 - 7.73 (m, 3H), 7.71 - 7.67 (m,2H), 7.63 - 7.60 (m, 1H), 7.53 - 7.49 (m, 1H), 7.48 - 7.42 (m, 1H), 7.02 - 7.00 (m, 2H), 6.80 (s, 1H), 5.03 (dd, J = 13.2, 5.2 Hz, 1H), 4.68 - 4.65 (m, 2H), 4.33 (d, J = 16.8 Hz, 1H), 4.21 (d, J = 16.8 Hz, 1H), 3.30 - 3.25 (m, 2H), 3.19 - 3.14 (m, 6H), 3.09 - 3.04 (m, 2H), 2.94 - 2.85 (m, 2H), 2.71 - 2.59 (m, 3H), 2.51 - 2.48 (m, 4H), 2.47 - 2.40 (m, 5H), 2.35 - 2.32 (m, 3H), 2.00 - 1.95 (m, 1H)14 927.5 10.97 (d, J = 11.3 Hz, 2H), 8.30 (d, J = 5.3 Hz, 1H), 8.21 (dd, J = 6.5, 2.8 Hz,1H), 7.97 - 7.92 (m, 1H), 7.84 - 7.62 (m, 8H), 7.44 - 7.29 (m, 3H), 6.81 (s, 1H), 5.11 (dd, J = 13.3, 5.1 Hz, 1H), 4.70 - 4.63 (m, 2H), 4.44 - 4.27 (m, 2H), 3.48 - 3.40 (m, 7H), 3.21 - 3.18 (m, 2H), 3.12 - 3.09 (m, 2H), 3.05 - 3.00 (m, 2H), 2.98 - 2.87 (m, 1H), 2.69 - 2.57 (m, 3H), 2.56 - 2.52 (m, 3H), 2.43 - 2.33 (m, 2H), 2.30 - 2.14 (m, 2H), 2.04 - 1.96 (m, 1H), 1.78 - 1.59 (m, 4H) 15 923.4 10.98 (s, 1H), 10.80 (s, 1H), 8.32 (d, J = 2.4 Hz, 1H), 8.15 (d, J = 2.4 Hz, 1H),7.98 - 7.96 (m, 2H), 7.78 - 7.75 (m, 2H), 7.70 - 7.66 (m, 2H), 7.64 - 7.59 (m, 3H), 7.49 - 7.33 (m, 4H), 6.68 (s, 1H), 5.10 (dd, J = 13.2, 5.2 Hz, 1H), 4.61 (t, J = 5.6 Hz, 2H), 4.41 (d, J = 17.2 Hz, 1H), 4.28 (d, J = 17.2 Hz, 1H), 3.47 (s, 3H), 3.44 - 3.39 (m, 2H), 3.31 - 3.23 (m, 4H), 3.19 - 3.13 (m, 2H), 3.10 - 3.06 (m, 2H), 2.96 - 2.85 (m, 3H), 2.69 - 2.56 (m, 3H), 2.62 (s, 3H), 2.42 - 2.32 (m, 3H), 2.08 - 1.95 (m, 3H), 1.73 - 1.55 (m, 4H)16 950.3 12.31 (s, 1H), 10.98 (s, 1H), 10.71 (s, 1H), 8.33 - 8.31 (m, 2H), 7.97 (t, J = 7.2Hz, 1H), 7.87 - 7.84 (m, 2H), 7.80 - 7.78 (m, 2H), 7.74 - 7.70 (m, 2H), 7.61 (d, J = 8.0 Hz, 1H), 7.38 - 7.36 (m, 1H), 7.35 - 7.31 (m, 2H), 7.28 - 7.12 (m, 2H), 6.82 (s, 1H), 5.10 (dd, J = 13.2, 5.2 Hz, 1H), 4.79 (t, J = 5.2 Hz, 2H), 4.39 (d, J = 17.2 Hz, 1H), 4.25 (d, J = 17.2 Hz, 1H), 3.49 - 3.45 (m, 7H), 3.26 (t, J = 6.0 Hz, 2H), 3.21- - 3.19 (m, 2H), 3.14 - 3.10 (m, 2H), 2.98 - 2.86 (m, 3H), 2.65 -2.52 (m, 2H), 2.41 -2.34 (m, 1H), 2.31 - 2.29 (m, 3H), 1.97 - 1.95 (m, 3H), 1.64 - 1.52 (m, 4H)17 927.8 11.01 (s, 1H), 10.88 (s, 1H), 8.36 (s, 1H), 8.30 (d, J = 5.2 Hz, 1H), 8.01 - 7.95(m, 2H), 7.80 - 7.62 (m, 6H), 7.55 - 7.38 (m, 4H), 6.80 (s, 1H), 5.12 (dd, J = 13.2, 3.2 Hz, 1H), 4.67 (s, 2H), 4.54 (d, J = 17.2 Hz, 1H), 4.37 (d, J = 17.2 Hz, 1H), 3.45 - 3.44 (m, 5H), 3.27 - 3.24 (m, 2H), 3.16 - 3.09 (m, 4H), 2.92 - 2.71 (m, 4H), 2.63 - 2.58 (m, 2H), 2.51 - 2.42 (m, 3H), 2.41 - 2.35 (m, 2H), 2.16 - 1.86 (m, 3H), 1.80 - 1.50 (m,4H)18 890.6 10.97 (s, 1H), 10.87(s, 1H), 8.35 (s, 1H), 8.29 (d, J = 5.2 Hz, 1H), 7.96 - 7.92(m, 2H), 7.81 - 7.77 (m, 3H), 7.70 (d, J = 8.0 Hz, 2H), 7.62 (d, J = 7.6 Hz, 1H), 7.45 (t, J = 8.0 Hz, 1H), 7.39 (s, 1H), 6.97 (d, J = 9.6 Hz, 2H), 6.80 (s,1H), 4.66 (t, J = 5.2 Hz, 2H), 4.22 - 4.17 (m, 1H), 3.47 (s, 3H), 3.43 (t, J = 5.2WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+Hz, 2H), 3.27 (t, J = 5.6 Hz, 2H), 3.16 - 3.17 (m, 2H), 3.08 - 3.06 (m, 2H), 2.90 (s, br, 2H), 2.86 - 2.77 (m, 1H), 2.57 - 2.52 (m, 2H), 2.50 (s, 3H), 2.42 - 2.32 (m, 2H), 2.23 - 2.00 (m, 4H), 1.70 - 1.67 (m, 2H), 1.58 - 1.51 (m, 2H) 21 953.4 10.99 (s, 1H), 10.80 (s, 1H), 8.30 (s, 1H), 7.98 (d, J = 9.4 Hz, 2H), 7.79 (d, J =8.2 Hz, 2H), 7.65 (dd, J = 11.9, 8.0 Hz, 4H), 7.47 (d, J = 8.0 Hz, 1H), 7.41 (s, 2H), 7.33 (d, J = 7.9 Hz, 1H), 7.14 (s, 1H), 6.62 (s, 1H), 5.12 - 5.10 (m, 1H), 4.51 (s, 2H), 4.45 - 4.28 (m, 4H), 3.82 (d, J = 15.3 Hz, 4H), 3.73 - 3.54 (m, 6H), 3.49 (s, 3H), 3.40 (s, 2H), 3.10 (s, 2H), 2.62 (s, 7H), 1.97 (s, 4H), 0.93 (d, J = 7.1 Hz, 3H)22 892.4 10.94 (s, 1H), 10.92 (s, 1H), 8.41 (t, J = 1.6 Hz, 1H), 8.31 (d, J = 5.2 Hz, 1H),8.02 - 7.97 (m, 2H), 7.82 - 7.76 (m, 3H), 7.74 - 7.61 (m, 3H), 7.52 - 7.44 (m, 2H), 7.36 (s, br, 1H), 7.04 - 6.96 (m, 2H), 6.83 (s, 1H), 5.03 (dd, J = 13.2, 5.2 Hz, 1H), 4.70 (t, J = 5.2 Hz, 2H), 4.30 (d, J = 16.8 Hz, 2H), 4.18 (d, J = 16.8 Hz, 2H), 3.64 - 3.61 (m, 3H), 3.48 (s, 3H), 2.81 - 2.75 (m, 4H), 2.60 - 2.55 (m, 6H), 2.51 -2.49 (m, 2H), 2.01 - 1.86 (m, 2H), 1.50 - 1.48 (m, 2H), 1.04- 1.02 (m, 2H)23 904.2 8.37-8.25 (m, 2H), 8.02 - 8.00 (m, 1H), 7.82 - 7.81 (d, J = 5.2 Hz, 1H), 7.77 - 7.75 (m, 2H), 7.67 - 7.62 (m, 4H), 7.51 - 7.46 (m, 2H), 7.38 (d, J = 8.0 Hz, 1H), 6.82 (s, 1H), 5.03 (dd, J = 13.2, 5.2 Hz, 1H), 4.66 - 4.63 (m, 2H), 4.43 (d, J = 17.2 Hz, 1H), 4.29 (d, J = 17.2 Hz, 1H), 3.47 (s, 3H), 3.40 - 3.31 (m, 1H), 3.24 - 3.17 (m, 2H), 2.93 - 2.78 (m, 3H), 2.66 - 2.58 (m, 2H), 2.49 - 2.44 (m, 4H), 2.22 - 1.91 (m, 7H), 1.76- 1.58 (m, 5H), 1.16 - 1.12 (m, 1H), 1.04 - 0.97 (m, 2H)24 909.7 10.92 (s, 1H), 8.38 (t, J = 2.0 Hz, 1H), 8.31 - 8.27 (m, 3H), 8.02 - 7.95 (m,2H), 7.82 - 7.79 (m, 2H), 7.70 (d, J = 8.4 Hz, 2H), 7.64 (d, J = 7.6 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.49 - 7.45 (m, 2H), 7.38 (s, 1H), 6.82 (s, 1H), 5.11 (dd, J = 13.2, 5.2 Hz, 1H), 4.69 (t, J = 5.6 Hz, 2H), 4.54 (d, J = 17.2 Hz, 1H), 4.36 (d, J = 17.2 Hz, 1H), 3.52 - 3.51 (m, 1H), 3.48 (s, 3H), 3.26 (t, J = 5.6 Hz, 2H), 2.99 - 2.85 (m, 1H), 2.84 - 2.76 (m, 1H), 2.72 - 2.56 (m, 3H), 2.53 (s, 3H), 2.41 - 2.38 (m, 2H), 2.05 - 1.95 (m, 1H), 1.71 - 1.48 (m, 10H)25 909.3 11.0 (s, 1H), 10.92 (s, 1H), 8.39 (t, J= 2.0 Hz, 1H), 8.30 (d, J= 5.2 Hz, 1H),8.00 - 7.95 (m, 2H), 7.83 - 7.80 (m, 3H), 7.71 - 7.68 (m, 2H), 7.66 - 7.62 (m, 1H), 7.55 (d, J= 7.6 Hz, 1H), 7.53 - 7.47 (m, 2H), 7.37 (s, 1H), 6.81 (s, 1H), 5.11 (dd, J= 13.2, 5.2 Hz, 1H), 4.65 (t, J= 6.0 Hz, 2H), 4.55 (d, J= 17.2 Hz, 1H), 4.37 (d, J= 17.2 Hz, 1H), 3.48 (s, 3H), 3.28 - 3.24 (m, 3H), 2.99 - 2.85 (m, 1H), 2.85 - 2.75 (m, 1H), 2.69 - 2.62 (m, 3H), 2.59 (s, 3H), 2.45 - 2.36 (m, 1H), 2.15 - 1.95 (m, 4H), 1.72- 1.51 (m, 6H), 1.22 - 1.19 (m, 2H) 26 906.5 11.08 (s, 1H), 10.92 (s, 1H), 8.39 (t, J = 2.0 Hz, 1H), 8.32 (d, J = 5.2 Hz, 1H),8.05 - 8.00 (m, 1H), 7.97 (s, 1H), 7.86 - 7.77 (m, 3H), 7.70 (d, J = 8.1 Hz, 2H), 7.64 (d, J = 7.7 Hz, 1H), 7.47 (t, J = 7.9 Hz, 1H), 7.39 (s, 1H), 7.06 (s, 1H), 6.99 (d, J = 8.0 Hz, 1H), 6.88 (d, J = 8.1 Hz, 1H), 6.83 (s, 1H), 5.33 (dd, J = 12.8, 5.4 Hz, 1H), 4.70 (d, J = 6.1 Hz, 2H), 3.32 (s, 3H), 3.26 (t, J = 5.6 Hz, 3H), 3.25 - 3.17 (m, 2H), 2.88 (d, J = 16.5 Hz, 1H), 2.67 (d, J = 23.6 Hz, 4H), 2.49 - 2.33 (m, 2H), 2.06 - 1.93 (m, 2H), 1.98 - 1.76 (m, 2H) 1.56 - 1.41 (m, 10H), 1.24 (s, 2H)27 906.5 11.08 (s, 1H), 10.93 (s, 1H), 8.40 (t, J = 2.0 Hz, 1H), 8.31 (d, J = 5.3 Hz, 1H),8.02 - 7.91 (m, 2H), 7.86 - 7.78 (m, 3H), 7.70 (d, J = 8.3 Hz, 2H), 7.64 (dt, J = 7.8, 1.3 Hz, 1H), 7.46 (t, J = 7.9 Hz, 1H), 7.39 (s, 1H), 7.08 (d, J = 1.5 Hz, 1H), 7.00 (d, J = 8.1 Hz, 1H), 6.89 (dd, J = 8.1, 1.6 Hz, 1H), 6.83 (s, 1H), 5.34 (dd, J = 12.8, 5.4 Hz, 1H), 4.65 (t, J = 6.1 Hz, 2H), 3.48 (s, 3H), 3.30 (s, 3H), 3.23 (s, 3H), 2.91 (s, 2H), 2.71 (s, 1H), 2.68 - 2.59 (m, 4H), 2.51 (s, 1H), 2.50 (s, 1H), 2.06 - 1.95 (m, 4H), 1.61 (d, J = 26.3 Hz, 6H), 1.23 (d, J = 12.8 Hz,2H)WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+28 906.5 11.10 (s, 1H), 10.92 (s, 1H), 8.39 (d, J = 2.0 Hz, 1H), 8.32 (d, J = 5.2 Hz, 1H),8.02 (dd, J = 8.0, 2.2 Hz, 1H), 7.96 (s, 1H), 7.85 - 7.78 (m, 2H), 7.70 (d, J = 8.1 Hz, 1H), 7.64 (d, J = 7.8 Hz, 1H), 7.47 (t, J = 7.9 Hz, 1H), 7.39 (s, 1H), 7.07 - 6.94 (m, 2H), 6.83 (s, 1H), 5.37 (dd, J = 12.6, 5.3 Hz, 1H), 4.71 (t, J = 5.7 Hz, 2H), 3.57 (s, 3H), 3.48 (s, 2H), 3.26 (t, J = 5.7 Hz, 3H), 3.18 (s, 1H), 2.97 - 2.80 (m, 2H), 2.76 -2.71 (m, 1H), 2.60 - 2.59 (m, 1H), 2.48 - 2.31 (m, 4H), 1.99 (d, J = 12.2 Hz, 1H), 1.76 - 1.72 (m, 1H), 1.65- 1.59 (m, 10H), 1.24 (s, 1H)29 906.6 11.05 (s, 1H), 10.94 (s, 1H), 8.40 (t, J = 1.9 Hz, 1H), 8.31 (d, J = 5.2 Hz, 1H),8.03 - 7.93 (m, 2H), 7.86 - 7.76 (m, 3H), 7.75 - 7.68 (m, 2H), 7.64 (dt, J = 7.8, 1.3 Hz, 1H), 7.46 (t, J = 7.9 Hz, 1H), 7.39 (s, 1H), 7.05 - 6.93 (m, 3H), 6.82 (s, 1H), 5.37 (dd, J = 12.6, 5.4 Hz, 1H), 4.65 (t, J = 6.1 Hz, 2H), 3.55 (s, 3H), 3.48 (s, 3H), 3.29 (t, J = 5.9 Hz, 3H), 3.15 (s, 1H), 2.90 (ddd, J = 17.9, 14.3, 5.1 Hz, 1H), 2.79 - 2.57 (m, 4H), 2.32 (s, 4H), 2.01 (dt, J = 11.2, 5.5 Hz, 4H), 1.68 (dt, J = 42.7, 12.1 Hz, 4H), 1.62 - 1.59 (m, 4H), 1.23 (t, J = 4.3 Hz, 2H)32 854.5 10.92 (s, 1H), 10.84 (s, 1H), 8.40 - 8.34 (m, 4H), 8.32 (d, J = 5.2 Hz, 1H), 8.02- 7.98 (m, 1H), 7.96 (s, 1H), 7.83 - 7.78 (m, 3H), 7.76 - 7.62 (m, 4H), 7.46 (t, J = 8.0 Hz, 1H), 7.41-7.36 (m, 1H), 7.25 (t, J = 8.0 Hz, 1H), 7.04 - 6.98 (m, 2H), 6.83 (s, 1H), 4.72 - 4.68 (m, 2H), 3.85 (dd, J = 12.0, 4.8 Hz, 1H), 3.55 - 3.51 (m, 1H), 3.49 (s, 3H), 3.25 (t, J = 5.6 Hz, 2H), 2.72 - 2.60 (m, 4H), 2.50 (s, 3H), 2.40 -2.32 (m, 1H), 2.28 - 2.11 (m, 2H), 2.06 - 1.97 (m, 1H), 1.73 - 1.59 (m, 4H), 1.57 - 1.52 (m, 4H), 1.51 - 1.44 (m, 2H)33 863.7 10.43 (s, 1H), 8.40 (s, 1H), 8.26 (d, J = 5.0 Hz, 2H), 8.02 - 8.00 (m, 1H), 7.90- 7.88 (m, 1H), 7.74 (d, J = 8.0 Hz, 2H), 7.69 (d, J = 5.2 Hz, 1H), 7.62 (d, J = 8.0 Hz, 2H), 7.47 (d, J = 7.6 Hz, 1H), 7.27 - 7.26 (m, 1H), 6.70 - 6.67 (m, 2H), 5.78 (s, 1H), 5.24 (dd, J = 13.2, 5.2 Hz, 1H), 5.12 - 5.10 (m, 2H), 4.57- 4.55 (m, 1H), 4.44 - 4.42 (m, 1H), 4.37 - 3.58 (m, 4H), 3.61 (s, 3H), 3.50 - 3.49 (m, 1H), 3.35 - 3.33 (m, 2H), 3.01 - 2.87 (m, 2H), 2.50 (s, 3H), 2.44 - 2.41 (m, 2H), 2.28 - 2.26 (m, 1H), 1.82 - 1.80 (m, 2H).34 863.4 13.38 - 12.91 (m, 1H), 10.39 (s, 1H), 8.42 - 8.26 (m, 2H), 8.05 - 7.88 (m,3H), 7.74 - 7.72 (m, 3H), 7.63 - 7.60 (m, 3H), 7.51 - 7.44 (m, 2H), 7.25 - 7.24 (m, 1H), 6.72 (s, 1H), 5.22 - 5.05 (m, 3H), 4.55 - 4.30 (m, 4H), 3.99 - 3.98 (m, 1H), 3.75 - 3.73 (m, 1H), 3.63 - 3.55 (m, 5H), 3.30 - 3.28 (m, 2H), 2.95 -2.93 (m, 2H), 2.51 -2.49 (m, 7H), 1.97- 1.95 (m, 2H), 1.61 - 1.48 (m, 3H), 1.27 - 1.25 (m, 1H)35 909.4 10.94 (s, 1H), 10.55 (s, 1H), 8.40 (t, J = 2.0 Hz, 1H), 8.31 (d, J = 5.2 Hz, 1H),8.01 - 7.95 (m, 2H), 7.83 - 7.79 (m, 3H), 7.71 - 7.65 (m, 2H), 7.64 - 7.62 (m, 1H), 7.56 (d, J = 6.0 Hz, 1H), 7.46 (t, J = 8.0 Hz, 1H), 7.39 - 7.33 (m, 2H), 6.82 (s, 1H), 4.64 (t, J = 5.6 Hz, 2H), 4.00 (s, 3H), 3.90 (t, J = 6.8 Hz, 2H), 3.47 (s, 3H), 3.33 - 3.24 (m, 3H), 2.75 (t, J = 6.8 Hz, 3H), 2.67 - 2.65 (m, 2H), 2.51 -2.50 (m, 3H), 2.04 - 1.90 (m, 3H), 1.79- 1.66 (m, 6H), 1.24 - 1.17 (m, 2H)36 915.5 10.87 (s, 1H), 10.86 (s, 1H), 8.34 (t, J = 2.0 Hz, 1H), 8.00 - 7.97 (m, 2H), 7.79- 7.76 (m, 2H), 7.70 - 7.67 (m, 2H), 7.64 - 7.61 (m, 2H), 7.46 (t, J = 8.0 Hz, 1H), 7.40 (s, 1H), 6.71 (s, 1H), 6.15 - 6.12 (m, 2H), 4.65 -4.60 (m, 2H), 4.03 (dd, J = 12.4, 5.2 Hz, 1H), 3.95 (t, J = 8.0 Hz, 2H), 3.81 (t, J = 6.4 Hz, 2H), 3.68 - 3.66 (m, 1H), 3.48 (s, 3H), 3.41 (t, J = 5.2 Hz, 2H), 3.39 - 3.26 (m, 2H), 3.10 - 3.08 (m, 1H), 3.07 - 2.92 (m, 2H), 2.80 - 2.74 (m, 2H), 2.64 (s, 3H), 2.49 (s, 3H), 2.14- 2.01 (m, 1H), 2.00 - 1.90 (m, 1H), 1.50 - 1.31 (m, 2H), 1.10 - 0.97 (m, 2H)37 915.5 10.87 (s, 1H), 10.86 (s, 1H), 8.35 (t, J = 2.0 Hz, 1H), 8.00 - 7.97 (m, 2H), 7.79- 7.76 (m, 2H), 7.70 - 7.67 (m, 2H), 7.64 - 7.61 (m, 2H), 7.46 (t, J = 8.0 Hz,1H), 7.40 (s, 1H), 6.71 (s, 1H), 6.15 - 6.12 (m, 2H), 4.65 -4.61 (m, 2H), 4.03WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+(dd, J = 12.4, 5.2 Hz, 1H), 3.95 (t, J = 8.0 Hz, 2H), 3.81 (t, J = 6.4 Hz, 2H), 3.68 - 3.66 (m 1H), 3.48 (s, 3H), 3.40 (t, J = 5.6 Hz, 2H), 3.32 - 3.29 (m, 2H), 3.15 - 3.10 (m, 1H), 3.09 - 2.92 (m, 2H), 2.81 - 2.74 (m, 2H), 2.63 (s, 3H), 2.49 (s, 3H), 2.15 - 2.01 (m, 1H), 1.98 - 1.90 (m, 1H), 1.50 - 1.20 (m, 2H), 1.10 - 0.97 (m, 2H)38 888.3 11.31 (s, 1H), 10.86 (s, 1H), 8.42 (d, J = 9.2 Hz, 1H), 7.82 - 7.75 (m, 2H), 7.70- 7.65 (m, 4H), 6.77 (s, 1H), 6.15 (d, J = 12.0 Hz, 2H), 4.78 - 4.72 (m, 2H), 4.08 - 4.00 (m, 1H), 3.99 - 3.90 (m, 2H), 3.73 - 3.61 (m, 2H), 3.49 (s, 3H), 3.38 (t, J = 5.6 Hz, 2H), 3.25 - 3.17 (m, 1H), 3.12 - 3.04 (m, 1H), 3.02 - 2.92 (m, 2H), 2.87 - 2.73 (m, 2H), 2.65 (s, 3H), 2.60 (s, 3H), 2.50 - 2.48 (m, 4H), 2.15 - 2.01 (m, 1H), 2.00 - 1.87 (m, 1H), 1.43 - 1.27 (m, 2H), 1.08 - 0.90 (m, 2H)39 905.4 10.98 (s, 1H), 10.83 (s, 1H), 8.34 (t, J = 2.0 Hz, 1H), 8.05 - 8.03 (m, 1H), 7.97(s, 1H), 7.83 - 7.72 (m, 2H), 7.71 - 7.60 (m, 5H), 7.51 - 7.43 (m, 2H), 7.49 - 7.45 (m, 2H), 6.71 (s, 1H), 5.10 (dd, J = 13.2, 5.2 Hz, 1H), 4.65 (t, J = 5.6 Hz, 2H), 4.42 (d, J = 17.2 Hz, 1H), 4.28 (d, J = 17.2 Hz, 1H), 3.52 - 3.48 (m, 4H), 3.47 - 3.33 (m, 2H) 3.24 (t, J = 5.6 Hz, 2H), 2.92 - 2.87 (m, 1H), 2.70 - 2.68 (m, 2H), 2.64 (s, 3H), 2.60 - 2.57 (m, 2H), 2.48 - 2.35 (m, 2H), 2.03 - 1.96 (m, 1H), 1.73 - 1.66 (m, 4H), 1.63 - 1.48 (m, 6H), 1.26 - 1.24 (m, 1H) 40 905.4 10.97 (s, 1H), 10.85 (s, 1H), 8.36 (t, J = 2.0 Hz, 1H), 8.05 - 7.95 (m, 2H), 7.79(d, J = 8.3 Hz, 2H), 7.76 - 7.61 (m, 5H), 7.51 - 7.42 (m, 2H), 7.42 - 7.34 (m, 2H), 6.71 (s, 1H), 5.11 (dd, J= 13.3, 5.1 Hz, 1H), 4.59 (t, J = 6.1 Hz, 2H), 4.43 (d, J = 17.3 Hz, 1H), 4.29 (d, J = 17.2 Hz, 1H), 3.48 (s, 3H), 3.39 (s, 2H), 3.26 (t, J = 6.1 Hz, 3H), 2.99 - 2.85 (m, 1H), 2.64 (d, J = 7.7 Hz, 6H), 2.52 (d, J = 2.0 Hz, 2H), 2.46 - 2.33 (m, 1H), 2.05 - 1.96 (m, 4H), 1.78 - 1.48 (m, 6H), 1.26 - 1.18 (m, 2H)41 906.7 10.94 (s, 1H), 10.83 (s, 1H), 8.37 - 8.36 (m, 1H), 8.04 - 7.97 (m, 2H), 7.80 - 7.77 (m, 2H), 7.68 - 7.62 (m, 4H), 7.50 - 7.44 (m, 2H), 7.40 (s, 1H), 7.01 - 6.98 (m, 2H), 6.71 (s, 1H), 5.03 (dd, J = 8.0, 5.2 Hz, 1H), 4.62 (t, J = 5.6 Hz, 2H), 4.31 (d, J = 16.8 Hz, 1H), 4.19 (d, J = 16.8 Hz, 1H), 3.62 - 3.57 (m, 3H), 3.48 (s, 3H), 3.26 (t, J = 5.6 Hz, 2H), 3.13 (t, J = 6.4 Hz, 2H), 2.97 - 2.78 (m, 3H), 2.63 - 2.60 (m, 3H), 2.60 - 2.51 (m, 1H), 2.50 - 2.27 (m, 3H), 2.04 - 2.03 (m, 1H), 2.03 - 2.02 (m, 2H), 2.00-1.92 (m, 1H), 1.90 - 1.70 (m, 1H), 1.48 - 1.44 (m, 2H), 1.03 - 0.99 (m, 2H)42 920.4 8.46 (s, 1H), 7.95 (d, J = 9.2 Hz, 2H), 7.86 - 7.71 (m, 5H), 7.64 (d, J = 8.7 Hz,1H), 7.59 (t, J = 7.9 Hz, 1H), 7.13 - 6.95 (m, 3H), 5.12 (dd, J = 13.3, 5.1 Hz, 1H), 4.79 (s, 2H), 4.48 - 4.32 (m, 3H), 4.08 (d, J = 26.4 Hz, 3H), 3.93 (d, J = 12.9 Hz, 2H), 3.59 (d, J = 19.6 Hz, 6H), 3.40 (s, 3H), 3.18 - 2.93 (m, 2H), 2.93 - 2.61 (m, 7H), 2.50 - 2.40 (m, 1H), 2.23 - 2.10 (m, 1H), 1.74 (t, J = 24.6 Hz, 3H), 1.34 (s, 2H)43 956.2 12.33 (s, 1H), 10.86 (s, 1H), 10.75 (s, 1H), 8.12 - 8.05 (m, 1H), 7.85 - 7.68 (m, 6H), 7.35 (t, J = 8.0 Hz, 1H), 7.30 (s, 1H), 7.12 (s, 1H), 6.75 (s, 1H), 6.13 (d, J = 11.2 Hz, 2H), 4.83 - 4.78 (m, 2H), 4.02 (dd, J = 12.4, 5.2 Hz, 1H), 3.93 (t, J = 8.0 Hz, 2H), 3.80 - 3.77 (m, 2H), 3.69 - 3.61 (m, 1H), 3.48 (s, 3H), 3.43 (t, J = 5.6 Hz, 2H), 3.23 - 3.15 (m, 2H), 3.13 - 3.08 (m, 1H), 3.07 - 2.91 (m, 2H), 2.87 - 2.71 (m, 2H), 2.64 (s, 3H), 2.52 (s, 3H), 2.14 - 2.01 (m, 1H), 1.98 - 1.85 (m, 1H), 1.53 - 1.29 (m, 2H), 1.13 - 0.90 (m, 2H)44 887.4 10.87 (s, 2H), 8.34 (s, 1H), 8.00 - 7.95 (m, 2H), 7.79 (d, J = 7.6 Hz, 2H), 7.67- 7.62 (m, 4H), 7.46 (t, J = 8.0 Hz, 1H), 7.40 (s, 1H), 6.71 (s, 1H), 6.13 (s, 1H), 6.10 (s, 1H), 4.70 - 4.62 (m, 2H), 4.04 (dd, J = 12.4, 5.2 Hz, 1H), 3.91 - 3.86 (m, 4H), 3.74 - 3.68 (m, 3H), 3.48 (s, 3H), 3.42 - 3.40 (m, 1H), 3.39 - 3.38 (m, 2H), 3.26 - 3.24 (m, 2H), 3.24 - 3.22 (m, 1H), 2.78 - 2.75 (m, 1H),2.68 (s, 3H), 2.67 - 2.50 (m, 4H), 2.09 - 2.05 (m, 1H), 1.96 - 1.94 (m, 1H)WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+45 905.4 10.98 (s, 1H), 10.92 (s, 1H), 8.42 - 8.38 (m, 1H), 8.35 - 8.27 (m, 2H), 8.05 - 7.94 (m, 2H), 7.84 - 7.78 (m, 3H), 7.72 - 7.67 (m, 2H), 7.66 - 7.61 (m, 2H), 7.50 - 7.44 (m, 2H), 7.41 - 7.34 (m, 2H), 6.82 (s, 1H), 5.10 (dd, J = 13.2, 5.2 Hz, 1H), 4.72 - 4.62 (m, 2H), 4.41 (d, J = 17.2 Hz, 1H), 4.28 (d, J = 17.2 Hz, 1H), 3.49 (s, 3H), 3.27 - 3.19 (m, 3H), 2.98 - 2.84 (m, 1H), 2.77 - 2.68 (m, 2H), 2.64 - 2.55 (m, 2H), 2.51 (s, 3H), 2.41 - 2.34 (m, 1H), 2.10 - 1.93 (m, 5H), 1.88 - 1.86 (m, 2H), 1.73 - 1.49 (m, 6H), 1.04 - 0.94 (m, 2H)46 886.4 10.96 (s, 1H), 10.86 (s, 1H), 8.36 (s, 1H), 8.05 - 7.96 (m, 2H), 7.79 (d, J = 8.4Hz, 2H), 7.72 - 7.61 (m, 4H), 7.47 (t, J = 8.0 Hz, 1H), 7.39 (s, 1H), 7.00 (d, J = 9.6 Hz, 2H), 6.71 (s, 1H), 4.59 (s, 2H), 4.20 (dd, J = 12.4, 5.2 Hz, 1H), 3.48 (s, 3H), 3.26 (t, J = 6.4 Hz, 3H), 2.88 - 2.75 (m, 1H), 2.70 - 2.59 (m, 5H), 2.55 (d, J = 3.6 Hz, 1H), 2.51 -2.48 (m, 3H), 2.44 (d, J = 12.4 Hz, 1H), 2.16 - 2.09 (m, 1H), 2.04 - 1.98 (m, 4H), 1.69 - 1.60 (m, 4H), 1.58 - 1.48 (m, 2H), 1.25 - 1.20 (m, 2H)47 858.4 10.95 (s, 1H), 10.83 (s, 1H), 8.34 (s, 1H), 8.06 - 7.91 (m, 2H), 7.78 (d, J = 8.0Hz, 2H), 7.73 - 7.56 (m, 4H), 7.46 (t, J = 8.0 Hz, 1H), 7.38 (s, 1H), 7.03 (d, J = 10.4 Hz, 2H), 6.70 (s, 1H), 4.62 - 4.60 (m, 2H), 4.20 (dd, J = 12.4, 4.8 Hz, 1H), 3.60 (t, J = 6.4 Hz, 1H), 3.48 (s, 3H), 3.44 - 3.41 (m, 1H), 3.30 - 3.29 (m, 1H), 3.23 (t, J = 5.6 Hz, 3H), 2.86 - 2.83 (m, 3H), 2.67 - 2.63 (m, 5H), 2.55 (s, 3H), 2.16 - 2.09 (m, 2H), 2.01 - 1.99 (m, 1H), 1.62 - 1.60 (m, 2H), 1.40 - 1.38 (m, 2H)48 858.4 10.96 (s, 1H), 10.84 (s, 1H), 8.35 (s, 1H), 8.01 - 7.96 (m, 2H), 7.78 (d, J = 8.0Hz, 2H), 7.67 (d, J = 8.0 Hz, 2H), 7.62 (d, J = 8.0 Hz, 1H), 7.57 (s, 1H), 7.45 (t, J = 8.0 Hz, 1H), 7.38 (s, 1H), 7.04 (d, J = 10.4 Hz, 2H), 6.69 (s, 1H), 4.62 - 4.60 (m, 2H), 4.24 - 4.20 (m, 1H), 3.48 (s, 3H), 3.33 - 3.20 (m, 5H), 2.85 - 2.82 (m, 3H), 2.61 (s, 3H), 2.60 - 2.56 (m, 1H), 2.51 - 2.50 (m, 1H), 2.44 - 2.42 (m, 1H), 2.32 - 2.30 (m, 1H), 2.14 - 2.12 (m, 1H), 2.03 - 2.01 (m, 1H), 1.90 - 1.88 (m, 2H), 1.23 - 1.20 (m, 3H)49 901.5 10.85 (s, 2H), 8.34 (t, J = 2.0 Hz, 1H), 8.01 - 7.90 (m, 2H), 7.80 - 7.77 (m,2H), 7.70 - 7.64 (m, 2H), 7.63 - 7.62 (m, 2H), 7.46 (t, J = 8.0 Hz, 1H), 7.39 (s, 1H), 6.71 (s, 1H), 6.09 - 6.08 (m, 1H), 6.05 - 6.04 (m, 1H), 4.61 (t, J = 5.6 Hz, 2H), 4.02 (dd, J = 12.4, 4.8 Hz, 1H), 3.87 - 3.83 (m, 2H), 3.48 (s, 3H), 3.39 - 3.35 (m, 4H), 2.84 - 2.73 (m, 3H), 2.63 (s, 3H), 2.55 - 2.54 (m, 1H), 2.51 (s, 3H), 2.35 - 2.33 (m, 2H), 2.30 - 2.20 (m, 2H), 2.10 - 2.00 (m, 1H), 1.98 - 1.89 (m, 1H), 1.79 - 1.74 (m, 2H), 1.40 - 1.30 (m, 2H), 1.05 - 0.95 (m, 2H) 50 921.7 11.06 (s, 1H), 10.83 (s, 1H), 8.36 (s, 1H), 8.28 (s, 1H), 8.04 (d, J = 8.4 Hz,1H), 7.98 (s, 1H), 7.80 (d, J = 8.4 Hz, 2H), 7.69 - 7.64 (m, 4H), 7.47 (t, J = 8.0 Hz, 1H), 7.39 (s, 1H), 6.92 (d, J = 8.4 Hz, 1H), 6.78 (d, J = 2.0 Hz, 1H), 6.72 (s, 1H), 6.59 (dd, J = 8.4, 2.0 Hz, 1H), 5.31 - 5.26 (m, 1H), 4.63 (s, 2H), 3.59 (t, J = 6.0 Hz, 1H), 3.48 (s, 3H), 3.27 - 3.25 (m, 8H), 3.12 (t, J = 7.6 Hz, 2H), 2.89 - 2.85 (m, 1H), 2.67 - 2.58 (m, 7H), 2.25 (d, J = 7.6 Hz, 2H), 2.00 - 1.97 (m, 1H), 1.70 - 1.68 (m, 1H), 1.49 - 1.47 (m, 2H), 1.10 - 1.07 (m, 2H) 51 901.7 10.85 (s, 2H), 8.34 (t, J = 2.0 Hz, 1H), 8.01 - 7.90 (m, 2H), 7.80 - 7.77 (m,2H), 7.71 - 7.64 (m, 2H), 7.63 - 7.62 (m, 2H), 7.46 (t, J = 8.0 Hz, 1H), 7.39 (s, 1H), 6.71 (s, 1H), 6.09 - 6.06 (m, 2H), 4.61 (t, J = 5.2 Hz, 2H), 4.02 (dd, J = 12.4, 5.2 Hz, 1H), 3.87 - 3.83 (m, 2H), 3.48 (s, 3H), 3.39 - -3.32 (m, 4H), 2.83 - 2.67 (m, 3H), 2.63 (s, 3H), 2.55 - 2.54 (m, 1H), 2.51 (s, 3H), 2.33 (d, J = 6.8 Hz, 2H), 2.30 - 2.20 (m, 2H), 2.10 - 2.00 (m, 1H), 1.98 - 1.89 (m, 1H), 1.78 - 1.73 (m, 2H), 1.40 - 1.30 (m, 2H), 1.04 - 1.01 (m, 2H)53 892.5 11.30 (s, 1H), 11.00 (s, 1H), 8.44 (d, J = 9.2 Hz, 1H), 7.80 (d, J = 8.4 Hz, 2H),7.74 - 7.65 (m, 5H), 7.46 (s, 1H), 7.38 (d, J = 8.0 Hz, 1H), 6.76 (s, 1H), 6.53 (s, 1H), 5.11 (dd, J= 13.2, 5.2 Hz, 1H), 4.81 - 4.65 (m, 2H), 4.45 (d, J = 17.2 Hz, 1H), 4.32 (d, J = 17.2 Hz, 1H), 3.50 (s, 3H), 3.45 - 3.40 (m, 1H), 3.28 -3.18 (m, 3H), 3.09 - 2.80 (m, 5H), 2.70 - 2.62 (m, 7H), 2.43 - 2.36 (m, 1H),WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+2.17 - 1.70 (m, 9H), 1.70- 1.54 (m, 1H), 1.25 - 1.11 (m, 2H), 0.62 - 0.09 (m, 3H)54 886.6 10.95 (s, 1H), 10.82 (s, 1H), 8.35 - 8.32 (m, 2H), 8.04 (d, J = 8.0 Hz, 1H), 7.97(s, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.70 - 7.61 (m, 4H), 7.47 (t, J = 8.0 Hz, 1H), 7.39 (s, 1H), 7.00 (d, J = 10.4 Hz, 2H), 6.71 (s, 1H), 4.64 - 4.62 (m, 2H), 4.20 (dd, J = 12.4, 5.2 Hz, 1H), 3.48 (s, 3H), 3.24 (t, J = 5.6 Hz, 3H), 2.88 - 2.75 (m, 1H), 2.69 - 2.66 (m, 2H), 2.64 (s, 3H), 2.49 - 2.43 (m, 4H), 2.38 - 2.32 (m, 4H), 2.14 - 2.07 (m, 1H), 2.03 - 1.96 (m, 4H), 1.56 - 1.46 (m, 6H) 55 886.6 10.95 (s, 1H), 10.82 (s, 1H), 8.36 (t, J = 2.0 Hz, 1H), 8.26 (s, 1H), 8.03 - 8.00(m, 1H), 7.98 (s, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.70 - 7.61 (m, 4H), 7.47 (t, J = 8.0 Hz, 1H), 7.39 (s, 1H), 7.00 (d, J = 10.4 Hz, 2H), 6.71 (s, 1H), 4.60 - 4.57 (m, 2H), 4.20 (dd, J = 12.4, 5.2 Hz, 1H), 3.48 (s, 3H), 3.27 - 3.24 (m, 3H), 2.88 - 2.75 (m, 1H), 2.66 - 2.61 (m, 5H), 2.55 - 2.40 (m, 5H), 2.18 - 2.09 (m, 1H), 2.03 - 1.96 (m, 4H), 1.68 - 1.46 (m, 6H), 1.24 - 1.17 (m, 2H)57 949.5 10.88 (s, 1H), 10.84 (s, 1H), 10.81 (s, 1H), 8.47 (t, J = 2.0 Hz, 1H), 8.07 (d, J =8.0 Hz, 1H), 7.83 - 7.78 (m, 3H), 7.68 (d, J = 8.4 Hz, 2H), 7.64 (s, 1H), 7.60 (d, J = 2.0 Hz, 1H), 7.52 (t, J = 8.0 Hz, 1H), 7.00 (d, J = 13.6 Hz, 1H), 6.92 - 6.88 (m, 2H), 6.73 (s, 1H), 6.61 (d, J = 2.0 Hz, 1H), 4.67 - 4.64 (m, 2H), 3.79 - 3.78 (m, 1H), 3.77 (s, 3H), 3.48 (s, 3H), 3.33 - 3.30 (m, 4H), 3.22 - 3.18 (m, 2H), 2.69 - 2.61 (m, 5H), 2.62 - 2.60 (m, 2H), 2.50 - 2.47(m, 3H), 2.23 - 2.12 (m, 1H), 2.04 - 1.96 (m, 1H), 1.63 - 1.53 (m, 3H), 1.26 - 1.13 (m, 4H), 0.86- 0.81 (m, 1H)58 929.4 10.88 (s, 1H), 10.85 (s, 1H), 8.45 (q, J = 4.4 Hz, 1H), 8.33 (t, J = 2.0 Hz, 1H),7.99 - 7.97 (m, 1H), 7.77 (d, J = 8.0 Hz, 2H), 7.69 (d, J = 8.0 Hz, 2H), 7.64 (s, 1H), 7.59 - 7.55 (m, 1H), 7.47 (t, J = 8.0 Hz, 1H), 6.71 (s, 1H), 6.13 (d, J = 11.2 Hz, 2H), 4.69 - 4.58 (m, 2H), 4.02 (dd, J = 12.4, 4.8 Hz, 1H), 3.96 (t, J = 8.0 Hz, 2H), 3.81-3.79 (m, 2H), 3.70 - 3.60 (m, 1H), 3.47 (s, 3H), 3.39 (t, J = 5.6 Hz, 2H), 3.25 - 3.21 (m, 1H), 3.14- 3.05 (m, 1H), 3.08 - 2.92 (m, 2H), 2.80 (d, J = 4.4 Hz, 3H), 2.79 - 2.74 (m, 2H), 2.66 (s, 3H), 2.62 - 2.50 (m, 1H), 2.50 (s, 3H), 2.12- 2.01 (m, 1H), 1.99 - 1.89 (m, 1H), 1.43 - 1.28 (m, 2H), 1.10 - 0.91 (m, 2H)59 933.6 10.92 (s, 1H), 10.85 (s, 1H), 8.19 (dd, J = 6.4, 2.4 Hz, 1H), 7.99 - 7.95 (m,1H), 7.77 (d, J = 8.0 Hz, 2H), 7.76 - 7.66 (m, 4H), 7.62 (s, 1H), 7.31 (t, J = 9.6 Hz, 1H), 6.70 (s, 1H), 6.15 (d, J = 11.2 Hz, 2H), 4.65 - 4.60 (m, 2H), 4.08 - 3.97 (m, 1H), 3.95 (t, J = 8.4 Hz, 2H), 3.85 - 3.79 (m, 2H), 3.77 - 3.67 (m, 1H), 3.47 (s, 3H), 3.38 (t, J = 5.6 Hz, 2H), 3.27 - 3.24 (m, 1H), 3.11 - 3.08 (m, 1H), 3.04 - 2.95 (m, 2H), 2.81 - 2.74 (m, 3H), 2.62 (s, 3H), 2.49 (s, 3H), 2.12 - 2.01 (m, 1H), 1.98 - 1.90 (m, 1H), 1.43 - 1.29 (m, 2H), 1.10 - 0.94 (m, 2H) 60 860.3 11.33 (s, 1H), 10.87 (s, 1H), 8.41 (d, J = 9.2 Hz, 1H), 7.80 (d, J = 8.0 Hz, 2H),7.71 - 7.66 (m, 4H), 6.76 (s, 1H), 6.15 (d, J = 10.4 Hz, 2H), 4.79 - 4.73 (m, 2H), 4.04 (dd, J = 12.8, 5.2 Hz, 1H), 3.93 - 3.86 (m, 4H), 3.75 - 3.66 (m, 3H), 3.49 (s, 3H), 3.42 - 3.32 (m, 3H), 3.30 - 3.25 (m, 1H), 3.20 (dd, J = 10.4, 3.2 Hz, 1H), 2.82 - 2.73 (m, 1H), 2.65 (s, 3H), 2.61 (s, 3H), 2.50 - 2.49 (m, 4H), 2.11 - 2.06 (m, 1H), 1.97 - 1.93 (m, 1H)61 905.3 10.86 (s, 1H), 10.70 (s, 1H), 8.19 (s, 1H), 8.18 - 8.12 (m, 1H), 7.84 - 7.76 (m,3H), 7.72 - 7.63 (m, 4H), 7.49 - 7.40 (m, 1H), 7.31 (t, J = 9.6 Hz, 1H), 6.74 (s, 1H), 6.12 (d, J = 11.2 Hz, 2H), 4.82 – 4.77 (m, 2H), 4.03 (dd, J = 12.8, 5.2 Hz, 1H), 3.97 - 3.84 (m, 4H), 3.79 - 3.64 (m, 3H), 3.48 (s, 3H), 3.41 - 3.37 (m, 1H), 3.38 - 3.33 (m, 4H), 3.25 - 3.17 (m, 1H), 2.84 - 2.71 (m, 1H), 2.64 (s, 3H), 2.52 (s, 3H), 2.14- 2.00 (m, 1H), 1.98 - 1.92 (m, 1H)62 905.2 10.91 (s, 1H), 10.86 (s, 1H), 8.18 (dd, J = 6.4, 2.8 Hz, 1H), 7.99 - 7.91 (m,1H), 7.81 - 7.77 (m, 2H), 7.72 - 7.70 (m, 2H), 7.68 - 7.64 (m, 3H), 7.31 (t, J = 9.6 Hz, 1H), 6.71 (s, 1H), 6.11 (d, J = 11.2 Hz, 2H), 4.67 - 4.62 (m, 2H), 4.03(dd, J = 12.4, 5.2 Hz, 1H), 3.95 - 3.82 (m, 4H), 3.77 - 3.66 (m, 3H), 3.48 (s,WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+3H), 3.44 - 3.38 (m, 2H), 3.38 - 3.28 (m, 3H), 3.27 - 3.19 (m, 1H), 2.83 - 2.71 (m, 1H), 2.63 (s, 3H), 2.51 (s, 3H), 2.11 - 2.04 (m, 1H), 1.97- 1.92 (m, 1H)63 995.3 10.91 (s, 1H), 10.86 (s, 1H), 10.83(s, 1H), 8.44 (t, J = 1.6 Hz, 1H), 8.04 (dd, J = 8.4, 1.6 Hz, 1H), 7.80 - 7.77 (m, 3H), 7.68 (d, J = 8.4 Hz, 2H), 7.64 (s, 1H), 7.59 (d, J = 2.4 Hz, 1H), 7.51 (t, J = 7.6 Hz, 1H), 6.72 (s, 1H), 6.60 (d, J = 2.0 Hz, 1H), 6.12 (d, J = 11.2 Hz, 2H), 4.67 - 4.60 (m, 2H), 4.03 (dd, J = 12.8, 5.2 Hz, 1H), 3.96- 3.91 (m, 2H), 3.83 - 3.79 (m, 2H), 3.78 (s, 3H), 3.68 - 3.52 (m, 1H), 3.48 (s, 3H), 3.44 - 3.39 (m, 1H), 3.34 - 3.29 (m, 2H), 3.11 - 3.09 (m, 1H), 3.09 - 2.92 (m, 2H), 2.81 - 2.74 (m, 2H), 2.64 (s, 3H), 2.48 (s, 3H), 2.48 - 2.46 (m, 1H), 2.14 - 2.01 (m, 1H), 1.99- 1.90 (m, 1H), 1.50 - 1.30 (m, 2H), 1.10 - 0.90 (m, 2H)64 888.3 11.32 (s, 1H), 10.88 (s, 1H), 8.40 (d, J = 9.2 Hz, 1H), 7.79 (d, J = 8.4 Hz, 2H),7.74 - 7.62 (m, 4H), 6.75 (s, 1H), 6.64 - 6.60 (m, 2H), 4.78 (t, J = 5.4 Hz, 2H), 4.14 - 3.94 (m, 2H), 3.87 - 3.83 (m, 1H), 3.78 - 3.64 (m, 4H), 3.49 (s, 3H), 3.19 - 3.16 (m, 2H), 2.81 - 2.70 (m, 4H), 2.65 (s, 3H), 2.62 (s, 3H), 2.53 (s, 3H), 2.20 - 1.95 (m, 3H), 1.53 - 1.39 (m, 4H)65 922.4 10.89 (s, 1H), 10.87 (s, 1H), 8.20 (dd, J = 6.4, 2.8 Hz, 2H), 8.03 - 7.99 (m,1H), 7.82 - 7.79 (m, 2H), 7.72 - 7.67 (m, 4H), 7.63 (s, 1H), 7.60 (d, J = 8.4 Hz, 1H), 7.40 (s, 1H), 7.32 (t, J = 9.2 Hz, 1H), 7.00 (dd, J = 8.4, 1.2 Hz, 1H), 6.71 (s, 1H), 4.63 (t, J = 5.6 Hz, 2H), 4.32 (dd, J = 9.6, 5.2 Hz, 1H), 3.96 (s, 3H), 3.55 - 3.52 (m, 1H), 3.47 (s, 3H), 3.24 (t, J = 5.6 Hz, 2H), 2.81 - 2.77 (m, 2H), 2.71 -2.55 (m, 6H), 2.53 - 2.51 (m, 4H), 2.39 - 2.29 (m, 1H), 2.19 - 2.11 (m, 1H), 1.76- 1.53 (m, 10H)66 941.4 10.90 (s, 1H), 10.55 (s, 1H), 8.22 - 8.18 (m, 1H), 8.03 - 7.99 (m, 1H), 7.83 - 7.77 (m, 2H), 7.74 - 7.66 (m, 4H), 7.64 (s, 1H), 7.56 (d, J = 6.0 Hz, 1H), 7.39 - 7.28 (m, 2H), 6.72 (s, 1H), 4.63 (t, J = 5.6 Hz, 2H), 3.98 (s, 3H), 3.90 (t, J = 6.8 Hz, 2H), 3.56 - 3.50 (m, 1H), 3.48 (s, 3H), 3.33 (m, 3H), 3.24 (t, J = 5.6 Hz, 2H), 2.79 - 2.71 (m, 5H), 2.64 (s, 3H), 2.47 - 2.37 (m, 1H), 1.72 - 1.64 (m, 8H), 1.58 - 1.49 (m, 2H)67 904.4 10.88 (s, 1H), 10.83 (s, 1H), 8.34 (t, J = 2.0 Hz, 1H), 8.05 - 8.03 (m, 1H), 7.97(s, 1H), 7.80 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.66-7.62 (m, 2H), 7.59 (d, J = 8.4 Hz, 1H), 7.47 (t, J = 8.0 Hz, 1H), 7.41 (s, 1H), 7.39 (s, 1H), 7.01 (dd, J = 8.8, 1.6 Hz, 1H), 6.72 (s, 1H), 4.66 (t, J = 5.6 Hz, 2H), 4.32 (dd, J = 9.6, 5.2 Hz, 1H), 3.96 (s, 3H), 3.55 - 3.52 (m, 1H), 3.48 (s, 3H), 3.25 (t, J = 5.6 Hz, 3H), 2.76 - 2.56 (m, 10H), 2.40 - 2.34 (m, 2H), 2.20 - 2.14 (m, 1H), 1.73 - 1.51 (m, 11H)68 923.4 10.84 (s, 1H), 10.55 (s, 1H), 8.35 (t, J = 2.0 Hz, 1H), 8.03 (dd, J = 8.0, 2.0 Hz,1H), 7.97 (s, 1H), 7.80 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.65 - 7.63 (m, 2H), 7.56 (d, J = 6.0 Hz, 1H), 7.47 (t, J = 8.0 Hz, 1H), 7.38 (s, 1H), 7.36 (d, J = 10.8 Hz, 1H), 6.72 (s, 1H), 4.64 (d, J = 5.6 Hz, 2H), 3.98 (s, 3H), 3.90 (t, J = 6.8 Hz, 2H), 3.55 - 3.52 (m, 1H), 3.48 (s, 3H), 3.25 (t, J = 5.6 Hz, 2H), 2.79 - 2.72 (m, 5H), 2.64 (s, 3H), 2.54 (s, 3H), 2.44 - 2.38 (m, 1H), 1.70 - 1.51 (m, 10H)69 894.3 11.27 (s, 1H), 11.06 (s, 1H), 8.46 (d, J = 9.2 Hz, 1H), 8.19 (s, 1H), 8.02 (d, J =8.4 Hz, 2H), 7.70 - 7.67 (m, 4H), 6.92 (d, J = 8.4 Hz, 1H), 6.80 (d, J = 2.0 Hz, 1H), 6.77 (s, 1H), 6.60 (dd, J = 8.0, 2.0 Hz, 1H), 6.54 (s, 1H), 5.28 (dd, J = 12.8, 5.6 Hz, 1H), 4.76 - 4.73 (m, 2H), 3.59 (t, J = 6.0 Hz, 2H), 3.48 (s, 3H), 3.30 (s, 3H), 3.24 - 3.22 (m, 2H), 3.13 - 3.11 (m, 2H), 2.93 - 2.86 (m, 1H), 2.68 - 2.54 (m, 13H), 2.20 (t, J = 6.4 Hz, 2H), 2.00 - 1.97 (m, 1H), 1.66 - 1.60 (m, 1H), 1.51 - 1.46 (m, 2H), 1.13 - 1.06 (m, 2H)70 922.5 10.92 (s, 1H), 10.88 (s, 1H), 8.26 - 8.18 (m, 1H), 8.02 - 7.96 (m, 1H), 7.79 (d,J = 8.4 Hz, 2H), 7.72 - 7.66 (m, 4H), 7.63 (s, 1H), 7.60 (d, J = 8.0 Hz, 1H),7.41 (s, 1H), 7.37 - 7.28 (m, 1H), 7.01 (d, J = 8.0 Hz, 1H), 6.71 (s, 1H), 4.59WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+(t, J = 6.2 Hz, 2H), 4.36 - 4.28 (m, 1H), 3.97 (s, 3H), 3.48 (s, 3H), 3.31 - 3.22 (m, 3H), 2.73 - 2.65 (m, 3H), 2.65 - 2.63 (m, 4H), 2.62 - 2.54 (m, 1H), 2.51 (s, 3H), 2.40 - 2.28 (m, 1H), 2.22 - 2.10 (m, 1H), 2.06 - 2.01 (m, 2H), 1.77 - 1.56 (m, 6H), 1.30- 1.16 (m, 2H)71 941.7 10.91 (s, 1H), 10.55 (s, 1H), 8.25 - 8.18 (m, 1H), 8.01 - 7.95 (m, 1H), 7.79 (d,J = 8.0 Hz, 2H), 7.73 - 7.65 (m, 4H), 7.63 (s, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.39 - 7.28 (m, 2H), 6.71 (s, 1H), 4.62-4.54 (m, 2H), 4.00 (s, 3H), 3.91 (t, J = 6.8 Hz, 2H), 3.48 (s, 3H), 3.29 - 3.22 (m, 4H), 2.75 (t, J = 6.8 Hz, 3H), 2.70 - 2.68 (m, 2H), 2.63 (s, 3H), 2.51 (s, 3H), 2.05 - 1.99 (m, 2H), 1.76 - 1.63 (m, 5H), 1.29 - 1.16 (m, 3H)72 904.5 10.87 - 10.85 (m, 2H), 8.36 (t, J = 2.0 Hz, 1H), 8.04 - 7.99 (m, 1H), 7.97 (s,1H), 7.83 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.64 (d, J = 6.6 Hz, 2H), 7.60 (d, J = 8.4 Hz, 1H), 7.47 (t, J = 8.0 Hz, 1H), 7.42 (s, 1H), 7.39 (s, 1H), 7.01 (dd, J = 8.8, 1.6 Hz, 1H), 6.71 (s, 1H), 4.60 (t, J = 5.6 Hz, 2H), 4.33 (dd, J = 9.6, 5.2 Hz, 1H), 3.97 (s, 3H), 3.48 (s, 3H), 3.32 - 3.30 (m, 3H), 3.28 - 3.25 (m, 2H), 2.65 - 2.62 (m, 5H), 2.58 - 2.52 (m, 3H), 2.34 - 2.33 (m, 1H), 2.14 - 2.12 (m, 1H), 2.04 - 2.02 (m, 3H), 1.69- 1.66 (m, 6H), 1.35 - 1.16 (m, 3H)73 922.4 10.87 (s, 1H), 10.65 (s, 1H), 8.27 - 8.24 (m, 1H), 7.83 - 7.80 (m, 3H), 7.71 - 7.66 (m, 4H), 7.59 (d, J = 8.0 Hz, 1H), 7.48 - 7.44 (m, 1H), 7.41 (s, 1H), 7.33 (t, J = 8.0 Hz, 1H), 7.02 - 6.99 (m, 1H), 6.76 (s, 1H), 4.81 - 4.79 (m, 2H), 4.34 -4.31 (m, 1H), 3.96 (s, 3H), 3.54 - 3.51 (m, 1H), 3.48 (s, 3H), 3.25 - 3.22 (m, 2H), 2.75 - 2.72 (m, 2H), 2.66 (s, 3H), 2.64 - 2.55 (m, 2H), 2.51 (s, 3H), 2.39 - 2.30 (m, 2H), 2.20 - 2.13 (m, 1H), 1.75 - 1.68 (m, 4H), 1.65 - 1.56 (m, 4H), 1.50 - 1.42 (m, 3H)74 918.8 10.88 (s, 1H), 10.85 (s, 1H), 8.45 (q, J = 4.8 Hz, 1H), 8.32 (t, J = 2.0 Hz, 1H),8.03 (dd, J = 8.0, 2.0 Hz, 1H), 7.83 - 7.77 (m, 2H), 7.72 - 7.66 (m, 2H), 7.64 (s, 1H), 7.63 - 7.55 (m, 2H), 7.48 (t, J = 8.0 Hz, 1H), 7.41 (s, 1H), 7.01 (dd, J = 8.4, 1.6 Hz, 1H), 6.72 (s, 1H), 4.66 (t, J = 6.0 Hz, 2H), 4.33 (dd, J = 9.6, 5.2 Hz, 1H), 3.97 (s, 3H), 3.56 - 3.53 (m, 1H), 3.48 (s, 3H), 3.25 (t, J = 6.0 Hz, 2H), 2.79 - 2.67 (m, 5H), 2.64 - 2.67 (m, 5H), 2.51 (s, 4H), 2.44 - 2.28 (m, 2H), 2.19 -2.13 (m, 1H), 1.87- 1.47 (m, 10H)75 877.5 11.28 (s, 1H), 10.88 (s, 1H), 8.43 (d, J = 8.8 Hz, 1H), 8.30 (s, 1H, formic),7.80 (d, J = 8.4 Hz, 2H), 7.72 - 7.65 (m, 4H), 7.61 (d, J = 8.4 Hz, 1H), 7.42 (s, 1H), 7.02 (d, J = 8.4 Hz, 1H), 6.76 (s, 1H), 4.71 (t, J = 5.2 Hz, 2H), 4.36 - 4.30 (m, 1H), 3.97 (s, 3H), 3.48 (s, 3H), 3.30 - 3.20 (m, 3H), 2.70 - 2.57 (m, 4H), 2.64 (s, 3H), 2.61 (s, 3H), 2.54 - 2.51 (m, 1H), 2.49 (s, 3H), 2.41 - 2.28 (m, 1H), 2.22 -2.13 (m, 1H), 2.06- 1.96 (m, 3H), 1.74 - 1.56 (m, 6H), 1.25 - 1.08 (m, 2H)76 877.8 11.20 (s, 1H), 10.88 (s, 1H), 8.46 (d, J = 9.2 Hz, 1H), 7.80 (d, J = 8.4 Hz, 2H),7.73 - 7.65 (m, 4H), 7.59 (d, J = 8.4 Hz, 1H), 7.41 (s, 1H), 7.00 (d, J = 8.4 Hz, 1H), 6.77 (s, 1H), 4.77 (t, J = 5.2 Hz, 2H), 4.35 - 4.28 (m, 1H), 3.96 (s, 3H), 3.54 - 3.48 (m, 1H), 3.48 (s, 3H), 3.21 (t, J = 5.2 Hz, 2H), 2.74 - 2.59 (m, 4H), 2.67 (s, 3H), 2.62 (s, 3H), 2.57 - 2.53 (m, 1H), 2.49 (s, 3H), 2.40 - 2.23 (m, 2H), 2.21 -2.12 (m, 1H), 1.77- 1.62 (m, 5H), 1.61 - 1.52 (m, 3H), 1.50 - 1.42 (m, 1H)77 918.2 10.88 (s, 1H), 10.87 (s, 1H), 8.45 (q, J = 4.8 Hz, 1H), 8.34 (t, J = 2.0 Hz, 1H),8.02 - 7.99 (m, 1H), 7.81 - 7.77 (m, 2H), 7.71 - 7.66 (m, 2H), 7.64 (s, 1H), 7.61 - 7.58 (m, 2H), 7.48 (t, J = 8.0 Hz, 1H), 7.41 (s, 1H), 7.01 (dd, J = 8.4, 1.6 Hz, 1H), 6.72 (s, 1H), 4.59 (t, J = 6.0 Hz, 2H), 4.33 (dd, J = 9.6, 5.2 Hz, 1H), 3.97 (s, 3H), 3.48 (s, 3H), 3.28 - 3.26 (m, 1H), 2.80 (d, J = 4.8 Hz, 3H), 2.68 - 2.57 (m, 8H), 2.51 (s, 3H), 2.39 - 2.30 (m, 1H), 2.19 - 2.13 (m, 1H),2.06 - 1.97 (m, 3H), 1.72- 1.60 (m, 6H), 1.25 - 1.19 (m, 2H)WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+78 922.6 10.88 (s, 1H), 10.66 (s, 1H), 8.22 - 8.17 (m, 1H), 7.83 - 7.80 (m, 3H), 7.71 - 7.66 (m, 4H), 7.59 (d, J = 8.0 Hz, 1H), 7.48 - 7.44 (m, 1H), 7.41 (s, 1H), 7.33 (t, J = 8.0 Hz, 1H), 7.02 - 6.99 (m, 1H), 6.75 (s, 1H), 4.75 - 4.72 (m, 2H), 4.34 - 4.31 (m, 1H), 3.96 (s, 3H), 3.48 (s, 3H), 3.28 - 3.23 (m, 3H), 2.72 - 2.54 (m, 8H), 2.51 (s, 3H), 2.39 - 2.32 (m, 1H), 2.20 - 2.13 (m, 1H), 2.09 - 2.03 (m, 3H), 1.75 - 1.62 (m, 6H), 1.25 - 1.17 (m, 2H)79 923.4 10.84 (s, 1H), 10.55 (s, 1H), 8.40 - 8.36 (m, 2H), 8.02 - 7.97 (m, 2H), 7.80 (d,J = 8.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.65 - 7.63 (m, 2H), 7.56 (d, J = 6.0 Hz, 1H), 7.47 (t, J = 8.0 Hz, 1H), 7.38 (s, 1H), 7.36 (d, J = 10.8 Hz, 1H), 6.72 (s, 1H), 4.61 - 4.58 (m, 2H), 3.98 (s, 3H), 3.90 (t, J = 6.8 Hz, 2H), 3.55 - 3.52 (m, 1H), 3.48 (s, 3H), 3.30 - 3.25 (m, 3H), 2.79 - 2.72 (m, 4H), 2.64 (s, 3H), 2.54 (s, 3H), 2.35 - 2.33 (m, 1H), 2.05 - 1.96 (m, 3H), 1.72 - 1.65 (m, 6H) 80 841.4 11.23 (s, 1H), 10.85 (s, 1H), 8.46 (d, J = 9.2 Hz, 1H), 7.80 (d, J = 8.4 Hz, 2H),7.73 - 7.66 (m, 4H), 7.24 (t, J = 8.0 Hz, 1H), 7.06 - 6.99 (m, 2H), 6.77 (s, 1H), 4.77 (t, J = 5.2 Hz, 2H), 3.86 (dd, J = 12.0, 4.8 Hz, 1H), 3.54 - 3.48 (m, 1H), 3.49 (s, 3H), 3.21 (t, J = 5.2 Hz, 2H), 2.72 - 2.64 (m, 4H), 2.66 (s, 3H), 2.62 (s, 3H), 2.54 - 2.52 (m, 1H), 2.49 (s, 3H), 2.30 - 2.17 (m, 2H), 2.06 - 1.97 (m, 1H), 1.71 - 1.60 (m, 4H), 1.59 - 1.42 (m, 6H)81 913.2 11.94 (s, 1H), 10.87 (s, 1H), 8.36 (d, J = 8.8 Hz, 1H), 8.20 (s, 1H), 7.82 - 7.75(m, 3H), 7.68 - 7.62 (m, 3H), 6.90 (s, 1H), 6.13 (d, J = 11.2 Hz, 2H), 4.62 - 4.45 (m, 2H), 4.04 (dd, J = 12.8, 4.8 Hz, 1H), 3.95 - 3.83 (m, 4H), 3.77 - 3.68 (m, 3H), 3.49 (s, 3H), 3.47 - 3.42 (m, 2H), 3.39 - 3.38 (m, 1H), 3.37 - 3.28 (m, 3H), 2.82 - 2.72 (m, 1H), 2.61 (s, 3H), 2.51 (s, 3H), 2.17 - 2.00 (m, 1H), 1.99 - 1.88 (m, 1H)82 942.7 11.64 (s, 1H), 10.79 (s, 1H), 8.33 - 8.30 (m, 2H), 7.73 (d, J = 7.6 Hz, 2H), 7.62(d, J = 8.4 Hz, 3H), 6.94 (s, 1H), 6.53 (d, J = 12.8 Hz, 2H), 4.76 - 4.62 (m, 2H), 3.99 - 3.92 (m, 3H), 3.80 (s, 1H), 3.65 - 3.57 (m, 4H), 3.41 - 3.38 (m, 3H), 3.29 - 3.14 (m, 2H), 2.71 - 2.66 (m, 3H), 2.63 - 2.55 (m, 3H), 2.43 - 2.26 (m, 3H), 2.12- 1.89 (m, 4H), 1.52 - 1.39 (m, 4H)83 874.3 11.33 (s, 1H), 10.85 (d, J = 4.4 Hz, 1H), 8.41 (dd, J = 9.6, 2.8 Hz, 1H), 7.84 - 7.74 (m, 2H), 7.73 - 7.60 (m, 4H), 6.76 (s, 1H), 6.20 (t, J = 12.4 Hz, 2H), 4.93 - 4.60 (m, 2H), 4.13 - 3.93 (m, 2H), 3.86 - 3.84 (m, 1H), 3.78 - 3.63 (m, 1H), 3.49 - 3.48 (m, 4H), 3.34 - 3.30 (m, 3H), 3.28 - 3.07 (m, 4H), 2.91 - 2.88 (m, 1H), 2.84 - 2.72 (m, 1H), 2.66 - 2.61 (m, 6H), 2.51 - 2.50 (m, 1H), 2.49 (s, 3H), 2.17 - 1.80 (m, 4H)84 874.5 11.33 (s, 1H), 10.84 (d, J = 4.0 Hz, 1H), 8.40 (d, J = 8.4 Hz, 1H), 7.79 (d, J =8.0 Hz, 2H), 7.71 - 7.65 (m, 4H), 6.76 (s, 1H), 6.20 (t, J = 12.4 Hz, 2H), 4.81 - 4.79 (m, 2H), 4.07 - 4.02 (m, 2H), 3.87 - 3.86 (m, 1H), 3.71 - 3.69 (m, 1H), 3.60 - 3.48 (m, 1H), 3.49 (s, 3H), 3.32 - 3.30 (m, 3H), 3.30 - 3.13 (m, 4H), 2.94 - 2.89 (m, 1H), 2.85 - 2.75 (m, 1H), 2.65 (s, 3H), 2.61 (s, 3H), 2.51 - 2.50 (m, 1H), 2.49 - 2.48 (m, 3H), 2.20 - 1.80 (m, 4H)85 874.3 11.32 - 11.30 (m, 1H), 10.87 (s, 1H), 8.44 - 8.37 (m, 1H), 7.82 - 7.56 (m,6H), 6.74 (s, 1H), 6.21 - 6.07 (m, 2H), 4.82 - 4.68 (m, 2H), 4.09 - 3.86 (m, 3H), 3.82 - 3.70 (m, 2H), 3.68 - 3.56 (m, 1H), 3.48 (s, 3H), 3.42 - 3.35 (m, 3H), 3.20 - 3.08 (m, 2H), 3.06 - 2.93 (m, 1H), 2.89 - 2.72 (m, 2H), 2.65 - 2.63 (m, 2H), 2.62 (s, 3H), 2.52 (s, 3H), 2.49 - 2.47 (m, 2H), 2.17 - 2.02 (m, 1H), 1.99 - 1.92 (m, 1H), 1.65 - 1.33 (m, 2H)86 874.6 11.28 (d, J = 19.2 Hz, 1H), 10.86 (s, 1H), 8.40 (d, J = 9.2 Hz, 1H), 7.77 (dd, J = 8.4, 2.0 Hz, 2H), 7.72 - 7.62 (m, 4H), 6.74 (s, 1H), 6.15 (dd, J = 11.2, 5.6 Hz, 2H), 4.81 - 4.68 (m, 2H), 4.04 (dd, J = 12.4, 4.8 Hz, 1H), 4.01 - 3.89 (m, 2H), 3.81 - 3.71 (m, 2H), 3.69 - 3.58 (m, 1H), 3.56 - 3.39 (m, 5H), 3.21 - 3.00 (m, 2H), 2.99 - 2.71 (m, 3H), 2.65 (s, 3H), 2.62 (s, 3H), 2.54 - 2.52 (m, 2H), 2.49 (d, J = 1.6 Hz, 3H), 2.15 - 2.01 (m, 1H), 2.00 - 1.90 (m, 1H), 1.68 -1.46 (m, 1H), 1.43 - 1.33 (m, 1H)WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+87 902.3 δ 11.31 (d, J = 4.0 Hz, 1H), 10.84 (d, J = 2.8 Hz, 1H), 8.42 (d, J = 9.2 Hz, 1H),7.82 - 7.75 (m, 2H), 7.73 - 7.65 (m, 4H), 6.77 (s, 1H), 6.20 (dd, J = 12.4, 8.8 Hz, 2H), 4.76 (d, J = 5.2 Hz, 2H), 4.02 (d, J = 11.6 Hz, 1H), 3.49 (d, J = 2.0 Hz, 3H), 3.40 (s, 3H), 3.38 - 3.35 (m, 2H), 3.27 - 3.23 (m, 5H), 3.11 - 3.07 (m, 2H), 2.98 - 2.95 (m, 1H), 2.78 (t, J = 14.4 Hz, 1H), 2.63 (s, 3H), 2.62 (d, J = 2.8 Hz, 3H), 2.52 (s, 3H), 2.15 - 1.87 (m, 4H), 1.37 (d, J = 40.9 Hz, 2H), 0.97 - 0.94 (m, 2H)88 902.3 δ 11.30 (s, 1H), 10.84 (s, 1H), 8.42 (d, J = 9.2 Hz, 1H), 7.79 (d, J = 8.0 Hz,2H), 7.70 - 7.67 (m, 4H), 6.76 (s, 1H), 6.20 (dd, J = 12.0, 8.8 Hz, 2H), 4.80 - 4.72 (m, 2H), 4.03 - 4.00 (m, 1H), 3.49 (s, 3H), 3.38 - 3.32 (m, 4H), 3.27 - 3.23 (m, 5H), 3.09 - 3.04 (m, 2H), 2.98 - 2.92 (m, 1H), 2.83 - 2.78 (m, 1H), 2.65 (s, 3H), 2.62 (s, 3H), 2.55 - 2.52 (m, 1H), 2.49 (s, 3H), 2.10 - 2.03 (m, 2H), 1.95 - 1.92 (m, 2H), 1.42 - 1.39 (m, 1H), 1.39 - 1.24 (m, 1H), 1.15 - 0.95 (m, 2H)89 900.3 11.03 (s, 1H), 10.44 (s, 1H), 8.36 (d, J = 9.2 Hz, 1H), 7.81 - 7.75 (m, 2H), 7.70- 7.59 (m, 4H), 6.71 (s, 1H), 6.05 (d, J = 11.2 Hz, 2H), 4.76 (t, J = 5.6 Hz, 2H), 4.02 - 3.89 (m, 3H), 3.80 (t, J = 6.8 Hz, 2H), 3.76 - 3.54 (m, 3H), 3.46 (s, 3H), 3.45 - 3.37 (m, 2H), 3.24 (t, J = 5.6 Hz, 2H), 2.79 - 2.67 (m, 1H), 2.66 (s, 3H), 2.62 (s, 3H), 2.56 - 2.50 (m, 2H), 2.49 (s, 3H), 2.15 - 2.06 (m, 3H), 2.02 - 1.95 (m, 1H), 1.61 - 1.52 (m, 2H)90 933.3 10.90 (s, 1H), 10.87 (s, 1H), 8.17 (dd, J = 6.8, 6.4 Hz, 1H), 7.97 - 7.94 (m,1H), 7.78 (d, J = 8.0 Hz, 2H), 7.71 (d, J = 8.8 Hz, 2H), 7.67 - 7.63 (m, 3H), 7.31 (t, J = 9.6 Hz, 1H), 6.71 (s, 1H), 6.61 (d, J = 12.8 Hz, 2H), 4.71 - 4.59 (m, 2H), 4.04 - 3.99 (m, 2H), 3.89 - 3.80 (m, 1H), 3.74 - 3.67 (m, 3H), 3.48 (s, 3H), 3.43 - 3.39 (m, 2H), 3.33 - 3.27 (m, 1H), 3.23 - 3.21 (m, 1H), 2.75 - 2.70 (m, 3H), 2.63 (s, 3H), 2.51 - 2.50 (m, 1H), 2.49 (s, 3H), 2.21 - 1.97 (m, 3H), 1.51 - 1.44 (m, 4H)91 933.3 δ 10.87 (s, 1H), 10.70 (s, 1H), 8.16 (t, J = 6.4 Hz, 1H), 7.82 (s, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.70 - 7.65 (m, 4H), 7.43 (t, J = 6.4 Hz, 1H), 7.31 (t, J = 8.0 Hz, 1H), 6.74 (s, 1H), 6.61 (d, J = 12.8 Hz, 2H), 4.80 (t, J = 5.2 Hz, 2H), 4.07 - 4.02 (m, 2H), 3.90 - 3.80 (m, 1H), 3.80 - 3.69 (m, 3H), 3.49 (s, 3H), 3.38 - 3.34 (m, 3H), 3.20 - 3.18 (m, 1H), 2.80 - 2.67 (m, 3H), 2.64 (s, 3H), 2.53 - 2.51 (m, 1H), 2.49 (s, 3H), 2.30 - 1.90 (m, 3H), 2.50 - 1.35 (m, 4H)92 916.2 11.30 (s, 1H), 10.87 (s, 1H), 8.41 (d, J = 9.2 Hz, 1H), 7.78 (d, J = 8.4 Hz, 2H),7.71 - 7.67 (m, 4H), 6.76 (s, 1H), 6.62 (d, J = 12.4 Hz, 2H), 4.76 (t, J = 5.2 Hz, 2H), 4.04 (dd, J = 12.8, 5.2 Hz, 1H), 3.80 - 3.70 (m, 2H), 3.49 (s, 3H), 3.38 (t, J = 5.2 Hz, 2H), 3.36 - 3.30 (m, 2H), 3.13 - 3.05 (m, 1H), 3.05 - 2.81 (m, 2H), 2.80 - 2.70 (m, 3H), 2.69 - 2.67 (m, 1H), 2.65 (s, 3H), 2.62 (s, 3H), 2.52 - 2.51 (m, 1H), 2.49 (s, 3H), 2.20 -2.02 (m, 1H), 2.00 - 1.90 (m, 1H), 1.60 - 1.50 (m, 4H), 1.45 - 1.20 (m, 2H), 1.10 - 0.85 (m, 2H)93 902.4 11.72 (s, 1H), 10.88 (s, 1H), 8.42 (d, J = 9.2 Hz, 1H), 7.84 (s, 1H), 7.82 - 7.76(m, 2H), 7.76 - 7.71 (m, 1H), 7.68 (dd, J = 8.4, 1.4 Hz, 2H), 6.86 (s, 1H), 6.74 - 6.55 (m, 2H), 4.83 - 4.57 (m, 2H), 4.13 - 4.01 (m, 1H), 3.91 - 3.71 (m, 4H), 3.49 (s, 3H), 3.07 - 3.03 (m, 1H), 3.01 - 2.94 (m, 2H), 2.94 - 2.86 (m, 6H), 2.87 - 2.71 (m, 4H), 2.69 - 2.67 (m, 4H), 2.64 - 2.63 (m, 2H), 2.41 - 2.28 (m, 1H), 2.17 - 2.03 (m, 1H), 2.03 - 1.88 (m, 1H), 1.87 - 1.44 (m, 5H)94 896.4 11.28 (s, 1H), 10.55 (s, 1H), 8.42 (d, J = 9.2 Hz, 1H), 7.79 (d, J = 8.0 Hz, 2H),7.73 - 7.65 (m, 4H), 7.55 (d, J = 5.6 Hz, 1H), 7.36 (d, J = 10.8 Hz, 1H), 6.75 (s, 1H), 4.71 (t, J = 5.6 Hz, 2H), 3.99 (s, 3H), 3.90 (t, J = 6.8 Hz, 2H), 3.47 (s, 3H), 3.28 - 3.23 (m, 3H), 2.75 (t, J = 6.8 Hz, 3H), 2.67 - 2.57 (m, 2H), 2.64 (s, 3H), 2.60 (s, 3H), 2.50 (s, 3H), 2.04 - 1.95 (m, 3H), 1.73 - 1.60 (m, 5H), 1.29 - 1.07 (m, 3H)95 896.3 11.23 (s, 1H), 10.55 (s, 1H), 8.45 (d, J = 9.2 Hz, 1H), 7.80 (d, J = 8.4 Hz, 2H),7.73 - 7.66 (m, 4H), 7.54 (d, J = 6.0 Hz, 1H), 7.35 (d, J = 10.8 Hz, 1H), 6.77WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+(s, 1H), 4.76 (t, J = 5.2 Hz, 2H), 3.97 (s, 3H), 3.89 (t, J = 6.8 Hz, 2H), 3.55 - 3.47 (m, 1H), 3.48 (s, 3H), 3.21 (t, J = 5.2 Hz, 2H), 2.79 - 2.68 (m, 5H), 2.66 (s, 3H), 2.62 (s, 3H), 2.51 (s, 3H), 2.31 - 2.23 (m, 1H), 1.75 - 1.61 (m, 6H), 1.60 - 1.51 (m, 2H), 1.50 - 1.42 (m, 2H)96 928.3 11.35 (s, 1H), 10.85 (s, 1H), 8.40 (d, J = 9.2 Hz, 1H), 7.85 - 7.79 (m, 2H), 7.75- 7.63 (m, 4H), 6.74 (s, 1H), 6.13 (d, J = 11.2 Hz, 2H), 4.60 (s, 2H), 4.07 - 3.93 (m, 3H), 3.86 - 3.82 (m, 2H), 3.74 - 3.53 (m, 4H), 3.48 (s, 3H), 3.27 - 2.98 (m, 2H), 2.97 - 2.70 (m, 3H), 2.64 (s, 3H), 2.62 (s, 3H), 2.51 (s, 3H), 2.10 - 2.02 (m, 1H), 1.97 - 1.91 (m, 1H), 1.86 - 1.75 (m, 2H), 1.58 - 1.44 (m, 3H), 1.26 - 1.21 (m, 1H), 1.18 - 1.01 (m, 3H)97 908.2 11.91 (s, 1H), 10.87 (s, 1H), 8.58 (d, J = 9.2 Hz, 1H), 8.02 (d, J = 9.2 Hz, 1H),7.82 - 7.80 (m, 3H), 7.69 (d, J = 8.0 Hz, 2H), 6.84 (s, 1H), 6.62 (d, J = 12.8 Hz, 2H), 4.73 - 4.70 (m, 2H), 4.04 (dt, J = 14.4, 6.4 Hz, 2H), 3.84 - 3.83 (m, 1H), 3.80 - 3.63 (m, 5H), 3.43 - 3.41 (m, 1H), 3.35 - 3.30 (m, 7H), 3.20 - 3.18 (m, 1H), 2.85 - 2.70 (m, 6H), 2.68 - 2.66 (m, 1H), 2.26 - 2.02 (m, 1H), 2.02 - 1.90 (m, 1H), 1.52 - 1.48(m, 4H)98 887.2 12.08 (s, 1H), 10.95 (s, 1H), 8.44 (d, J = 9.2 Hz, 1H), 7.91 (s, 1H), 7.84 - 7.54(m, 5H), 7.12 - 7.02 (m, 2H), 6.95 (s, 1H), 4.60 (t, J = 5.6 Hz, 2H), 4.43 (d, J = 12.8 Hz, 1H), 4.20 (dd, J = 12.8, 5.2 Hz, 1H), 3.67 - 3.64 (m, 2H), 3.48 - 3.46 (m, 3H), 3.44 (d, J = 7.2 Hz, 1H), 3.31 (t, J = 5.6 Hz, 2H), 3.00 - 2.52 (m, 14H), 2.21 - 1.95 (m, 4H), 1.79 - 1.69 (m, 2H), 1.67 - 1.53 (m, 2H), 1.50 - 1.31 (m, 2H)99 905.3 10.88 (s, 1H), 10.65 (s, 1H), 8.34 (dd, J = 10.0, 8.0 Hz, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.72 - 7.59 (m, 3H), 7.28 (d, J = 8.0 Hz, 1H), 6.73 (s, 1H), 6.67 - 6.52 (m, 2H), 4.76 (t, J = 5.6 Hz, 2H), 4.13 - 3.99 (m, 2H), 3.91 - 3.81 (m, 1H), 3.81 - 3.65 (m, 3H), 3.49 (s, 3H), 3.39 - 3.36 (m, 3H), 3.20 - 3.17 (m, 1H), 2.87 - 2.67 (m, 3H), 2.64 (s, 3H), 2.52 - 2.50 (m, 1H), 2.50 - 2.49 (m, 3H), 2.44 (s, 3H), 2.21 - 2.19 (m, 1H), 2.15 - 2.02 (m, 1H), 2.02 - 1.88 (m, 1H), 1.47 - 1.43 (m, 4H)100 947.2 10.92 (s, 1H), 10.86 (s, 1H), 8.28 (q, J = 4.4 Hz, 1H), 8.17 (dd, J = 6.4, 2.8 Hz,1H), 8.05 - 7.90 (m, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H), 7.63 (s, 1H), 7.33 (t, J = 9.6 Hz, 1H), 6.71 (s, 1H), 6.14 (d, J = 11.2 Hz, 2H), 4.62 (t, J = 5.2 Hz, 2H), 4.03 - 4.00 (m, 1H), 3.95 (t, J =8.0 Hz, 2H), 3.82 (t, J = 6.4 Hz, 2H), 3.71 - 3.65 (m, 1H), 3.48 (s, 3H), 3.39 - 3.34 (m, 2H), 3.26 (s, 1H), 3.10 - 3.07 (m, 1H), 2.99 - 2.97 (m, 2H), 2.90 - 2.83 (m, 2H), 2.80 (d, J = 4.4 Hz, 3H), 2.69 - 2.55 (m, 1H), 2.63 (s, 3H), 2.49 (s, 3H), 2.14 - 2.01 (m, 1H), 1.99 - 1.90 (m, 1H), 1.51 - 1.20 (m, 2H), 1.09 - 0.94 (m, 2H)101 987.3 11.00 (s, 1H), 10.80 (s, 1H), 8.28 (s, 1H), 8.06 - 8.04 (m, 1H), 7.90 - 7.86 (m,1H), 7.73 (d, J = 8.4 Hz, 2H), 7.67 - 7.61 (m, 4H), 7.26 (t, J = 9.4 Hz, 1H), 6.92 (s, 1H), 6.53 (d, J = 12.8 Hz, 2H), 4.62 - 4.54 (m, 2H), 3.99 - 3.93 (m, 2H), 3.83 - 3.79 (m, 1H), 3.67 - 3.60 (m, 3H), 3.41 (s, 3H), 3.28 - 3.28 (m, 2H), 3.19 - 3.16 (m, 1H), 2.71 - 2.61 (m, 3H), 2.43 - 2.42 (m, 5H), 2.18 - 2.14 (m, 1H), 2.04 - 2.00 (m, 1H), 1.91 - 1.90 (m, 1H), 1.44 - 1.38 (m, 4H) 102 987.3 10.88 (s, 1H), 10.71 (s, 1H), 8.30 (s, 1H), 7.99 (t, J = 7.2 Hz, 1H), 7.77 - 7.73(m, 3H), 7.64 - 7.62 (m, 3H), 7.44 - 7.41 (m, 1H), 7.25 (t, J = 8.0 Hz, 1H), 6.93 (s, 1H), 6.53 (d, J = 12.8 Hz, 2H), 4.68 (s, 2H), 3.99 - 3.95 (m, 2H), 3.82 (s, 1H), 3.67 - 3.64 (m, 3H), 3.41 - 3.34 (m, 5H), 3.29 - 3.16 (m, 1H), 2.70 - 2.60 (m, 3H), 2.45 - 2.43 (m, 5H), 2.15 - 2.12 (m, 1H), 2.03 - 2.00 (m, 1H), 1.90 - 1.87 (m, 1H), 1.46 - 1.35 (m, 4H)103 947.3 10.93 - 10.91 (m, 1H), 10.88 (s, 1H), 8.26 - 8.15 (m, 1H), 8.05 - 7.89 (m,1H), 7.76 - 7.74 (m, 3H), 7.71 (s, 1H), 7.67 - 7.57 (m, 3H), 7.32 (t, J = 9.6 Hz, 1H), 6.68 (s, 1H), 6.67 - 6.58 (m, 2H), 4.61 (t, J = 5.2 Hz, 2H), 4.06 (dd, J = 12.8, 5.2 Hz, 1H), 3.77 (s, 2H), 3.63 - 3.60 (m, 1H), 3.49 (s, 3H), 3.43 (t, J =5.2 Hz, 2H), 3.29 - 3.26 (m, 1H), 3.21 - 3.04 (m, 1H), 3.00 - 2.99 (m, 1H),WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+2.94 - 2.69 (m, 4H), 2.63 (s, 3H), 2.53 - 2.52 (m, 1H), 2.50 - 2.48 (m, 3H), 2.46 - 2.27 (m, 1H), 2.17 - 2.04 (m, 1H), 2.02 - 1.91 (m, 1H), 1.70 - 1.35 (m, 6H)104 947.3 10.93 (s, 1H), 10.87 (s, 1H), 8.43 - 8.22 (m, 1H), 8.15 (dd, J = 6.8, 2.8 Hz,1H), 8.05 - 7.92 (m, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.66 (d, J = 8.4 Hz, 2H), 7.64 (s, 1H), 7.32 (t, J = 9.6 Hz, 1H), 6.71 (s, 1H), 6.62 (d, J = 12.8 Hz, 2H), 4.77 - 4.55 (m, 2H), 4.11 - 3.98 (m, 2H), 3.91 - 3.81 (m, 1H), 3.80 - 3.64 (m, 3H), 3.49 (s, 3H), 3.46- 3.38 (m, 2H), 3.28 - 3.26 (m, 1H), 3.25 - 3.17 (m, 1H), 2.80 (d, J = 4.8 Hz, 3H), 2.76 - 2.70 (m, 2H), 2.69 - 2.66 (m, 1H), 2.63 (s, 3H), 2.55 -2.51 (m, 1H), 2.49 (s, 3H), 2.28 - 2.15 (m, 1H), 2.14 - 2.03 (m, 1H), 2.02 - 1.93 (m, 1H), 1.61 - 1.38 (m, 4H)105 900.3 11.31 (s, 1H), 10.86 (s, 1H), 8.40 (d, J = 9.2 Hz, 1H), 7.85 - 7.75 (m, 2H), 7.73- 7.58 (m, 4H), 6.75 (s, 1H), 6.14 - 6.06 (m, 2H), 4.83 - 4.67 (m, 2H), 4.03 (dd, J = 12.6, 5.2 Hz, 1H), 3.90 - 3.79 (m, 4H), 3.74 - 3.61 (m, 3H), 3.49 (s, 3H), 3.29 - 3.21 (m, 2H), 3.17 - 3.16 (m, 1H), 3.14 (dd, J = 10.4, 2.4 Hz, 1H), 2.84 - 2.71 (m, 2H), 2.69 - 2.58 (m, 6H), 2.51 - 2.50 (m, 1H), 2.49 - 2.44 (m, 3H), 2.23 - 2.00 (m, 5H), 1.95 – 1.93 (m, 1H)106 931.3 11.66 (s, 1H), 10.88 (s, 1H), 8.42 (d, J = 9.2 Hz, 1H), 8.37 (s, 1H), 7.85 - 7.79(m, 2H), 7.76 - 7.69 (m, 3H), 7.60 (d, J = 8.4 Hz, 1H), 7.41 (s, 1H), 7.02 (s, 1H), 7.00 (d, J = 1.6 Hz, 1H), 4.64 (t, J = 6.0 Hz, 2H), 4.33 (dd, J = 9.6, 5.2 Hz, 1H), 3.97 (s, 3H), 3.48 (s, 3H), 3.35 - 3.22 (s, 3H), 2.69 - 2.63 (m, 1H), 2.62 (s, 3H), 2.56 - 2.52 (m, 1H), 2.51 (s, 3H), 2.41 - 2.28 (m, 1H), 2.21 - 2.10 (m, 1H), 2.07 - 1.96 (m, 3H), 1.74 - 1.57 (m, 6H), 1.26 - 1.16 (m, 2H) 107 887.6 10.88 (s, 2H), 8.86 (d, J = 2.4 Hz, 1H), 8.14 (dd, J = 8.4, 2.4 Hz, 1H), 7.77 (d,J = 8.4 Hz, 2H), 7.66 - 7.64 (m, 3H), 7.28 (d, J = 8.4 Hz, 1H), 6.71 (s, 1H), 6.61 (d, J = 12.8 Hz, 2H), 4.65 - 4.63 (m, 2H), 4.03 - 4.01 (m, 2H), 3.84 - 3.83 (m, 1H), 3.91 - 3.64 (m, 3H), 3.25 - 2.97 (m, 3H), 2.72 - 2.70 (m, 4H), 2.63 (s, 3H), 2.57 - 2.29 (m, 3H), 2.28 - 2.01 (m, 3H), 2.09 - 2.07 (m, 3H), 2.00 - 1.90 (m, 1H), 1.54 - 1.38 (m, 4H)108 888.4 11.68 (s, 1H), 10.96 (s, 1H), 8.47 - 8.35 (m, 1H), 7.87- 7.77 (m, 3H), 7.76- 7.65 (m, 3H), 7.03 (d, J = 10.2 Hz, 2H), 6.85 (s, 1H), 4.71 - 4.69 (m, 2H), 4.29 -4.13 (m, 1H), 3.83 - 3.76 (m, 1H), 3.77 - 3.64 (m, 5H), 3.58 - 3.51 (m, 4H), 3.38 - 3.30 (m, 2H), 3.29 - 3.20 (m, 2H), 2.89 - 2.76 (m, 1H), 2.76 - 2.60 (m, 9H), 2.58 - 2.53 (m, 2H), 2.22 - 2.06 (m, 1H), 2.05 - 1.91 (m, 1H), 1.79 - 1.60 (m, 2H), 1.51 - 1.32 (m, 2H)109 900.3 8.64 (d, J = 9.2 Hz, 1H), 7.91 (s, 1H), 7.73 (d, J = 8.0 Hz, 2H), 7.64 - 7.58 (m,3H), 7.45 (d, J = 9.2 Hz, 1H), 6.63 (s, 1H), 5.94 (d, J = 10.4 Hz, 2H), 5.14 - 4.98 (m, 2H), 3.95 - 3.76 (m, 8H), 3.61 (s, 3H), 3.44 - 3.36 (m, 2H), 3.31 (t, J = 5.2 Hz, 2H), 2.83 - 2.62 (m, 10H), 2.50 (s, 3H), 2.46 - 2.39 (m, 2H), 2.39 - 2.25 (m, 3H), 2.18 - 2.09 (m, 1H)111 947.4 10.88 (s, 1H), 10.86 (s, 1H), 8.19 (dd, J = 6.4, 2.8 Hz, 1H), 7.99 - 7.96 (m,1H), 7.81 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 8.4 Hz, 2H), 7.63 (s, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.32 (t, J = 9.2 Hz, 2H), 6.14 (d, J = 10.8 Hz, 2H), 4.48 (t, J = 6.4 Hz, 2H), 4.03 (dd, J = 12.8, 4.8 Hz, 1H), 3.96 (t, J = 6.8 Hz, 2H), 3.84 - 3.80 (m, 2H), 3.72-3.64 (m, 1H), 3.49 (s, 3H), 3.35 (t, J = 5.6 Hz, 2H), 3.09 - 3.07 (m, 2H), 2.81 - 2.78 (m, 1H), 2.81 - 2.78 (m, 2H), 2.65 (s, 3H), 2.51 (s, 3H), 2.50 -2.48 (m, 2H), 2.19 (s, 3H), 2.10 - 1.94 (m, 2H), 1.41 - 1.35 (m, 2H), 1.07 - 0.98 (m, 2H)112 933.4 10.97 (s, 1H), 10.91 (s, 1H), 8.19 (dd, J = 6.4, 2.8 Hz, 1H), 8.01 - 7.92 (m,1H), 7.77 (d, J = 8.4 Hz, 2H), 7.74 - 7.64 (m, 4H), 7.62 (s, 1H), 7.31 (t, J = 9.6 Hz, 1H), 7.11 (d, J = 10.0 Hz, 2H), 6.70 (s, 1H), 4.61 (t, J = 4.8 Hz, 2H), 4.28 - 4.19 (m, 1H), 4.15 (t, J = 6.8 Hz, 2H), 3.83 - 3.70 (m, 3H), 3.48 (s, 3H), 3.42- 3.35 (m, 2H), 3.10 - 3.00 (m, 3H), 2.89 - 2.65 (m, 3H), 2.62 (s, 3H), 2.59 -WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+2.53 (m, 1H), 2.49 (s, 3H), 2.22 - 2.06 (m, 1H), 2.05 - 1.96 (m, 1H), 1.39 - 1.31 (m, 2H), 1.00 - 0.92 (m, 2H)113 947.4 10.88 (s, 2H), 8.18 (dd, J = 6.8, 2.8 Hz, 1H), 8.01 - 7.93 (m, 1H), 7.81 (d, J =8.0 Hz, 2H), 7.74 - 7.67 (m, 2H), 7.65 (s, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.30 (t, J = 9.6 Hz, 1H), 6.62 (d, J = 12.8 Hz, 2H), 4.61 - 4.45 (m, 2H), 4.10 - 3.98 (m, 2H), 3.91 - 3.81 (m, 1H), 3.79 - 3.65 (m, 3H), 3.49 (s, 3H), 3.46 - 3.42 (m, 1H), 3.32 - 3.20 (m, 4H), 2.85 - 2.68 (m, 3H), 2.66 (s, 3H), 2.51 (s, 3H), 2.18 (s, 3H), 2.27- 2.21 (m, 1H), 2.16 - 2.01 (m, 1H), 2.01 - 1.91 (m, 1H), 1.57 - 1.38 (m, 4H)114 859.4 11.28 (s, 1H), 10.95 (s, 1H), 8.42 (d, J = 8.8 Hz, 1H), 7.79 (d, J = 8.4 Hz, 2H),7.70 - 7.68 (m, 3H), 7.67 (s, 1H), 7.00 (d, J = 10.4 Hz, 2H), 6.75 (s, 1H), 4.70 (t, J = 5.2 Hz, 2H), 4.20 (dd, J = 12.8, 5.2 Hz, 1H), 3.48 (s, 3H), 3.34 - 3.21 (m, 3H), 2.81 - 2.76 (m, 1H), 2.65 (s, 3H), 2.61 (s, 3H), 2.60 - 2.58 (m, 2H), 2.55 - 2.50 (m, 1H), 2.50 (s, 3H), 2.49 - 2.40 (m, 1H), 2.13 (dd, J = 12.8, 3.2 Hz, 1H), 2.00 (s, 4H), 1.68 - 1.57 (m, 4H), 1.52 - 1.45 (m, 2H), 1.21 - 1.05 (m, 2H)115 859.4 11.23 (s, 1H), 10.95 (s, 1H), 8.45 (d, J = 8.8 Hz, 1H), 7.80 (d, J = 8.4 Hz, 2H),7.72 - 7.65 (m, 4H), 6.99 (d, J = 10.0 Hz, 2H), 6.76 (s, 1H), 4.76 (t, J = 5.2 Hz, 2H), 4.19 (dd, J = 12.8, 5.2 Hz, 1H), 3.55 - 3.48 (m, 1H), 3.49 (s, 3H), 3.21 (t, J = 5.2 Hz, 2H), 2.86 - 2.75 (m, 1H), 2.70 - 2.65 (m, 2H), 2.66 (s, 3H), 2.62 (s, 3H), 2.56 - 2.52 (m, 1H), 2.49 (s, 3H), 2.46 - 2.40 (m, 1H), 2.29 - 2.20 (m, 1H), 2.15 - 2.05 (m, 1H), 2.04 - 1.94 (m, 1H), 1.72 - 1.61 (m, 4H), 1.54 - 1.39 (m, 6H)116 895.3 11.29 (s, 1H), 10.88 (s, 1H), 8.43 (d, J = 9.2 Hz, 1H), 7.80 (d, J = 8.4 Hz, 2H),7.72 - 7.68 (m, 4H), 7.56 (d, J = 6.0 Hz, 1H), 7.47 (d, J = 10.8 Hz, 1H), 6.76 (s, 1H), 4.71 (t, J = 5.2 Hz, 2H), 4.32 (dd, J = 10.0, 4.8 Hz, 1H), 4.00 (s, 3H), 3.48 (s, 3H), 3.27 - 3.25 (m, 2H), 2.77 - 2.61 (m, 6H), 2.66 (s, 3H), 2.61 (s, 3H), 2.50 (s, 3H), 2.43 - 2.33 (m, 1H), 2.17 - 2.12 (m, 1H), 2.10 - 2.00 (m, 3H), 1.72 - 1.64 (m, 6H), 1.24 - 1.16 (m, 2H)117 906.2 11.33 (s, 1H), 10.85 (s, 1H), 8.41 (d, J = 9.2 Hz, 1H), 7.80 (d, J = 8.4 Hz, 2H),7.74 - 7.65 (m, 4H), 7.50 (d, J = 8.8 Hz, 1H), 6.90 (dd, J = 9.2, 2.0 Hz, 1H), 6.83 (s, 1H), 6.76 (s, 1H), 4.79 - 4.78 (m, 2H), 4.26 (dd, J = 9.2, 5.2 Hz, 1H), 4.07 - 3.98 (m, 1H), 3.91 - 3.89 (m, 4H), 3.88 - 3.72 (m, 2H), 3.69 (dd, J = 10.4, 6.4 Hz, 1H), 3.49 (s, 3H), 3.41 - 3.40 (m, 1H), 3.35 (s, 4H), 3.19 (dd, J = 10.2, 4.0 Hz, 1H), 2.66 - 2.62 (m, 10H), 2.57 (s, 1H), 2.34 - 2.26 (m, 1H), 2.16 - 2.14 (m, 2H), 1.56- 1.54 (m, 4H)118 906.3 11.31 (s, 1H), 10.84 (s, 1H), 8.42 (d, J = 9.2 Hz, 1H), 7.82 - 7.66 (m, 6H), 7.49(d, J = 9.2 Hz, 1H), 6.76 (s, 1H), 6.37 - 6.35 (m, 2H), 4.77 (t, J = 6.0 Hz, 2H), 4.24 (dd, J = 9.2, 5.2 Hz, 1H), 4.01 - 4.00 (m, 2H), 3.90 - 3.78 (m, 5H), 3.69 - 3.67 (m, 1H), 3.48 (s, 3H), 3.38 (d, J = 5.6 Hz, 2H), 3.23 - 3.22 (m, 1H), 3.09 - 3.08 (m, 1H), 2.98 - 2.97 (m, 2H), 2.89 - 2.81 (m, 1H), 2.63 - 2.60 (m, 7H), 2.56 - 2.55 (m, 1H), 2.49 (s, 3H), 2.30 - 2.28 (m, 1H), 2.15 - 2.13 (m, 1H), 1.56 - 1.21 (m, 2H), 0.98 - 0.94 (m, 2H)119 947.4 10.87 (s, 1H), 10.72 (s, 1H), 8.42 - 8.31 (m, 1H), 8.26 - 8.10 (m, 1H), 7.86 - 7.77 (m, 2H), 7.73 - 7.64 (m, 3H), 7.47 - 7.38 (m, 1H), 7.36 - 7.29 (m, 1H), 6.74 (s, 1H), 6.62 (d, J = 12.8 Hz, 2H), 4.86 - 4.75 (m, 2H), 4.14 - 3.98 (m, 2H), 3.88 - 3.84 (m, 1H), 3.79 - 3.66 (m, 3H), 3.49 (s, 3H), 3.40 - 3.34 (m, 6H), 3.23 - 3.16 (m, 1H), 2.86 - 2.77 (m, 4H), 2.77 - 2.67 (m, 2H), 2.64 (s, 3H), 2.53 - 2.52 (m, 1H), 2.28 - 2.16 (m, 1H), 2.16 - 2.03 (m, 1H), 2.01 - 1.92 (m, 1H), 1.58 - 1.33 (m, 4H).120 987.1 11.06 (s, 1H), 10.85 (s, 1H), 8.34 (s, 1H), 8.14 (dd, J = 6.4, 2.8 Hz, 1H), 7.97 - 7.94 (m, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.77 - 7.69 (m, 4H), 7.35 (t, J = 9.6 Hz, 1H), 7.01 (s, 1H), 6.13 (d, J = 11.2 Hz, 2H), 4.61 (t, J = 5.2 Hz, 2H), 4.03 (dd,J = 12.6, 5.2 Hz, 1H), 3.96 (t, J = 8.0 Hz, 2H), 3.81 (q, J = 6.9 Hz, 2H), 3.71 -WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+3.64 (m, 1H), 3.48 (s, 3H), 3.46 - 3.45 (m, 2H), 3.13 - 3.12 (m, 1H), 3.04 - 2.91 (m, 2H), 2.81 - 2.77 (m, 2H), 2.51 (s, 3H), 2.50 - 2.49 (m, 1H), 2.11 - 2.03 (m, 1H), 1.97 - 1.92 (m, 1H), 1.41 - 1.34 (m, 2H), 1.05 - 0.97 (m, 2H) 121 936.5 10.91 (s, 1H), 10.89 (s, 1H), 8.26 (s, 1H), 8.19 (dd, J = 6.4, 2.8 Hz, 1H), 8.02 - 7.94 (m, 1H), 7.82 - 7.77 (m, 2H), 7.71 - 7.65 (m, 2H), 7.66 - 7.58 (m, 2H), 7.42 (s, 1H), 7.38 - 7.29 (m, 1H), 7.01 (d, J = 8.4 Hz, 1H), 6.71 (s, 1H), 4.64 - 4.55 (m, 2H), 4.33 (dd, J = 9.6, 5.2 Hz, 1H), 3.97 (s, 3H), 3.48 (s, 3H), 3.31 - 3.21 (m, 3H), 2.80 (d, J = 4.6 Hz, 3H), 2.67 (s, 3H), 2.63 (s, 3H), 2.63 - 2.52 (m, 4H), 2.36 (s, 1H), 2.23 - 2.12 (m, 1H), 2.07 - 1.96 (m, 3H), 1.75 - 1.58 (m, 6H), 1.32 - 1.13 (m, 3H)122 940.6 10.88 (s, 1H), 10.87 (s, 1H), 8.21 (dd, J = 6.4, 2.4 Hz, 1H), 7.99 - 7.95 (m,1H), 7.78 (d, J = 8.4 Hz, 2H), 7.75 - 7.65 (m, 4H), 7.62 (s, 1H), 7.54 (d, J = 6.0 Hz, 1H), 7.46 (d, J = 10.8 Hz, 1H), 7.32 (t, J = 9.6 Hz, 1H), 6.70 (s, 1H), 4.57 (t, J = 5.6 Hz, 2H), 4.31 (dd, J = 10.0, 4.8 Hz, 1H), 3.99 (s, 3H), 3.46 (s, 3H), 3.25 (t, J = 6.0 Hz, 3H), 2.81 - 2.73 (m, 1H), 2.71 - 2.65 (m, 2H), 2.62 (s, 3H), 2.61 - 2.58 (m, 1H), 2.57 - 2.53 (m, 1H), 2.49 (s, 3H), 2.41 - 2.30 (m, 1H), 2.19 -2.10 (m, 1H), 2.09- 1.96 (m, 3H), 1.78 - 1.61 (m, 6H), 1.29 - 1.11 (m, 2H)123 1013.3 1H NMR (400 MHz, DMSO-d6) δ 11.05 – 10.69 (m, 3H), 8.23 - 8.14 (m,1H), 8.00 - 7.98 (m, 1H), 7.81 - 7.74 (m, 2H), 7.71 - 7.65 (m, 2H), 7.65 - 7.57 (m, 2H), 7.35 (t, J = 9.2 Hz, 1H), 6.71 (s, 1H), 6.58 (d, J = 2.4 Hz, 1H), 6.16 - 6.08 (m, 2H), 4.62 (t, J = 6.0 Hz, 2H), 4.03 (dd, J = 12.8, 5.2 Hz, 1H), 3.94 (t, J = 8.0 Hz, 2H), 3.81 (t, J = 6.8 Hz, 2H), 3.76 (s, 3H), 3.67 - 3.65 (m, 1H), 3.48 (s, 3H), 3.40 (t, J = 6.0 Hz, 2H), 3.27 (s, 2H), 3.09 - 3.08 (m, 1H), 2.97 - 2.96 (m, 2H), 2.84 - 2.71 (m, 2H), 2.63 (s, 3H), 2.49 (s, 3H), 2.14 - 2.00 (m, 1H), 1.99 - 1.89 (m, 1H), 1.44 - 1.29 (m, 2H), 1.06 - 0.97 (m, 2H) 125 919.3 10.84 - 10.83 (m, 1H), 10.71 (s, 1H), 8.22 - 8.10 (m, 1H), 7.86 - 7.75 (m,3H), 7.75 - 7.60 (m, 4H), 7.39 (s, 1H), 7.31 – 7.23 (m, 1H), 6.74 (m, 1H), 6.26 - 6.11 (m, 2H), 4.80 - 4.78 (m, 2H), 4.15 - 3.95 (m, 2H), 3.87 - 3.85 (m, 1H), 3.80 - 3.67 (m, 1H), 3.58 - 3.42 (m, 4H), 3.41 - 3.33 (m, 1H), 3.32 - 3.07 (m, 4H), 2.99 - 2.86 (m, 1H), 2.86 - 2.70 (m, 1H), 2.70 - 2.58 (m, 3H), 2.57 - 2.53 (m, 3H), 2.52 - 2.51 (m, 3H), 2.19 - 1.76 (m, 4H)126 919.3 10.92 (s, 1H), 10.84 (d, J = 2.8 Hz, 1H), 8.19 (dd, J = 6.6, 2.8 Hz, 1H), 8.01 - 7.91 (m, 1H), 7.78 (d, J = 8.0 Hz, 2H), 7.74 - 7.61 (m, 5H), 7.36 - 7.26 (m, 1H), 6.71 (s, 1H), 6.28 - 6.15 (m, 2H), 4.80 - 4.57 (m, 2H), 4.12 - 3.98 (m, 2H), 3.86 (d, J = 5.2 Hz, 1H), 3.76 - 3.63 (m, 1H), 3.61 - 3.53 (m, 1H), 3.48 (d, J = 2.4 Hz, 3H), 3.33 (s, 3H), 3.28 - 3.09 (m, 4H), 2.98 - 2.86 (m, 1H), 2.84 - 2.72 (m, 1H), 2.63 (d, J = 2.8 Hz, 3H), 2.54 (s, 1H), 2.50 (s, 3H), 2.15 - 1.83 (m, 4H)127 933.3 10.85 (s, 1H), 10.69 (s, 1H), 8.17 (t, J = 8.0 Hz, 1H), 7.82 (s, 1H), 7.78 (d, J =8.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.72 - 7.66 (m, 2H), 7.45 (t, J = 8.0 Hz, 1H), 7.32 (t, J = 8.0 Hz, 1H), 6.75 (s, 1H), 6.13 (d, J = 11.2 Hz, 2H), 4.78 (t, J = 5.6 Hz, 2H), 4.03 (dd, J = 12.8, 5.2 Hz, 1H), 3.99 - 3.91 (m, 2H), 3.81 (q, J = 6.4 Hz, 2H), 3.73 - 3.62 (m, 1H), 3.48 (s, 3H), 3.41 (t, J = 5.6 Hz, 2H), 3.25 - 2.70 (m, 6H), 2.64 (s, 3H), 2.51 (s, 3H), 2.50 - 2.49 (m, 1H), 2.14 - 2.00 (m, 1H), 1.98 - 1.89 (m, 1H), 1.50 - 1.22 (m, 2H), 1.09 - 0.87 (m, 2H)128 947.3 10.85 (s, 1H), 10.71 (s, 1H), 8.36 (q, J = 4.4 Hz, 1H), 8.17 (t, J = 7.2 Hz, 1H),7.78 (d, J = 8.0 Hz, 2H), 7.68 (d, J = 8.0 Hz, 2H),7.72 - 7.65 (m, 1H), 7.41 (t, J = 7.6 Hz, 1H), 7.32 (t, J = 8.0 Hz, 1H), 6.75 (s, 1H), 6.13 (d, J = 11.2 Hz, 2H), 4.79 (t, J = 5.2 Hz, 2H), 4.03 (dd, J = 12.8, 5.2 Hz, 1H), 3.98 - 3.91 (m, 2H), 3.81 (q, J = 6.4 Hz, 2H), 3.71 - 3.63 (m, 1H), 3.48 (s, 3H), 3.40 (t, J = 4.8 Hz, 2H), 3.21 -2.71 (m, 7H), 2.80 (d, J = 4.4 Hz, 2H), 2.63 (s, 3H), 2.51 (s, 3H), 2.50 - 2.49 (m, 1H), 2.14 - 2.00 (m, 1H), 1.97- 1.90 (m, 1H), 1.43 - 1.27 (m,2H), 1.08 - 0.93 (m, 2H)WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+129 976.5 11.07 (s, 1H), 10.88 (s, 1H), 8.35 (s, 1H), 8.16 (dd, J = 6.4, 2.8 Hz, 1H), 8.02 - 7.93 (m, 1H), 7.85 - 7.78 (m, 2H), 7.76 - 7.69 (m, 4H), 7.60 (d, J = 8.4 Hz, 1H), 7.40 (s, 1H), 7.36 (dd, J = 10.0, 8.8 Hz, 1H), 7.04 - 6.98 (m, 2H), 4.59 (t, J = 5.6 Hz, 2H), 4.32 (dd, J = 9.6, 5.2 Hz, 1H), 3.96 (s, 3H), 3.47 (s, 3H), 3.35 - 3.29 (m, 4H), 2.71 - 2.52 (m, 4H), 2.49 (s, 3H), 2.42 - 2.28 (m, 1H), 2.22 - 2.12 (m, 1H), 2.08 - 1.98 (m, 3H), 1.76 - 1.56 (m, 6H), 1.26 - 1.19 (m, 2H) 130 994.2 11.07 (s, 1H), 10.87 (s, 1H), 8.34 (s, 1H), 8.16 (dd, J = 6.4, 2.8 Hz, 1H), 8.02 - 7.93 (m, 1H), 7.85 - 7.78 (m, 2H), 7.75 - 7.69 (m, 4H), 7.53 (d, J = 6.0 Hz, 1H), 7.46 (d, J = 10.8 Hz, 1H), 7.36 (t, J = 9.6 Hz, 1H), 7.01 (s, 1H), 4.64 - 4.55 (m, 2H), 4.31 (dd, J = 10.0, 4.0 Hz, 1H), 3.99 (s, 3H), 3.47 (s, 3H), 3.34 - 3.29 (m, 2H), 2.83 - 2.56 (m, 5H), 2.48 (s, 3H), 2.41 - 2.31 (m, 1H), 2.18 - 2.09 (m, 1H), 2.10- 1.97 (m, 3H), 1.77 - 1.62 (m, 6H), 1.30 - 1.13 (m, 3H) 131 940.5 10.88 (s, 1H), 10.66 (s, 1H), 8.19 (m, 1H), 7.89 - 7.78 (m, 3H), 7.73 - 7.63 (m, 4H), 7.56 (d, J = 6.0 Hz, 1H), 7.49 - 7.43 (m, 2H), 7.33 (t, J = 8.0 Hz, 1H), 6.75 (s, 1H), 4.81 - 4.71 (m, 2H), 4.32 (dd, J = 10.0, 5.2 Hz, 1H), 4.00 (s, 3H), 3.48 (s, 3H), 3.31 - 3.08 (m, 5H), 2.82 - 2.56 (m, 8H), 2.41 - 2.32 (m, 1H), 2.20 - 2.02 (m, 4H), 1.71 (s, 6H), 1.30 - 1.11 (m, 3H)132 947.3 10.84 (s, 1H), 10.70 (s, 1H), 8.18 (q, J = 6.4 Hz, 1H), 7.83 (s, 1H), 7.78 (d, J =7.6 Hz, 2H), 7.69 (d, J = 7.6 Hz, 4H), 7.45 (t, J = 7.2 Hz, 1H), 7.32 (t, J = 8.0 Hz, 1H), 6.75 (s, 1H), 6.19 (dd, J = 12.0, 4.4 Hz, 2H), 4.79 (q, J = 4.4 Hz, 2H), 4.02 (dd, J = 16.4, 4.0 Hz, 1H), 3.48 (s, 3H), 3.46 - 3.33 (m, 4H), 3.32 - 3.12 (m, 6H), 3.11 - 2.95 (m, 3H), 2.79 - 2.77 (m, 1H), 2.64 (s, 3H), 2.49 (s, 3H), 2.12 - 2.01 (m, 2H), 1.99 - 1.88 (m, 2H), 1.49 - 1.39 (m, 1H), 1.38 - 1.29 (m, 1H), 1.14 - 0.89 (m, 2H)133 947.2 10.91 (d, J = 2.8 Hz, 1H), 10.84 (s, 1H), 8.19 (dd, J = 6.4, 2.8 Hz, 1H), 8.02 - 7.92 (m, 1H), 7.77 (d, J = 8.0 Hz, 2H), 7.74 - 7.65 (m, 4H), 7.63 (s, 1H), 7.31 (t, J = 9.6 Hz, 1H), 6.71 (s, 1H), 6.19 (dd, J = 12.0, 2.8 Hz, 2H), 4.64 - 4.62 (m, 2H), 4.01 (d, J = 12.4 Hz, 1H), 3.49 - 3.47 (m, 3H), 3.40 - 3.34 (m, 4H), 3.32 - 3.19 (m, 5H), 3.18 - 3.10 (m, 1H), 3.10 - 2.98 (m, 1H), 2.98 - 2.86 (m, 1H), 2.86 -2.71 (m, 1H), 2.62 (s, 3H), 2.53 - 2.51 (m, 1H), 2.48 (s, 3H), 2.15 -2.01 (m, 2H), 2.01 - 1.90 (m, 2H), 1.51 - 1.40 (m, 1H), 1.40 - 1.28 (m, 1H), 1.20 - 1.01 (m, 1H), 1.01 - 0.90 (m, 1H)134 1001.2 10.84 (s, 1H), 10.76 (s, 1H), 8.37 (s, 1H), 8.08 (t, J = 6.8 Hz, 1H), 7.85 (s, 1H),7.81 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.70 (s, 1H), 7.50 (t, J = 7.2 Hz, 1H), 7.34 (t, J = 8.0 Hz, 1H), 7.03 (s, 1H), 6.19 (dd, J = 12.0, 3.2 Hz, 2H), 4.79 - 4.69 (m, 2H), 4.07 - 3.97 (m, 1H), 3.56 - 3.49 (m, 2H), 3.49 (s, 3H), 3.42 - 3.34 (m, 2H), 3.32- 3.12 (m, 6H), 3.11 - 3.02 (m, 1H), 3.01 -2.91 (m, 1H), 2.84 - 2.72 (m, 1H), 2.55 - 2.52 (m, 1H), 2.48 (s, 1H), 2.15 - 2.01 (m, 2H), 2.00 - 1.89 (m, 2H), 1.54 - 1.43 (m, 1H), 1.42 - 1.32 (m, 1H), 1.16 - 0.93 (m, 2H)135 987.2 10.86 (s, 1H), 10.78 (s, 1H), 8.38 (s, 1H), 8.07 (t, J = 6.8 Hz, 1H), 7.85 (s, 1H),7.81 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.71 (s, 1H), 7.50 (t, J = 1.6 Hz, 1H), 7.34 (t, J = 8.0 Hz, 1H), 7.03 (s, 1H), 6.13 (d, J = 10.8 Hz, 2H), 4.73 (t, J = 5.2 Hz, 2H), 4.03 (dd, J = 12.8, 5.2 Hz, 1H), 3.95 (t, J = 8.0 Hz, 2H), 3.86 - 3.76 (m, 2H), 3.74 - 3.65 (m, 1H), 3.51 (t, J = 5.2 Hz, 2H), 3.49 (s, 3H), 3.29 - 3.20 (m, 1H), 3.19 - 3.13 (m, 1H), 3.06 - 2.94 (m, 2H), 2.89 - 2.73 (m, 2H), 2.55 - 2.52 (m, 1H), 2.48 (s, 3H), 2.14 - 2.02 (m, 1H), 1.99 - 1.89 (m, 1H), 1.48 - 1.32 (m, 2H), 1.12- 0.95 (m, 1H).136 973.2 10.84 (s, 1H), 10.79 (s, 1H), 8.37 (d, J = 3.6 Hz, 1H), 8.15 - 8.00 (m, 1H), 7.84- 7.81 (m, 3H), 7.72 (d, J = 8.4 Hz, 3H), 7.50 (t, J = 6.8 Hz, 1H), 7.32 (t, J = 8.0 Hz, 1H), 7.02 (s, 1H), 6.18 (dd, J = 12.0, 3.6 Hz, 2H), 4.85 - 4.70 (m, 2H), 4.19 - 4.09 (m, 1H), 4.05 - 3.99 (m, 1H), 3.95 - 3.90 (m, 1H), 3.80 - 3.70 (m,1H), 3.62 - 3.51 (m, 1H), 3.51 - 3.48 (m, 5H), 3.29 - 3.21 (m, 3H), 3.18 -WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+3.13 (m, 2H), 2.94 - 2.92 (m, 1H), 2.85 - 2.71 (m, 1H), 2.51 - 2.50 (m, 1H), 2.49 (s, 3H), 2.19 - 2.00 (m, 2H), 2.00 - 1.80 (m, 2H)137 973.2 11.07 (s, 1H), 10.84 (s, 1H), 8.35 (d, J = 2.4 Hz, 1H), 8.14 (dd, J = 6.0, 2.4 Hz,1H), 8.00 - 7.75 (m, 1H), 7.81 (d, J = 7.6 Hz, 2H), 7.74 - 7.71 (m, 4H), 7.34 (t, J = 9.2 Hz, 1H), 7.01 (s, 1H), 6.19 (dd, J = 12.4, 4.4 Hz, 2H), 4.73 - 4.62 (m, 2H), 4.15 - 3.95 (m, 2H), 3.94 - 3.85 (m, 1H), 3.80 - 3.69 (m, 1H), 3.62 - 3.52 (m, 1H), 3.50 - 3.47 (m, 4H), 3.42 - 3.40 (m, 1H), 3.27 - 3.25 (m, 1H), 3.21 - 3.10 (m, 4H), 2.93 (p, J = 7.6 Hz, 1H), 2.82 - 2.70 (m, 1H), 2.52 - 2.48 (m, 1H), 2.49 (s, 3H), 2.15 - 2.00 (m, 2H), 2.00 - 1.85 (m, 2H)138 936.4 10.87 (s, 2H), 8.21 (dd, J = 6.4, 2.8 Hz, 1H), 8.00 - 7.95 (m, 1H), 7.82 (d, J =8.0 Hz, 2H), 7.69 (s, 2H), 7.62 (s, 1H), 7.60 - 7.56 (m, 3H), 7.40 (s, 1H), 7.31 (t, J = 10.4 Hz, 1H), 7.00 (d, J = 8.4 Hz, 1H), 4.44 (t, J = 6.0 Hz, 2H), 4.32 (dd, J = 9.6, 4.8 Hz, 1H), 3.96 (s, 3H), 3.47 (s, 3H), 3.27 - 3.26 (m, 1H), 3.20 (t, J = 6.0 Hz, 2H), 2.67 - 2.60 (m, 7H), 2.51 - 2.50 (m, 1H), 2.49 (s, 3H), 2.40 - 2.30 (m, 1H), 2.18 - 2.04 (m, 4H), 2.03 - 2.00 (m, 3H), 1.72 - 1.63 (m, 6H), 1.23 - 1.22 (m, 2H)139 954.0 10.89 (s, 2H), 8.00 - 8.20 (m, 1H), 8.00 - 7.96 (m, 1H), 7.82 (d, J = 8.0 Hz,2H), 7.69 (s, 2H), 7.63 (s, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 6.0 Hz, 1H), 7.46 (d, J = 10.8 Hz, 1H), 7.32 (t, J = 9.4 Hz, 1H), 4.44 (t, J = 5.6 Hz, 2H), 4.33 - 4.30 (m, 1H), 3.99 (s, 3H), 3.47 (s, 3H), 3.32 - 3.25 (m, 1H), 3.20 (t, J = 5.6 Hz, 2H), 2.82 - 2.73 (m, 1H), 2.69 - 2.59 (m, 7H), 2.51 (s, 3H), 2.42 -2.34 (m, 1H), 2.18 - 2.11 (m, 4H), 2.07 - 2.01 (m, 3H), 1.72 - 1.64 (m, 6H), 1.23 - 1.21 (m, 2H)140 860.4 11.27 (s, 1H), 10.86 (s, 1H), 8.44 (d, J = 9.2 Hz, 1H), 7.81 - 7.76 (m, 2H), 7.72- 7.58 (m, 4H), 6.75 (s, 1H), 6.61 - 6.53 (m, 2H), 4.72 (t, J = 5.6 Hz, 2H), 4.03 (dd, J = 12.6, 5.2 Hz, 1H), 3.61 - 3.54 (m, 1H), 3.53 - 3.43 (m, 5H), 3.24 (t, J = 5.6 Hz, 2H), 3.23 - 3.21 (m, 3H), 3.11 - 3.08 (m, 3H), 2.85 - 2.72 (m, 3H), 2.72 - 2.64 (m, 3H), 2.60 (s, 3H), 2.18 (t, J = 6.4 Hz, 2H), 2.13 - 2.02 (m, 1H), 1.99 - 1.89 (m, 1H), 1.76 - 1.63 (m, 1H), 1.44 - 1.42 (m, 2H), 1.06 - 0.93 (m, 2H)141 976.3 10.88 (s, 1H), 10.73 (s, 1H), 8.37 (s, 1H), 8.13 - 8.08 (m, 1H), 7.86 - 7.80 (m,3H), 7.75 - 7.71 (m, 2H), 7.69 (s, 1H), 7.60 (d, J = 8.4 Hz, 1H), 7.54 - 7.48 (m, 1H), 7.41 (s, 1H), 7.34 (t, J = 8.0 Hz, 1H), 7.04 - 6.98 (m, 2H), 4.70 (t, J = 5.6 Hz, 2H), 4.36 - 4.30 (m, 1H), 3.97 (s, 3H), 3.47 (s, 3H), 3.32 - 3.29 (m, 3H), 2.73 - 2.59 (m, 4H), 2.59 - 2.54 (m, 1H), 2.50 (s, 3H), 2.40 - 2.29 (m, 1H), 2.22 -2.13 (m, 1H), 2.08 - 2.05 (m, 3H), 1.75 - 1.59 (m, 6H), 1.23 - 1.77 (m, 2H)142 919.6 10.87 (s, 1H), 10.71 - 10.69 (m, 1H), 8.22 - 8.12 (m, 1H), 7.83 (s, 1H), 7.77(d, J = 8.0 Hz, 2H), 7.74 - 7.57 (m, 4H), 7.45 (td, J = 9.2, 2.4 Hz, 1H), 7.32 (t, J = 8.0 Hz, 1H), 6.73 (d, J = 2.0 Hz, 1H), 6.22 - 6.03 (m, 2H), 4.79 - 4.76 (m, 2H), 4.13 - 3.87 (m, 3H), 3.87 - 3.72 (m, 2H), 3.64 - 3.60 (m, 1H), 3.56 - 3.40 (m, 4H), 3.32 - 3.25 (m, 3H),3.16 - 3.12 (m, 2H), 3.06 - 2.94 (m, 1H), 2.91 - 2.72 (m, 2H), 2.64 - 2.63 (m, 3H), 2.49 - 2.48 (m, 3H), 2.18 - 2.03 (m, 1H), 2.00 - 1.87 (m, 1H), 1.68 - 1.31 (m, 2H)143 947.4 10.88 (s, 1H), 10.71 - 10.68 (m, 1H), 8.19 (d, J = 8.0 Hz, 1H), 7.84 (s, 1H),7.77 (d, J = 8.4 Hz, 2H), 7.69 - 7.68 (m, 2H), 7.64 (d, J = 8.4 Hz, 2H), 7.45 (t, J = 7.0 Hz, 1H), 7.32 (t, J = 8.0 Hz, 1H), 6.72 (s, 1H), 6.64 (d, J = 12.8 Hz, 2H), 4.77 - 4.75 (m, 2H), 4.06 (dd, J = 12.8, 5.2 Hz, 1H), 3.79 - 3.76 (m, 2H), 3.63 - 3.60 (m, 1H), 3.49 - 3.48 (s, 3H), 3.44 (s, 1H), 3.38 - 3.37 (m, 1H), 3.18 - 3.15 (m, 1H), 3.01 - 2.98 (m, 1H), 2.77- 2.73 (m, 4H), 2.64 (s, 3H), 2.51 - 2.50 (m, 3H), 2.49 - 2.46 (m, 1H), 2.37 - 2.34 (m, 1H), 2.08 - 2.04 (m, 2H), 2.02 - 1.93 (m, 1H), 1.56 - 1.53 (m, 6H)144 895.4 11.28 (s, 1H), 10.91 (s, 1H), 8.43 (d, J = 9.2 Hz, 1H), 7.79 (d, J = 8.4 Hz, 2H),7.71 - 7.60 (m, 4H), 7.46 (d, J = 8.4 Hz, 1H), 7.05 (dd, J = 8.0, 5.6 Hz, 1H),WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+6.75 (s, 1H), 4.71 (t, J = 5.6 Hz, 2H), 4.36 (dd, J = 10.4, 5.2 Hz, 1H), 4.11 (s, 3H), 3.48 (s, 3H), 3.32 - 3.20 (m, 3H), 2.91 - 2.80 (m, 1H), 2.65 (s, 3H), 2.61 (s, 3H), 2.87 - 2.56 (m, 4H), 2.49 (s, 3H), 2.40 - 2.61(m, 1H), 2.23 - 2.12 (m, 1H), 2.09 - 1.99 (m, 3H), 1.73 - 1.60 (m, 6H), 1.25 - 1.11 (m, 2H)145 876.6 8.28 - 8.11 (m, 2H), 7.99- 7.91 (m, 1H), 7.77 (d, J = 8.4 Hz, 2H), 7.70 - 7.51(m, 3H), 7.31 (t, J = 9.6 Hz, 1H), 7.03 (d, J = 10.4 Hz, 2H), 6.70 (s, 1H), 4.59 (t, J = 5.6 Hz, 2H), 4.20 (dd, J = 12.8, 5.2 Hz, 1H), 3.63 - 3.58 (m, 1H), 3.48 (s, 3H), 3.48 - 3.42 (m, 1H), 3.34 (t, J = 7.2 Hz, 2H), 3.20 (t, J = 5.6 Hz, 2H), 2.86 (t, J = 6.8 Hz, 2H), 2.81 - 2.75 (m, 1H), 2.72 - 2.66 (m, 1H), 2.62 (s, 3H), 2.59 - 2.55 (m, 1H), 2.49 (s, 3H), 2.21 - 2.09 (m, 1H), 2.04 - 1.92 (m, 1H), 1.69 - 1.59 (m, 2H), 1.45 - 1.32 (m, 2H)147 936.4 10.88 (s, 1H), 10.70 - 10.63 (m, 1H), 8.35 (d, J = 5.2 Hz, 1H), 8.24 - 8.14 (m,2H), 7.82 - 7.77 (m, 2H), 7.72 - 7.65 (m, 3H), 7.59 (d, J = 8.4 Hz, 1H), 7.45 - 7.39 (m, 2H), 7.33 (t, J = 8.0 Hz, 1H), 7.01 (dd, J = 8.4, 2.0 Hz, 1H), 6.74 (s, 1H), 4.77 - 4.69 (m, 2H), 4.32 (dd, J = 9.6, 5.2 Hz, 1H), 3.97 (s, 3H), 3.47 (s, 3H), 3.26 - 3.14 (m, 3H), 2.79 (d, J = 4.4 Hz, 3H), 2.71 - 2.58 (m, 8H), 2.39 - 2.32 (m, 1H), 2.21 -2.11 (m, 1H), 2.10 - 1.98 (m, 3H), 1.76 - 1.58 (m, 6H), 1.33 - 1.17 (m, 4H)148 891.4 10.88 (s, 1H), 10.86 (s, 1H), 8.19 (dd, J = 6.4, 2.8 Hz, 1H), 7.99 - 7.96 (m,1H), 7.81 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 8.0 Hz, 2H), 7.63 (s, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.32 (t, J = 9.2 Hz, 2H), 6.14 (dd, J = 10.8, 0.8 Hz, 1H), 4.48 (t, J = 6.4 Hz, 2H), 4.03 (dd, J = 12.8, 4.8 Hz, 1H), 3.96 (t, J = 6.8 Hz, 2H), 3.84 - 3.80 (m, 2H), 3.72-3.64 (m, 1H), 3.49 (s, 3H), 3.35 (t, J = 5.6 Hz, 2H), 3.09 - 3.07 (m, 2H), 2.81 - 2.78 (m, 1H), 2.81 - 2.78 (m, 2H), 2.65 (s, 3H), 2.50 - 2.48 (m, 2H), 2.19 (s, 3H), 2.10 - 1.94 (m, 2H), 1.41 - 1.35 (m, 2H), 1.07- 0.98 (m, 2H)149 905.3 10.87 (s, 1H), 10.85 (s, 1H), 8.19 (dd, J = 6.4, 2.4 Hz, 1H), 8.01 - 7.92 (m,1H), 7.78 (d, J = 8.8 Hz, 2H), 7.76 - 7.69 (m, 2H), 7.67 (d, J = 8.4 Hz, 2H), 7.62 (s, 1H), 7.32 (t, J = 9.2 Hz, 1H), 6.69 (s, 1H), 6.59 (d, J = 12.8 Hz, 2H), 4.61 (t, J = 4.8 Hz, 2H), 4.05 (dd, J = 11.6, 4.4 Hz 1H), 3.55 - 3.51 (m, 1H), 3.48 (s, 3H), 3.22 (t, J = 5.2 Hz, 2H), 3.08 (t, J = 5.2 Hz, 4H), 2.83 - 2.72 (m, 1H), 2.62 (s, 3H), 2.53 - 2.51 (m, 1H), 2.49 (s, 3H), 2.41 - 2.36 (m, 1H), 2.14 (t, J = 4.8 Hz, 4H), 2.12- 2.02 (m, 1H), 2.00 – 1.91 (m, 1H), 1.79 - 1.68 (m, 2H), 1.57 - 1.44 (m, 2H)150 905.2 10.89 (s, 1H), 10.87 (s, 1H), 8.20 (dd, J = 6.4, 2.8 Hz, 1H), 8.06 - 7.90 (m,1H), 7.78 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H), 7.62 (s, 1H), 7.71 - 7.60 (m, 2H), 7.32 (t, J = 9.2 Hz, 1H), 6.70 (s, 1H), 6.60 (d, J = 12.4 Hz, 2H), 4.56 (t, J = 5.6 Hz, 2H), 4.05 (dd, J = 12.4, 4.8 Hz, 1H), 3.48 (s, 3H), 3.29 - 3.22 (m, 3H), 3.09 (s, 4H), 2.85 - 2.71 (m, 1H), 2.62 (s, 3H), 2.48 (s, 3H), 2.14 (s, 4H), 2.12 - 1.90 (m, 5H), 1.31 - 1.11 (m, 3H)151 904.3 10.95 (s, 1H), 10.65 (s, 1H), 8.21 - 8.17 (m, 2H), 7.87- 7.61 (m, 6H), 7.46- 7.44 (m, 1H), 7.32 (t, J = 8.0 Hz, 1H), 7.00 (d, J = 10.4 Hz, 2H), 6.73 (s, 1H), 4.72 (t, J = 5.6 Hz, 2H), 4.19 (dd, J = 12.4, 5.2 Hz, 1H), 3.48 (s, 3H), 3.26 (t, J = 5.6 Hz, 3H), 2.81 - 2.79 (m, 1H), 2.66 - 2.63 (m, 5H), 2.54 - 2.52 (m, 1H), 2.50 (s, 3H), 2.43 - 2.41 (m, 1H), 2.19 - 1.94 (m, 5H), 1.73 - 1.59 (m, 4H), 1.51 - 1.49 (m, 2H), 1.18 - 1.16 (m, 2H)152 956.3 12.22 (s, 1H), 10.92 (s, 1H), 10.86 (s, 1H), 8.59 (dd, J = 6.4, 2.0 Hz, 1H), 7.92- 7.83 (m, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.63 (s, 1H), 7.38 (t, J = 10.4 Hz, 1H), 7.27 (s, 1H), 7.11 (s, 1H), 6.71 (s, 1H), 6.12 (d, J = 11.2 Hz, 2H), 4.63 (t, J = 5.6 Hz, 2H), 4.03 (dd, J = 12.8, 5.2 Hz, 1H), 3.93 (t, J = 7.6 Hz, 2H), 3.79 (d, J = 5.6 Hz, 2H), 3.70 - 3.62 (m, 1H), 3.48 (s, 3H), 3.41 - 3.38 (m, 3H), 3.30 - 3.22 (m, 1H), 3.11 - 3.10 (m, 1H), 3.05 - 2.90 (m, 2H), 2.81 - 2.74 (m, 2H), 2.64 (s, 3H), 2.49 (s, 3H), 2.18 - 2.01 (m, 1H), 1.99- 1.88 (m, 1H), 1.50- 1.30 (m, 2H), 1.15 - 0.90 (m, 2H)WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+153 913.3 11.30 - 11.28 (m, 1H), 10.90 (s, 1H), 8.43 (d, J = 9.2 Hz, 1H), 7.84 - 7.77 (m,2H), 7.74 - 7.61 (m, 5H), 7.53 (s, 1H), 7.07 (d, J = 8.4 Hz, 1H), 6.77 (d, J = 6.0 Hz, 1H), 4.76 - 4.74 (m, 2H), 4.36 (dd, J = 10.0, 5.2 Hz, 1H), 3.99 (d, J = 4.8 Hz, 3H), 3.49 (d, J = 1.6 Hz, 3H), 3.27 - 3.26 (m, 4H), 2.84 - 2.83 (m, 1H), 2.65 - 2.63 (m, 9H), 2.50 (s, 3H), 2.42 - 2.33 (m, 1H), 2.28 - 1.98 (m, 6H), 1.78 - 1.77 (m, 3H), 1.20 - 1.13 (m, 1H)154 904.4 10.95 (s, 1H), 10.64 (s, 1H), 8.30 - 8.19 (m, 1H), 7.85 - 7.76 (m, 3H), 7.69 (d,J = 8.0 Hz, 4H), 7.50 - 7.41 (m, 1H), 7.33 (t, J = 8.0 Hz, 1H), 7.03 - 6.95 (m, 2H), 6.76 (s, 1H), 4.79 (t, J = 5.6 Hz, 2H), 4.23 - 4.14 (m, 1H), 3.49 (s, 4H), 3.23 (t, J = 5.6 Hz, 2H), 2.88 - 2.74 (m, 1H), 2.74 - 2.62 (m, 5H), 2.59 - 2.54 (m, 1H), 2.52 (s, 3H), 2.45 (s, 1H), 2.34 - 2.24 (m, 1H), 2.19 - 2.05 (m, 1H), 2.03 - 1.95 (m, 1H), 1.75 - 1.63 (m, 4H), 1.59 - 1.40 (m, 6H)155 919.2 10.86 (s, 1H), 10.71 (s, 1H), 8.34 (d, J = 5.2 Hz, 1H), 8.09 (td, J = 6.8, 1.6 Hz,1H), 7.87 (d, J = 5.2 Hz, 1H), 7.84 - 7.77 (m, 3H), 7.74 - 7.69 (m, 3H), 7.47 (td, J = 6.4, 1.6 Hz, 1H), 7.33 (t, J = 8.0 Hz, 1H), 6.86 (s, 1H), 6.14 (d, J = 10.8 Hz, 2H), 4.81 (t, J = 5.2 Hz, 2H), 4.04 (dd, J = 12.4, 5.2 Hz, 1H), 3.95 (t, J = 8.0 Hz, 2H), 3.81 (q, J = 6.0 Hz, 2H), 3.78 - 3.60 (m, 1H), 3.49 (s, 3H), 3.44 (t, J = 5.2 Hz, 2H), 3.22 - 3.19 (m, 2H), 3.18 - 2.88 (m, 2H), 2.88 - 2.71 (m, 2H), 2.52 (s, 3H), 2.52- 2.51 (m, 1H), 2.14 - 2.01 (m, 1H), 2.00 - 1.90 (m, 1H), 2.47 - 2.26 (m, 2H), 1.09 - 0.92 (m, 2H)156 876.4 10.97 (s, 1H), 10.64 (s, 1H), 8.23 - 8.14 (m, 1H), 7.85 - 7.75 (m, 3H), 7.68 (d,J = 8.0 Hz, 3H), 7.61 (s, 1H), 7.49 - 7.40 (m, 1H), 7.31 (t, J = 8.0 Hz, 1H), 7.05 (d, J = 10.4 Hz, 2H), 6.72 (s, 1H), 4.76 (d, J = 5.6 Hz, 2H), 4.28 - 4.19 (m, 1H), 3.51 - 3.47 (m, 4H), 3.31 - 3.20 (m, 6H), 2.89 - 2.76 (m, 3H), 2.63 - 2.51 (m, 4H), 2.50 - 2.47 (m, 3H), 2.22 - 2.09 (m, 1H), 2.06 - 1.98 (m, 1H), 1.94 - 1.87 (m, 2H), 1.18 - 1.06 (m, 2H)157 905.4 10.88 (s, 1H), 10.65 (s, 1H), 8.30 - 8.16 (m, 1H), 8.16 - 7.76 (m, 3H), 7.76- 7.53 (m, 4H), 7.53 - 7.38 (m, 1H), 7.33 (t, J = 7.6 Hz, 1H), 6.75 (s, 1H), 6.60 (d, J = 12.8 Hz, 2H), 4.99 - 4.59 (m, 2H), 4.06 (dd, J = 12.4, 5.2 Hz, 1H), 3.82 - 3.44 (m, 4H), 3.43 - 3.37 (m, 1H), 3.26 - 3.20 (m, 2H), 3.09 - 3.07 (m, 4H), 2.91 - 2.72 (m, 1H), 2.71 - 2.60 (m, 3H), 2.59 - 2.52 (m, 3H), 2.42 - 2.22 (m, 1H), 2.22 - 2.02 (m, 4H), 2.02 - 1.86 (m, 2H), 1.86 - 1.60 (m, 2H), 1.60 - 1.41 (m, 2H)158 905.3 10.88 (s, 1H), 10.66 (s, 1H), 8.24 - 8.15 (m, 1H), 7.85 - 7.76 (m, 3H), 7.73 - 7.66 (m, 4H), 7.50 - 7.42 (m, 1H), 7.33 (t, J = 8.0 Hz, 1H), 6.74 (s, 1H), 6.62 (d, J = 13.2 Hz, 2H), 4.74 (t, J = 5.6 Hz, 2H), 4.10 - 4.01 (m, 1H), 3.49 (s, 3H), 3.32 - 3.29 (m, 4H), 3.27 (t, J = 5.6 Hz, 2H), 3.10 (s, 3H), 2.85 - 2.72 (m, 1H), 2.64 (s, 3H), 2.55 - 2.51 (m, 3H), 2.21 - 1.96 (m, 8H), 1.25 - 1.18 (m, 2H) 159 876.3 10.95 (s, 1H), 10.66 (s, 1H), 8.29 - 8.13 (m, 1H), 7.84 (s, 1H), 7.81 - 7.74 (m,2H), 7.74 - 7.62 (m, 4H), 7.50 - 7.41 (m, 1H), 7.37 – 7.26 (m, 1H), 7.11 - 6.94 (m, 2H), 6.73 (s, 1H), 4.80 - 4.70 (m, 2H), 4.27 - 4.14 (m, 1H), 3.66 - 3.56 (m, 1H), 3.48 (s, 3H), 3.47 - 3.42 (m, 3H), 3.34 - 3.29 (m, 3H), 3.26 - 3.19 (m, 2H), 2.91 - 2.82 (m, 2H), 2.82 - 2.75 (m, 1H), 2.70 - 2.65 (m, 1H), 2.63 (s, 3H), 2.57- 2.53 (m, 1H), 2.19 - 2.05 (m, 1H), 2.04 - 1.93 (m, 1H), 1.71 - 1.59 (m, 2H), 1.44 - 1.30 (m, 2H)160 945.4 10.89 (s, 1H), 10.87 (s, 1H), 8.18 (dd, J = 6.4, 2.8 Hz, 1H), 8.00 - 7.92 (m,1H), 7.81 - 7.76 (m, 2H), 7.71 (d, J = 6.4 Hz, 2H), 7.68 - 7.62 (m, 3H), 7.35 - 7.27 (m, 1H), 6.70 (s, 1H), 6.17 - 6.04 (m, 2H), 4.65 - 4.63 (m, 2H), 4.03 (dd, J = 12.6, 5.2 Hz, 1H), 3.89 - 3.79 (m, 4H), 3.74 - 3.63 (m, 3H), 3.48 (s, 3H), 3.28 - 3.08 (m, 3H), 2.85 - 2.78 (m, 1H), 2.77 - 2.72 (m, 1H), 2.71 - 2.63 (m, 2H), 2.56 -2.52 (m, 3H), 2.50- 2.41 (m, 4H), 2.27 -2.11 (m, 4H), 2.11 - 2.02 (m, 1H)161 945.2 10.86 (s, 1H), 10.69 (s, 1H), 8.22 - 8.10 (m, 1H), 7.86 - 7.75 (m, 3H), 7.75 -7.53 (m, 4H), 7.41 (s, 1H), 7.31 (t, J = 7.6 Hz, 1H), 6.74 (s, 1H), 6.10 (d, J =WSGR Docket No. 66412-753.601Ex. LCMS ¹H NMR (400 MHz, DMSO-d6) δ(ESI+) m / z(M+H)+11.2 Hz, 2H), 4.86 - 4.70 (m, 2H), 4.03 (dd, J = 12.4, 5.2 Hz, 1H), 3.93 - 3.78 (m, 4H), 3.74 - 3.63 (m, 3H), 3.49 (s, 3H), 3.40 - 3.35 (m, 1H), 3.31 - 3.28 (m, 2H), 3.28 - 3.24 (m, 1H), 3.22 - 3.13 (m, 1H), 2.86 - 2.69 (m, 2H), 2.69 - 2.59 (m, 3H), 2.57 - 2.52 (m, 3H), 2.26 - 2.00 (m, 5H), 2.00 - 1.89 (m, 1H) 162 947.5 10.86 (s, 1H), 10.69 (s, 1H), 8.19 (t, J = 7.2 Hz, 1H), 7.83 - 7.82 (m, 3H), 7.70(s, 2H), 7.58 (d, J = 8.4 Hz, 2H), 7.45 - 7.42 (m, 1H), 7.31 (t, J = 8 Hz, 1H), 6.14 (d, J = 11.2 Hz, 1H), 4.65 (t, J = 5.6 Hz, 2H)...

Claims

WSGR Docket No. 66412-753.601CLAIMS WHAT IS CLAIMED IS:

1. A compound of Formula (I), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:Formula (I);wherein:R30is hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, or -L- heterocycloalkyl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”;R31is hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl, and heterocycloalkyl is independently optionally substituted with one or more R”;X is -O-, -S-, -NR32-, or -C(R33)2-;R32is hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, or -L- heterocycloalkyl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”;each R33is independently hydrogen, halogen, -CN, -NO2, -OH, -ORa, -SF5, -SH, -SRa, -NRcRd, Ci- Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”;each Z is independently N or CR2;each R2is independently hydrogen, halogen, -CN, or Ci-Cealkyl independently optionally substituted with one or more R’;- is a single or a double bond;WSGR Docket No. 66412-753.601U is N or C;T is N or C; provided that U and T are not both N;Y1is N, C, or CR3;R3is hydrogen, halogen, -CN, or Ci-Cealkyl independently optionally substituted with one or more R’; Y2is N, NRY2, CR4, C(R4)2, or C(=O);each R4is independently hydrogen, halogen, -CN, or Ci-Cealkyl independently optionally substituted with one or more R’;RY2is hydrogen or Ci-Cealkyl independently optionally substituted with one or more R;Y3is N or C;X1is N or CR5;R5is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, or Ci-Cealkyl independently optionally substituted with one or more R’;X2is N or CR6;R6is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, or Ci-Cealkyl independently optionally substituted with one or more R’;X3is N or CR7;R7is hydrogen, halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, or Ci-Cealkyl is independently optionally substituted with one or more R’;Ring A is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;each R8is independently halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, -C(=O)ORb, -C(=O)NRcRd, Ci- Cealkyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”; and / or two R8on the same atom are taken together to form an oxo;m is 0, 1, 2, 3, or 4;each L1is independently -O-, -S-, -S(=O)-, -S(=O)2-, -NR9-, -C(=O)-, Ci-Cioalkylene, Ci- Cioheteroalkylene, C2-Cealkenylene, C2-Cealkynylene, cycloalkylene, heterocycloalkylene, arylene, or heteroarylene; wherein each alkylene, alkenylene, alkynylene, and heteroalkylene is independently optionally substituted with one or more R’ and wherein each cycloalkylene, heterocycloalkylene, arylene, and heteroarylene is independently optionally substituted with one or more R”;each R9is independently hydrogen or Ci-Cealkyl independently optionally substituted with one or more R’;s is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;| — M’ is an E3 ubiquitin ligase targeting agent;each Rais independently Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L-cycloalkyl, -L- heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”;WSGR Docket No. 66412-753.601each Rbis independently hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, -L- cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”; each Rcand Rdare independently hydrogen, Ci-Cealkyl, Ci-Ceheteroalkyl, C2-Cealkenyl, C2-Cealkynyl, - L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl, heteroalkyl, alkenyl, and alkynyl is independently optionally substituted with one or more R’ and each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”; or Rcand Rdare taken together with the atom to which they are attached to form a heterocycloalkyl independently optionally substituted with one or more R”;L is absent or Ci-Csalkylene optionally substituted with one or more R’; andeach R’ is independently halogen, -CN, -OH, -OCi-Csalkyl, -S(=O)Ci-C3alkyl, -S(=O)2Ci-C3alkyl, -S(=O)2NH2, -S(=O)2NHCi-C3alkyl, -S(=O)2N(Ci-C3alkyl)2, -NH2, -NHCi-C3alkyl, -N(Ci-C3alkyl)2, - NHC(=O)OCi-C3alkyl, -C(=O)Ci-C3alkyl, -C(=O)OH, -C(=O)OCi-C3alkyl, -C(=O)NH2, - C(=O)N(Ci-C3alkyl)2, or -C(=O)NHCi-C3alkyl; wherein each alkyl is independently optionally substituted with one or more halogen;and / or two R’ on the same atom are taken together to form an oxo; andeach R” is independently halogen, -CN, -OH, -OCi-Csalkyl, -S(=O)Ci-C3alkyl, -S(=O)2Ci-C3alkyl, -S(=O)2NH2, -S(=O)2NHCi-C3alkyl, -S(=O)2N(Ci-C3alkyl)2, -NH2, -NHCi-C3alkyl, -N(Ci-C3alkyl)2, - NHC(=O)OCi-C3alkyl, -C(=O)Ci-C3alkyl, -C(=O)OH, -C(=O)OCi-C3alkyl, -C(=O)NH2, - C(=O)N(Ci-C3alkyl)2, -C(=O)NHCi-C3alkyl, Ci-C3alkyl, Ci-C3heteroalkyl, Ci-C6cycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more halogen;and / or two R” on the same atom are taken together to form an oxo.

2. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:

3. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:

4. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:WSGR Docket No. 66412-753.6015. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:

6. The compound of any one of claims 1-5, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:X is -O-.

7. The compound of any one of claims 1-6, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:R30is hydrogen, Ci-Cealkyl, -L-cycloalkyl, or -L-heterocycloalkyl.

8. The compound of any one of claims 1-7, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:R30is Ci-C6alkyl.

9. The compound of any one of claims 1-8, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:R31is hydrogen, halogen, -CN, Ci-Cealkyl, -L-cycloalkyl, or -L-heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more R’.

10. The compound of any one of claims 1-9, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:R31is Ci-C6alkyl.

11. The compound of any one of claims 1-10, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:O12. The compound of any one of claims 1-11, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each Z is independently CR2.

13. The compound of any one of claims 1-11, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:one Z is N and the remaining Z are independently CR2.

14. The compound of any one of claims 1-12, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:WSGR Docket No. 66412-753.601R215. The compound of any one of claims 1-12, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:R216. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein the compound is of Formula (la):

17. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein the compound is of Formula (lb):

18. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein the compound is of Formula (Ic):Formula (Ic).

19. The compound of any one of claims 1-18, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:X3is N.WSGR Docket No. 66412-753.60120. The compound of any one of claims 1-18, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:X3is CR7.

21. The compound of any one of claims 1-20, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each R4is independently hydrogen, halogen, or Ci-Cealkyl.

22. The compound of any one of claims 1-21, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each R4is independently hydrogen.

23. The compound of any one of claims 1-22, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:R6is hydrogen, halogen, or Ci-Cealkyl independently optionally substituted with one or more R’.

24. The compound of any one of claims 1-23, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:R6is hydrogen or Ci-Cealkyl.

25. The compound of any one of claims 1-24, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:R6is hydrogen.

26. The compound of any one of claims 1-25, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:R6is Ci-Cealkyl.

27. The compound of any one of claims 1-26, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:R7is hydrogen, halogen, or Ci-Cealkyl is independently optionally substituted with one or more R’.

28. The compound of any one of claims 1-27, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:R7is hydrogen or Ci-Cealkyl.

29. The compound of any one of claims 1-28, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:R7is hydrogen.

30. The compound of any one of claims 1-29, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:Ring A is phenyl or 5- or 6-membered heteroaryl.

31. The compound of any one of claims 1-30, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:Ring A is phenyl.WSGR Docket No. 66412-753.60132. The compound of any one of claims 1-30, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:Ring A is pyridinyl.

33. The compound of any one of claims 1-32, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each R8is independently halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)NRcRd, or Ci-Cealkyl independently optionally substituted with one or more R’.

34. The compound of any one of claims 1-32, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each R8is independently halogen, -CN, -ORa, -C(=O)NRcRd, or Ci-Cealkyl.

35. The compound of any one of claims 1-32, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each R8is independently halogen, -C(=O)NRcRd, or Ci-Cealkyl.

36. The compound of any one of claims 1-32, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each R8is independently halogen or Ci-Cealkyl37. The compound of any one of claims 1-32, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each R8is independently halogen or -C(=O)NRcRd.

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

39. The compound of any one of claims 1-38, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:m is 1, 2, or 3.

40. The compound of any one of claims 1-39, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:m is 1 or 2.

41. The compound of any one of claims 1-30, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:wherein:Ring C is cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;R8ais hydrogen, halogen, -CN, Ci-Cealkyl, or Ci-Cehaloalkyl;WSGR Docket No. 66412-753.601each R” is independently halogen, -CN, -OH, -OCi-C3alkyl, -S(=O)Ci-C3alkyl, - S(=O)2Ci-C3alkyl, -S(=O)2NH2, -S(=O)2NHCi-C3alkyl, -S(=O)2N(Ci-C3alkyl)2, -NH2, - NHCi-C3alkyl, -N(Ci-C3alkyl)2, -NHC(=O)OCi-C3alkyl, -C(=O)Ci-C3alkyl, -C(=O)OH, - C(=O)OCi-C3alkyl, -C(=O)NH2, -C(=O)N(Ci-C3alkyl)2, -C(=O)NHCi-C3alkyl, Ci-C3alkyl, Ci-C3heteroalkyl, Ci-Cecycloalkyl, or 3- to 6-membered heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more halogen;and / or two R” on the same atom are taken together to form an oxo; andu is 0, 1, 2, 3, or 4.

42. The compound of claim 41, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:

43. The compound of claim 41, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:

44. The compound of any one of claims 41-43, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:Ring C is a 5 -membered heteroaryl comprising one or two heteroatoms selected from the group consisting of N, O, and S.

45. The compound of any one of claims 41-44, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:Ring C is a 5-membered heteroaryl comprising one or two heteroatoms that are N.

46. The compound of any one of claims 41-45, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:u is 1.

47. The compound of any one of claims 41-46, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:R8ais halogen.

48. The compound of any one of claims 1-30, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:WSGR Docket No. 66412-753.60149. The compound of any one of claims 1-30, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:

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

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

52. The compound of any one of claims 1-51, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each L1is independently -O-, -NR9-, -C(=O)-, Ci-Cioalkylene, Ci-Cioheteroalkylene, cycloalkylene, or heterocycloalkylene; wherein each alkylene and heteroalkylene is independently optionally substituted with one or more R’ and wherein each cycloalkylene and heterocycloalkylene is independently optionally substituted with one or more R”.

53. The compound of any one of claims 1-51, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each L1is independently -O-, -NR9-, -C(=O)-, Ci-Cioalkylene, Ci-Cioheteroalkylene, cycloalkylene, or heterocycloalkylene.

54. The compound of any one of claims 1-51, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each L1is independently -O-, Ci-Cioalkylene, Ci-Cioheteroalkylene, cycloalkylene, or heterocycloalkylene.

55. The compound of any one of claims 1-51, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each L1is independently -O-, -C(=O)-, Ci-Cioalkylene, or heterocycloalkylene; or each L1is independently -O-, Ci-Cioalkylene, Ci-Cioheteroalkylene, or heterocycloalkylene; or each L1is independently -O-, Ci-Cioalkylene, or heterocycloalkylene; oreach L1is independently Ci-Cioalkylene or heterocycloalkylene; oreach L1is independently Ci-Cioalkylene, cycloalkylene, or heterocycloalkylene; or each L1is independently -O-, cycloalkylene, or heterocycloalkylene; orWSGR Docket No. 66412-753.601each L1is independently -O-, C1-C10alkylene, cycloalkylene, or heterocycloalkylene.

56. The compound of any one of claims 1-51, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each L1is independently -O-, -C(=O)-, Ci-C4alkylene, or heterocycloalkylene; oreach L1is independently -O-, Ci-C4alkylene, Ci-C4heteroalkylene, or heterocycloalkylene; or each L1is independently -O-, Ci-C4alkylene, or heterocycloalkylene; oreach L1is independently Ci-C4alkylene or heterocycloalkylene; oreach L1is independently Ci-C4alkylene, cycloalkylene, or heterocycloalkylene; oreach L1is independently -O-, cycloalkylene, or heterocycloalkylene; oreach L1is independently -O-, Ci-C4alkylene, cycloalkylene, or heterocycloalkylene.

57. The compound of any one of claims 1-51, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each L1is independently -O-, -C(=O)-, Ci-C4alkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N; oreach L1is independently -O-, Ci-C4alkylene, Ci-C4heteroalkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N; oreach L1is independently -O-, Ci-C4alkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N; oreach L1is independently Ci-C4alkylene or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N; oreach L1is independently C1-C4alkylene, C3-C6cycloalkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N; oreach L1is independently -O-, C3-C6cycloalkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N; oreach L1is independently -O-, C1-C4alkylene, C3-C6cycloalkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms that are N.

58. The compound of any one of claims 1-51, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each L1is independently -O-, -C(=O)-, Ci-C4alkylene, or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N.

59. The compound of any one of claims 1-51, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each L1is independently -O-, -C(=O)-, Ci-C4alkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms one or two heteroatoms that are N.

60. The compound of any one of claims 1-51, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:WSGR Docket No. 66412-753.601each L1is independently -O-, C1-C4alkylene, C3-C6cycloalkylene, or 3-to 12-membered heterocycloalkylene comprising one or two heteroatoms selected from the group consisting of O, S, and N.

61. The compound of any one of claims 1 -51, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each L1is independently -O-, C1-C4alkylene, C3-C6cycloalkylene, or 4-to 6-membered heterocycloalkylene comprising one or two heteroatoms one or two heteroatoms that are N.

62. The compound of any one of claims 1-61, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:s is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.

63. The compound of any one of claims 1-62, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:s is 1, 2, 3, 4, 5, or 6.

64. The compound of any one of claims 1-63, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:s is 1, 2, 3, or 4.

65. The compound of any one of claims 1-64, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:s is 4 or 5.

66. The compound of any one of claims 1-65, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:(R10)tI| — (BJ-W— XUM’ isuFormula (A);wherein:Y is CH, CD, C(CH3), C(CD3), or N;W is absent, -O-, -NRb-, or -C(=O)NRC-;Ring B is absent, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;each R10is independently halogen, -CN, -OH, -ORa, -NRcRd, -C(=O)Ra, -C(=O)ORb, - C(=O)NRcRd, Ci-Cealkyl, -L-cycloalkyl, -L-heterocycloalkyl, -L-aryl, or -L-heteroaryl; wherein each alkyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R”;and / or two R10on the same atom are taken together to form an oxo; andt is 0, 1, 2, 3, 4, 5, or 6.

67. The compound of claim 66, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:WSGR Docket No. 66412-753.601Y is CH.

68. The compound of claim 66, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:Y is N.

69. The compound of any one of claims 66-68, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:W is absent.

70. The compound of any one of claims 66-69, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:Ring B is absent.

71. The compound of any one of claims 66-70, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:Ring B is heterocycloalkyl.

72. The compound of any one of claims 66-70, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:Ring B is aryl or heteroaryl.

73. The compound of any one of claims 66-72, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each R10is independently halogen, -CN, -OH, -ORa, -NRcRd, Ci-Cealkyl, -L-cycloalkyl, or -L- heterocycloalkyl; wherein each alkyl is independently optionally substituted with one or more R’ and wherein each cycloalkyl and heterocycloalkyl is independently optionally substituted with one or more R”; and / or two R10on the same atom are taken together to form an oxo.

74. The compound of any one of claims 66-73, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:each R10is independently halogen, -ORa, Ci-Cealkyl; and / or two R10on the same atom are taken together to form an oxo.

75. The compound of any one of claims 66-72, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:two R10on the same atom are taken together to form an oxo.

76. The compound of any one of claims 66-75, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:t is 2, 3, 4, 5, or 6.

77. The compound of any one of claims 1-76, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:WSGR Docket No. 66412-753.6010 0 o78. The compound of any one of claims 1-76, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:

79. The compound of any one of claims 1-76, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:F80. The compound of any one of claims 1-76, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:F81. The compound of any one of claims 1-76, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:F82. A compound selected from a compound found in table 1 or in the specification, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

83. A pharmaceutical composition comprising a compound of any one of claims 1-82, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, and a pharmaceutically acceptable excipient.

84. A method of treating a disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of any one of claims 1-82, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, or the pharmaceutical composition of claim 83.WSGR Docket No. 66412-753.60185. The method of claim 84, wherein the disorder is alopecia, aspergillus, asthma, atomic dermatitis, chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis with nasal polyposis, gastritis, inflammatory bowel disease, pemphigoid, prurigo nodularis, sinusitis, or urticaria.

86. A method of degrading STAT6 in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of any one of claims 1-82, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, or the pharmaceutical composition of claim 83.

87. The method of claim 86, wherein the subject has alopecia, aspergillus, asthma, atomic dermatitis, chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis with nasal polyposis, gastritis, inflammatory bowel disease, pemphigoid, prurigo nodularis, sinusitis, or urticaria.

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